Photosensitivity and photoreactions

Tanning and sunburn reactions

The visible short-term effects of UV light exposure are sunburn ( Fig. 19.1 ; see Fig. 26.16 ) and tanning. The ability to cause sunburn markedly declines with increasing wavelength. UVA light at 360 nm is 1000-fold less effective in causing skin erythema (sunburn) than UVA light at 300 nm. UVB light is largely responsible for sunburn, with peak induction 6 to 24 hours after exposure. Sunburns gradually fade during the next 3 to 5 days, as the skin starts to desquamate. Reactivity to UVB light may range in severity from a mild asymptomatic erythema to a more intense reaction, with redness accompanied by tenderness, pain, edema, and, at times, vesiculation and bulla formation, particularly the day after the sunburn first appears. If the sunburned area is extensive, constitutional symptoms may include nausea, malaise, headache, fever, chills, and even delirium. Sunburn during childhood correlates with a higher risk of developing melanocytic nevi, as well as UV light–induced skin cancers.

Tanning is also wavelength dependent and is biphasic. Immediate pigment darkening results primarily from exposure to UVA light, is caused by alteration and redistribution of melanin, and fades in 6 to 8 hours. Delayed tanning usually results from exposure to UVB and peaks at about 3 days after exposure. Fair skin is only able to tan with UVB dosages greater than the erythema threshold (i.e., a sunburn is required on type II skin; type I skin cannot tan; Table 19.1 ). In contrast, darker skin types (i.e., type III and higher) can tan significantly without burning (at suberythemogenic doses). Sunburn causes apoptosis (cell death) of keratinocytes (“sunburn cells”) or, if the dosage is high enough, induces cell cycle arrest, allowing the cell to undergo repair of their deoxyribonucleic acid (DNA) template before proliferating. Sunburn also depletes the protective Langerhans cells, causes epidermal thickening (which reduces exposure of the basal keratinocytes to UV radiation) as a protective mechanism, stimulates release of inflammatory cytokines, and induces the formation of antioxidative enzymes (which reduce oxidative DNA damage). The tan induced by UVB involves increased melanin synthesis, increased numbers of melanocytes, and increased transfer of melanosomes to keratinocytes.

The long-term effects of chronic sun exposure include photoaging, photocarcinogenesis, and immunosuppression. Given its potential to penetrate more deeply into the dermis, UVA light is thought to play a particularly important role in photoaging. UVA light, but not UVB light, is able to penetrate through window glass, even if tinted. Thus individuals who sit in offices exposed to UVA light through windows or drive cars extensively can show significant asymmetry in UVA damage on the face. An exception is the laminated glass of windshields (as opposed to the nonlaminated glass on the sides of cars), which blocks most UVA light (up to 380 nm). Window films can be applied to block UVA radiation but allow vision.

UVA light is also the light used in indoor tanning, a practice prevalent particularly among older female adolescents. ^, This practice promotes skin damage, leading to an increased risk of both melanoma and nonmelanoma skin cancer and photodamage, but no increased protection against sun exposure. ^, Indoor tanning has also led to psychological dependence and has been associated with a higher risk of other high-risk health behaviors. The danger of using tanning facilities has led to legislation to control use by minors and limitations of exposure in almost every state and reclassification by the US Food and Drug Administration (FDA) of tanning beds as class II devices that require oversight and are subject to restrictions. The prevalence of use of a tanning salon by college-aged students was 60.4% in 2009, with 33.1% using tanning salons more than five times a year. From 2009 to 2017, however, indoor tanning declined (15.6% to 5.6%) across all age groups, and among White (37.4% to 10.1%) and Hispanic (10.5% to 3.0%) female adolescents, as well as White (7.0% to 2.8%) and Hispanic (5.8% to 3.4%) male adolescents.

