Chapter 199. Photosensitivity

A 50-year-old woman presented to the clinic with an abrupt onset of an intensely pruritic rash that extended over the dorsal aspect of both arms (Figure 199-1). The patient notes no new medicines and no recent exposures to any new chemicals. She acknowledged recent time spent outside in the sun. The plaques were photodistributed, with sparing of her watch area. A clinical diagnosis of polymorphous light eruption (PMLE) was made, and the patient was started on oral antihistamines and topical steroids. It was recommended that she minimize her sun exposure.

Photosensitivity is an abnormal skin response to ultraviolet light that occurs on sun-exposed areas of the skin. There are three common types of photodermatitis:

• PMLE (Figures 199-1 and 199-2).
• Phototoxic eruptions (Figures 199-3, 199-4, 199-5, 199-6, and 199-7).
• Photoallergic eruptions (Figure 199-8). Table 199-1 compares key characteristics of phototoxic and photoallergic reactions.

UV light radiating from the sun may be categorized into UVA (wavelength 320 to 400 nm), UVB (290 to 320 nm), and UVC (200 to 290 nm). UVC is completely absorbed by the earth's ozone layer and thus does not play a role in photosensitivity. Photosensitivity may be induced by UVA, UVB, or visible light (400 to 760 nm). Longer wavelength light penetrates deeper into the skin. UVA penetrates through to the dermis, but UVB mainly penetrates and affects the epidermis.

Ultraviolet light has multiple effects on the skin. Notably, it causes DNA damage and has immunosuppressive effects on skin inflammatory cells increasing the risk of carcinogenesis. In patients with photosensitivity, it elicits an inflammatory response in the skin, leading to the development of a photodermatosis.

• PMLE (Figures 199-1 and 199-2) may affect up to 10% of the population, with a predilection for females.1 The prevalence increases in northern latitudes. Onset typically occurs within the first three decades of life, but may appear spontaneously at any age.
• The incidence of drug- and plant-induced phototoxic reactions in the United States is unknown. Phototoxic reactions are much more common than photoallergic reactions.

PMLE is an idiopathic, delayed-type hypersensitivity reaction to UVA light and, to a lesser extent, UVB light (Figures 199-1 and 199-2). PMLE is the most common photoeruption encountered in clinical practice. The reaction will remit spontaneously with time and absence of sun exposure, but occasionally it will last as long as sun exposure occurs. PMLE usually begins in the first three decades of life and occurs more commonly in women. The rash develops within hours to days after exposure to sunlight and lasts for several days to a week.

There is a broad range of degrees of photosensitivity with PMLE. Extremely sensitive individuals can tolerate only minutes of exposure, whereas many people have a low sensitivity and require prolonged ­exposure to sunlight before developing a reaction. It is a recurrent condition that persists for many years in most patients.2

Phototoxic reactions are the most common drug-induced photoeruptions (Figures 199-3, 199-4, 199-5, 199-6, and 199-7). They are caused by absorption of ultraviolet rays by the causative drug, which releases energy and damages cell membranes, or, in the case of psoralens, DNA. The drugs that most frequently cause phototoxic reactions are NSAIDs, quinolones, tetracyclines, amiodarone, and the phenothiazines3 (Table 199-2). Most of these drugs have at least one resonating double bond or an aromatic ring that can absorb radiant energy. Most compounds are activated by wavelengths within the UVA (320 to 400 nm) range, although some compounds have a peak absorption within the UVB or visible range.

Phytophotodermatitis are phototoxic reactions to psoralens, which are plant compounds found in limes, celery, figs, and certain drugs. They can cause dramatic inflammation and bullae where the psoralen comes into contact with the skin (Figures 199-5, 199-6, and 199-7). The inflammation is frequently followed by hyperpigmentation.

Photoallergic eruptions are a lymphocyte-mediated reaction. Photoactivation of a drug or agent results in the development of a metabolite that can bind to proteins in the skin to form a complete antigen. The antigen is presented to lymphocytes by Langerhans cells, causing an inflammatory response and spongiotic dermatitis (eczema). The eruption is characterized by widespread eczema in the photodistribution areas such as the face, upper chest, arms, and back of hands (Figure 199-8). Most photoallergic reactions are caused by topical agents such as antibiotics and halogenated phenolic compounds added to soaps and fragrances.4 Systemic photoallergens such as the phenothiazines, chlorpromazine, sulfa products, and NSAIDs can produce photoallergic reactions, although most of their photosensitive reactions are phototoxic (Table 199-3).

Unprotected exposure to sunlight and the use of drugs associated with phototoxic and photoallergic eruptions are the main risk factors.

Clinical Features

Most cases of photodermatitis can be diagnosed on the basis of the patient's history. Be sure to review the patient's medications for possible sources.