Many facilities now offer “safe” tanning, and these self-tanners are also available commercially. With all these self-tanners, an artificial tan is produced by dihydroxyacetone (DHA), a sugar that interacts with the stratum corneum proteins to produce a brown pigment made of polymers called melanoidins, which resist washing. Higher concentrations and more applications of DHA increase the degree of tanning. The effect of DHA is seen within 1 to 3 hours of application, peaks 8 to 24 hours after application, and persists for 5 to 7 days. Pigmentation is only lost with keratinocyte sloughing. Bronzers, which are often in tinted moisturizers or powders, sometimes contain DHA but often have other products that color skin temporarily, such as walnut shell extract, fig, or henna. Approximately 10.8% of adolescents have used a self-tanner, especially older White adolescents with a high to moderate level of sun sensitivity. Self-tanners, unfortunately, provide minimal and transient sun protection, and their use is often in conjunction with tanning salon use rather than as a substitute.

Prevention of sunburn depends primarily on the use of measures that reduce exposure to strong sunlight. This is especially important for fair-skinned individuals, particularly blue-eyed persons, redheads, blonds, and those with freckles who withstand actinic exposure poorly, burn easily, and, over the years, tend to suffer chronic effects of light exposure. The availability of sunscreens should not translate into increased sun exposure; using sensible sun protection practices beyond sunscreens should be encouraged. Prophylactic measures to reduce the impact of harmful UV rays include timing of outdoor activities to avoid peak UV light exposure between 10:00 am and 3:00 pm in the warmer seasons of the year; wearing broad-rimmed hats, sun protective clothing, and sunglasses; and staying in the shade. Light-textured materials such as T-shirts (especially when wet) give only partial protection. Clothes with a tighter weave are commercially available (e.g., www.coolibar.com ; www.solumbra.com ), or clothes can be laundered with a chemical (Tinosorb FD), which provides sun protection (e.g., SunGuard).

Sunscreens occupy an important position in the management of UV light exposure. The lifetime use of sunscreen and sun avoidance has been calculated to reduce the lifetime risk of developing UV light–induced skin cancer by 78%, although the issue of whether use of sunscreens reduces the development of nevi remains controversial. Promoting routine sunscreen use in the pediatric population is important, including among adolescents whose behaviors escape parental influence. ^, However, sun safety practices (allowing teachers time for application, avoiding outdoor activities at times of peak sun intensity, making sunscreens available to students, or asking parents to apply sunscreens before school) are not routinely used in schools. Personalized monitoring of UV radiation has been simplified by the commercial availability of devices in the forms of patches, nail art, and clip-ons that measure sun exposure through color change using photosensitive dyes and wirelessly send data to a smartphone.

Sunscreens are available in a variety of formulations, but lotions and aerosol sprays are most often used. Sunscreen labels reveal both the sun protection factor (SPF) and the capability of broad-spectrum UVA protection. The designation broad spectrum provides information about the ability of the sunscreen to protect again nonerythema effects, especially from UVA light, including immune suppression, photoaging, and skin cancer. The SPF rating can be determined by dividing the least amount of time it takes to produce erythema on sunscreen-protected skin by the time it takes to produce the same erythema without sunscreen protection. Thus individuals using a sunscreen with an SPF of 15 who normally burn after unprotected sun exposure can theoretically stay out 15 times longer before getting the same degree of erythema. Therefore the SPF rating only informs about protection against sunburn from UVB light. The additional benefit from use of a sunscreen with an SPF greater than 30 is small compared with the incremental benefit at lower SPF numbers, but higher SPF may be important for individuals with high photosensitivity or exposure to intense sunlight. However, it should be recognized that the SPF is FDA tested with a concentration of 2 mg/cm , which is more than the majority of individuals apply (equivalent to 20 g applied to the entire body of an average 9-year-old). Applying half of the FDA test concentration only achieves half or less the labeled SPF, suggesting that higher SPFs should be used unless a thick layer is applied. In a recent split-face study that assessed actual use, even SPF 100 was more effective than SPF 50 at reducing sunburn after 6 hours of exposure. The current recommendation is reapplication every few hours, as well as after swimming, periods of excessive perspiration, and washing or showering. The term waterproof is no longer allowed on labels, and sunscreens must specify the water resistance period (e.g., for 40 or 80 minutes).