• The appearance of the PMLE varies from person to person but is consistent in a given patient. Erythematous pruritic papules, sometimes with vesicles, are most common (Figures 199-1 and 199-2). Lesions may coalesce to form plaques. The rash typically involves the V of the neck and the arms, legs, or both. The face, which is exposed to sunlight in both summer and winter, tends to be spared. It tends to present in spring/summer, with the first significant UV exposure of the year. The rash typically develops 1 to 4 days after sun exposure.
• Phototoxic reaction occurs 2 to 6 hours after exposure to sunlight. The eruption typically appears as an exaggerated sunburn, with mild cases causing slight erythema and severe cases causing vesicles or bullae (Figures 199-3, 199-4, 199-5, 199-6, and 199-7).
• Phytophotodermatitis reactions are asymmetric and localized to the area in which the plant psoralen was in contact with the skin. Accompanying hyperpigmentation is a good clue to a phytophotodermatitis reaction (Figures 199-5, 199-6, and 199-7). Ask the patient if he or she had any contact with limes, celery, or figs. Squeezing lime juice into drinks is a particularly common cause of this reaction.
• Photoonycholysis phototoxicity reactions (sun-induced separation of the nail plate from the nail bed) have been reported with the use of tetracycline, psoralen, chloramphenicol, fluoroquinolones, oral contraceptives, quinine, and mercaptopurine. Photoonycholysis may be the only manifestation of phototoxicity in individuals with heavily pigmented skin.
• Photoallergic eruptions are characterized by widespread eczema in the photodistribution areas such as the face, upper chest, arms, and back of hands. They resemble allergic contact dermatitis, but the distribution is mostly limited to sun-exposed areas of the body (Figure 199-8).

Typical Distribution

• All photodermatitis reactions occur in sun-exposed areas, such as the face, ears, dorsal forearms, and V-area of the neck and upper chest.

Laboratory Testing

• Laboratory studies that may be helpful include antinuclear antibody (ANA), anti-Ro (SSA), and anti-La (SSB) titers to rule out lupus and porphyrin studies to exclude porphyria.
• Phototesting can be used to determine a patient's minimal erythema dose to light exposure and help to define the inciting spectrum of a photodermatosis (UVA versus UVB versus visible light). Phototesting involves irradiating the skin with varying doses of UVA, UVB, and visible light through an opaque screen with multiple openings.5 Usually the test is performed on the back. The presence or absence of solar urticaria is recorded within the first hour and the minimal erythema dose is determined after 24 hours.
• Provocative phototesting involves irradiating normal-appearing previously affected skin with the suspected causative light, either by higher doses of UV light or by natural sunlight exposure.5 Provocative phototesting is primarily used for suspected PMLE.
• Photopatch testing is useful when a topical photoallergen is suspected. It is performed by placing two identical sets of potential photoallergens on the patient's back and covering them. After 24 hours, one set is removed and that site is irradiated with UVA. The site is covered again. Twenty-four hours later, both the irradiated and control test sites are assessed for reactions. A reaction to a specific photoallergen in the irradiated site, but not the control site, indicates a photoallergy. A similar reaction in both sites suggests a contact dermatitis.5

Biopsy

• Punch biopsy of PMLE demonstrates extensive spongiosis and edema of the dermis with a deep lymphohistiocytic infiltrate. In acute phototoxic reactions, necrotic keratinocytes are observed.

• Systemic lupus erythematosus (SLE)—Sunlight can precipitate a lupus rash. Serum ANA is usually positive (see Chapter 180, Lupus: Systemic and Cutaneous).
• Porphyria cutanea tarda reactions can also be precipitated by sunlight. It tends to present with vesicles or bullae in sun-exposed areas such as the back of the hands. The bullae generally do not have any surrounding erythema, and urine for porphyrins should be positive (see Chapter 186, Other Bullous Disease).
• Dermatomyositis may cause an erythematous or violaceous eruption in sun-exposed areas. If these cutaneous findings precede the muscle weakness it can appear to be a photosensitivity reaction such as PMLE or a phototoxic drug reaction. Therefore, it is essential in the management and follow-up of patients with suspected PMLE or other photosensitivity to inquire about muscle weakness and to look for other signs of dermatomyositis on the hands and/or through laboratory tests for muscle enzyme elevations (see Chapter 181, Dermatomyositis). The dermatomyositis patient story in Chapter 181 is one in which the initial rash was thought to be a photosensitivity reaction to a new hydrochlorothiazide (HCTZ) prescription.
• Contact dermatitis appears the same as photoallergic dermatitis but is usually not limited to sun-exposed areas (see Chapter 146, Contact Dermatitis).