The most common sunscreen components and their absorbance capacity are listed in Table 19.2 . Mineral (sometimes called inorganic ) sunscreens (titanium dioxide and zinc oxide) in the form of nanoparticles protect skin by reflecting and scattering UV and visible light (280 to 700 nm); often, both of these agents are included in a mineral sunscreen. Both titanium dioxide and zinc oxide are considered GRASE (generally recognized as safe and effective). These mineral sunscreens are recommended for use in children but may leave a highly visible white residue, especially when used in adequate amounts.

Organic sunscreens are primarily aromatic compounds that absorb light at approximately 250 to 370 nm. The two organic FDA-approved UVA-absorbing sunscreens are avobenzone and Mexoryl SX (terephthalylidene dicamphor sulfonic acid). Avobenzone is not photostable but is often in sunscreens with stabilizing ingredients. Other UVA-absorbing sunscreen ingredients are available outside of the United States, including in Europe, such as bis-ethylhexyloxyphenol methoxyphenol triazine (anisotriazine [Tinosorb S]), methylene-bis-benzotriazolyl tetramethylbutylphenol (Tinosorb M), and drometrizole trisiloxane (silatriazole [Mexoryl XL]), but the FDA has determined that insufficient evidence of safety is available to approve for US use.

Some sunscreens that were used in the past now are banned (PABA and trolamine salicylate). Oxybenzone (benzophenone-3) and octinoxate (octly methoxycinnamate) were banned in Hawaii in 2018 because of evidence of damage to coral reefs. Oxybenzone has been linked to hormone disruption, especially antiandrogenic effects, and has been found in human breast milk, amniotic fluid, urine, and plasma, attesting to its ability to penetrate skin. However, oxybenzone is a component of many nonmineral sunscreens, including in conjunction with avobenzone, and eliminating it without resorting to mineral-containing sunscreens (including in noncomedogenic products for teenagers) can be difficult, given the limited repertoire of available, FDA-approved sunscreen ingredients.

Photoallergic and allergic (i.e., not requiring sun exposure) contact dermatitis from active and inactive sunscreen ingredients should be considered in children who present with photosensitivity. In a retrospective study of 157 children, 6.4% showed positive photopatch test results. Oxybenzone and octinoxate (largely phased out) were the most common active triggers. Octocrylene is another ingredient commonly implicated. An ingredient in some sunscreens, alkyl glucoside (often listed in ingredients as arachidyl, cetearyl, cocoa, decyl, or lauryl glucoside), has experienced an increasing rate of contact allergies and was named the 2017 Allergen of the Year by the American Contact Dermatitis Society. Allergic contact dermatitis, especially to decyl and lauryl glucoside, occurs more commonly in individuals with a history of atopy. Tinosorb M (not available in the United States) contains decyl glucoside as a hidden ingredient and may be partly responsible for many cases of allergic contact dermatitis to sunscreens.

Although experts recommend that organic sunscreens be applied 30 minutes before the onset of sun exposure to enable adequate time to bind to the stratum corneum and show effectiveness, a 2018 study showed that 10 minutes before exposure may be adequate. The inorganic sunscreens (with titanium dioxide/zinc oxide) can be applied immediately before sun exposure.

Oral sunscreens containing antioxidants (e.g., lycopene, vitamins C and E) and botanicals (e.g., polyphenols such as green tea and flavonoids such as genistein) are now commercially available. They provide some protection against acute sun damage, but they are not effective in preventing sunburns or DNA damage, their long-term protective effects are not clear, and they should not replace other forms of photoprotection for children. Some of these antiinflammatory ingredients are added to topically applied sunscreens with the same issues.

The degree to which a person sunburns or tans depends on genetic factors and the natural protection of the skin. Skin types, accordingly, are ranked from skin type I, the most sensitive, to skin type VI, the least sensitive to sun damage (see Table 19.1 ). Because sun damage begins in children and is cumulative, it is strongly recommended that everyone adopt a program of sun protection and daily sunscreen use, preferably with an SPF of 15 or greater, from infancy on. Because increased melanin is not totally protective, even darker-skinned individuals can burn and should use sunscreen.

Considerable media attention has focused on the need for UV light–induced vitamin D synthesis in the skin as a rationale for sun exposure. Indeed, UVB light induces the synthesis of vitamin D ₃ in epidermal cells, and this vitamin D ₃ is then hydroxylated in the liver (to 25-OH-vitamin D ₃ ) and kidney (to 1,25-OH-vitamin D ₃ ). However, the UV light exposure that stimulates vitamin D ₃ production in the skin is inseparable from UV light exposure that is carcinogenic. Although vigorous sunscreen use may reduce the capacity of skin to produce vitamin D (and greater vitamin D deficiency has been linked to darker skin color), sunscreen use has not been linked with deficiency and oral administration of vitamin D likely suffices. The American Academy of Pediatrics recommends a minimum daily intake of vitamin D for infants, children, and adolescents to 400 IU/day, beginning shortly after birth. Patients who require strict photoprotection as treatment should be monitored for possible vitamin D deficiency and provided dietary supplementation. Evidence suggests that high doses of vitamin D ₃ (200,000 IU), given 1 hour after experimental sunburn induction, block the sunburn response.

Treatment of sunburn consists of cool compresses or cool tub baths in colloidal oatmeal (such as Aveeno), baking soda, or cornstarch; topical formulations with pramoxine or menthol; mild topical corticosteroid formulations; an emollient cream; and systemic preparations with analgesic and antiinflammatory properties, such as nonsteroidal antiinflammatory drugs (NSAIDs). When symptoms are severe, a short course of systemic corticosteroids (oral prednisone, or its equivalent, in dosages of 1 mg/kg per day, with tapering after a period of 4 to 8 days) will abort severe reactions and afford added relief.

Certain disorders predispose individuals to the adverse effects of UV light. For example, children with alopecia totalis (see Chapter 7 ), just as adults with androgenetic alopecia and balding at the vertex, have a higher risk of developing skin cancer at the exposed sites if not protected. Patients with diminished or absent melanin, as in oculocutaneous albinism (see Chapter 11 ), or with defective DNA-repair mechanisms, as in xeroderma pigmentosum, have an increased tendency to develop UV light–induced DNA damage and cutaneous malignancy. Individuals with nevoid basal cell carcinoma syndrome (see Chapter 9 ), which predisposes to the early onset of numerous basal cell carcinomas, usually have mutations in the PTCH gene, which can also be mutated by UV light exposure in sporadic basal cell carcinomas. Sunlight can also exacerbate or trigger certain dermatoses, among them acne (see Chapter 8 ); herpes simplex infection (see Chapter 15 ); lupus erythematosus, neonatal lupus, and dermatomyositis (see Chapter 22 ); Darier disease (see Chapter 5 ); pemphigus and bullous pemphigoid (see Chapter 13 ); and lichen planus and psoriasis (see Chapter 4 ).

Photodermatoses

Photosensitivity is a broad term used to describe abnormal or adverse reactions to sunlight energy in the skin. Photodermatoses must be distinguished from reactions to sunlight from exaggerated exposure, which is a normal response. Photodermatoses have been classified into four groups: (1) immunologically mediated, (2) drug or chemical induced, (3) with defective DNA repair, and (4) photoaggravation of existing conditions. ^,

Photosensitivity in a child should be suspected if the child develops a sunburn reaction, swelling, or intense pruritus after limited exposure to sunlight or shows a rash or scarring predominantly in sun-exposed areas (face, V of the neck, and dorsal surface of the arms and hands). ^, The history in a patient with a photosensitivity disorder is of great importance in determining the cause ( Table 19.3 ). Examination should focus on the distribution of lesions, including areas of sparing. In a photosensitivity disorder, the upper eyelids, postauricular and submental areas, nasolabial and neck folds, volar aspect of the wrist, and antecubital fossae tend to be spared. The morphology of the lesions may be helpful as well (urticarial versus papular versus vesicular, and the presence of lichenification, which suggests chronicity).