Nonpharmacologic

• The management of PMLE is aimed mainly at prevention. Patients who have mild disease should adopt a program of sun avoidance (see “Prevention” below). Broad spectrum (UVA and UVB blocking) sunscreen with a minimum sun protection factor (SPF) of 30 should be used whenever out of doors (Table 199-4).6 However, the SPF value of a sunscreen describes its protection factor against sunburn, which is primarily caused by UVB. The SPF does not provide sufficient information on UVA protection.7 SOR C Patients must use sunscreen liberally and frequently (reapply every 2 hours and after swimming) as an insufficiently thick application may reduce its effectiveness.8 SOR B
• Patients with severe PMLE can be desensitized in the spring with the use of phototherapy and maintained in the nonreactive state with weekly 1 hour unprotected exposure to sunlight. SOR C A course of psoralen and UVA radiation, or a course of narrow-band UVB, 3 times a week for 4 weeks provides protection.9 SOR B These treatments may induce a typical rash or erythema but otherwise have no major adverse effects.
• Avoid tobacco products since they may make PMLE worse.10 SOR B

Medications

• Acute episodes of photodermatitis respond rapidly to topical and/or oral corticosteroids. Topical steroids should provide symptomatic relief and decrease the inflammation. For more severe reactions, a course of prednisone 30 mg daily for 5 to 7 days may be used.11 SOR B
• Patients with acute drug-induced photodermatitis need to practice sun avoidance until well after the drug is discontinued. Topical and systemic corticosteroids may be used, especially with photoallergic reactions, but their efficacy is unproven. SOR C
• Nicotinamide was successful in 60% of 42 patients treated with 3 g/day orally for 2 weeks.12 SOR B

Sun protection is the primary preventative measure for patients with photosensitivity. Patients should avoid exposure to midday sun (between 10:00 am and 3:00 pm). Protective clothing such as long sleeve shirts and broad rim hats should be worn while outdoors. Fabrics that are tightly woven, thick, and/or dark-colored are useful for protection.14 Clothing treated with broad-spectrum UV absorbers is also helpful. Window film that blocks UV and some visible light can be applied to cars or homes.15

Sunscreen is important for daily use for patients with photosensitivity. Sunscreens are divided into chemical (organic) and physical (inorganic) products. Physical sunscreens block both UV and some visible light (see Table 199-4). Products containing avobenzone or ecamsule offer improved protection against UVA.

Physical blocker (inorganic) sunscreens, such as titanium dioxide and zinc oxide, work by reflecting and scattering UV and visible light. Older formulations were opaque making them cosmetically less acceptable to patients. Newer nonopaque, micronized formulations of titanium and zinc oxide have been developed but are less capable of scattering visible light and the longer wavelengths of UVA.

Chemical sunscreens may cause allergic contact dermatitis or photoallergic reactions in some patients. These patients should use titanium dioxide or zinc oxide sunscreens for protection.

• Some patients with PMLE experience less-severe reactions with successive years, but they may also worsen over time without appropriate treatment.
• The prognosis is excellent with patients when the offending agent is removed. Complete resolution of the photosensitivity may take weeks to months. Patients with persistent light reactivity beyond this have a poorer prognosis.

• Follow-up is needed if the photosensitivity persists.

• Patients with any type of photodermatitis should apply strong broad-spectrum sunscreens daily and use protective clothing (hats and shirts that cover the arms and V-neck). The sunscreen should be water resistant and applied to exposed areas before sun exposure.16 Sunscreens should be reapplied every 2 hours if there is continued sun exposure. Some of the most effective sunscreens contain stabilized avobenzone, Mexoryl, and/or titanium dioxide or zinc oxide to block UVA and UVB.
• Tell your patients that if they develop an allergy to one sunscreen, they should find another with different ingredients.
• It is important to avoid sunlight during the midday whenever possible.
• Explain to patients that phototoxic reactions may cause hyperpigmentation, which can take weeks to months to resolve. There is no guarantee that all the hyperpigmentation will go away.
• Avoid repeated rubbing and scratching, which can lead to skin thickening and chronic lichenification. Use the topical medications prescribed to treat the itching and to avoid lichenification.

Patient Resources

• DermNet NZ. Photosensitivity (Sun Allergy)—http://dermnetnz.org/reactions/photosensitivity.html.
• The Skin Cancer Foundation. Photosensitivity—A Reason To Be Even Safer in the Sun—http://www.skincancer.org/photosensitivity-a-reason-to-be-even-safer-in-the-sun.html.

Provider Resources

• American Academy of Family Physicians. Common Hyperpigmentation Disorders in Adults: Part I—http://www.aafp.org/afp/20031115/1955.html.
• eMedicine. Drug-Induced Photosensitivity—http://emedicine.medscape.com/article/1049648.
• DermNet NZ. Polymorphic Light Eruption—http://www.dermnetnz.org/reactions/pmle.html.
• Darby-Stewart AL, Edwards FD, Perry KJ. Hyperpigmentation and vesicles after beach vacation. Phytophotodermatitis. J Fam Pract. 2006;5512:1050-1053.
• Phytophotodermatitis case report and review—http://www.skinandaging.com/content/what-caused-this-rash-on-this-man%E2%80%99s-wrist-and-hand.
• eMedicine. Sunscreens and Photoprotection—http://emedicine.medscape.com/article/1119992.