Phototesting can be helpful in determining the cause of an acquired photodermatosis. Exposure to UV light of different wavelengths may replicate the lesions, offering the opportunity to see morphology that may not be present at the time of the examination, confirming the suspicion of photosensitivity, and determining the UV range that triggers the disorder. Further laboratory investigations, such as antibody testing for suspected collagen vascular disease (e.g., antinuclear antibodies [ANAs], anti-ds DNA, anti-Ro, and anti-La antibodies), blood and 24-hour urine porphyrin levels, and photopatch testing in patients with suspected photoallergy, may be necessary. Performing a biopsy is rarely useful, except for suspected lupus erythematosus.

Immunologically mediated photodermatoses

Solar urticaria

Solar urticaria accounts for less than 1% of type I (immunoglobulin [Ig] E–mediated) hypersensitivity reactions and is characterized by a sensation of pruritus or burning and erythema. The arms, legs, and upper chest are most commonly affected. Areas with regular sun exposure, such as the hands and face, are less commonly involved. Onset typically is within 5 to 10 minutes of sunlight exposure and is followed almost immediately by a localized urticarial reaction confined to the exposed areas and an irregular flare reaction that may extend onto unexposed skin. Within 24 hours, lesions tend to resolve (usually in 1 to 3 hours); new lesions will not develop for 12 to 24 hours, even if subsequent exposure to sunlight occurs. Fixed solar urticaria, characterized by recurrent eruptions on the same body parts, is rare and less severe than typical solar urticaria. Delayed fixed solar urticaria, occurring 6 hours after exposure, has been described. Although the reaction is generally transient, scratching and rubbing may lead to secondary eczematization with persistent cutaneous changes. The disorder usually does not manifest until the third or fourth decade of life, and women are affected three times more often than men. It has been reported in infants and children, however, and as early as 1 week of age. ^, The condition persists for more than a decade in most affected individuals and often for a lifetime. Angioedema and systemic signs (headache, nausea, wheezing, dizziness, syncope, and, rarely, shock) have occasionally been reported in association.

The cause of solar urticaria is unclear, but the pathogenesis involves interaction of a cutaneous photoallergen with IgE-specific mast cells, leading to mast cell degranulation. Often phototesting can confirm the diagnosis and determine the wavelength range that causes the photosensitivity. If positive, whealing generally occurs within minutes. In some patients, the sensitivity involves the UVB range through the visible light range; most patients react within the range of 290 to 480 nm. A negative phototest occurs in many patients and does not exclude the diagnosis. In patients with mild forms of solar urticaria (those in whom the threshold is high), the disorder may be controlled simply by appropriate sunscreens and avoidance of prolonged unprotected sun exposure. Those individuals highly sensitive to sunlight, however, must completely avoid daytime exposure.

Nonsedating antihistamines (generally four times the recommended dose), antimalarials, corticosteroids, intravenous Ig (IVIG), and plasmapheresis have been beneficial. Omalizumab may be an option for patients with high levels of IgE who fail antihistamine therapy. ^{, ,} In some individuals, sun tolerance may be established by carefully metered, increasing exposures (“hardening”) to natural or artificial light or the oral administration of a psoralen followed by UVA (PUVA) light.

Polymorphous light eruption

Polymorphous light eruption (PMLE) is the most common of the immune-mediated disorders associated with photosensitivity, occurring in 10% to 15% of the US population. Although predominantly a disorder of women in the second and third decades of life, PMLE is well recognized to occur in children and more often in individuals with lighter skin types. Although its cause remains only partially understood, PMLE has been hypothesized to involve resistance to UV light–induced immune suppression and subsequently cell-mediated immune reactivity to a cutaneous photoantigen. An autosomal dominant inherited form of PMLE has been described in Native Americans of both North and South America. Onset of this hereditary form is in childhood, and female patients outnumber male patients 2:1.

Often referred to as sun allergy or sun poisoning, the clinical eruption consists of a group of polymorphic lesions that usually occur 1 to 2 days after intense sunlight exposure, often while on vacation. In some individuals the eruption is first seen in the spring and persists with continued sun exposure but may improve later in the summer as the skin “hardens” from UV light exposure. The lesions may range from small papular ( Fig. 19.2 ), urticarial ( Fig. 19.3 ), vesicular, or eczematous reactions to large papules, plaques, or patterns resembling erythema multiforme. A “pinpoint” variant that resembles lichen nitidus clinically and histologically occurs more often in individuals with darker skin colors. ^, The face, sides of the neck, and sun-exposed areas of the arms and hands are most often affected. In children, PMLE usually begins on the face as an acute, erythematous, eczematous eruption with small papules. Pruritus may be severe. Lesions usually involute spontaneously in 1 to 2 weeks, provided no additional exposure to sunlight occurs.

Juvenile spring eruption is considered a subset of PMLE and is characterized by photo-induced, dull-red edematous papules and papulovesicles that are largely confined to the superior helices of the ears ( Fig. 19.4 ). Lesions may become vesicular and crusted and occasionally appear on the dorsal aspects of the hands and on the trunk. Juvenile spring eruption occurs more commonly in boys than in girls and particularly between the ages of 5 and 12 years. Protuberant ears and lack of hair cover have been strongly associated, but skin color and use of sunscreen have not. Lesions heal within a week, without scarring, unless secondary infection develops. Lesions are more difficult than PMLE to reproduce by exposure to UV light, which has raised the question of whether the lesions, often appearing on a cool spring day, are more closely linked to pernio.

The diagnosis of PMLE is suggested by the character of the lesions, their distribution, and their relationship to sun exposure. Although often unnecessary, PMLE can be confirmed by provocative light testing with UVA and/or UVB (minimal erythema dose [MED] tends to be normal), which is able to reproduce the spontaneous lesions in about 50% of patients. The testing involves exposing a site that has previously reacted repeatedly for about 4 consecutive days; testing should be performed in early spring before hardening has occurred. PMLE is distinguished clinically from solar urticaria based on the time course (within hours to days after exposure rather than minutes), duration (lasts for days rather than hours), and lack of urticaria. Some patients with systemic lupus erythematosus acquire sun-induced lesions indistinguishable from those of PMLE, and serologic testing should be performed (see Chapter 22 ). In addition, erythema multiforme may be photodistributed and thus confused with PMLE ; in contrast with erythema multiforme, PMLE skin samples have shown no evidence of herpes simplex virus.

Prevention of PMLE consists of sunscreens with good coverage of the UVA spectrum (when applied adequately with 2 mg/cm ), sun-protective clothing, and the avoidance of midday sun exposure. Hardening or desensitization of skin by gradually increasing exposure two to three times weekly to narrowband UVB or PUVA light for 4 to 6 weeks before exposure helps the majority of treated patients. The addition of oral flavonoids (especially Polypodium leucotomos given for 12 weeks) or antioxidants in sunscreens has shown benefit in preventing PMLE. ^, If patients severely affected by this disorder anticipate temporary intense or prolonged sun exposure, a short course of systemic corticosteroids can be administered. Topical steroids may provide relief in mild cases. Topical vitamin D ₃ or topical liposomal DNA-repair enzymes may be of value. Antimalarials, β-carotene, and nicotinamide are of limited effectiveness.

Actinic prurigo

This photosensitivity disorder, also called hydroa aestivale and Hutchinson summer prurigo, is most commonly seen in the Indian and mestizo (mixed ancestry) populations of Mexico and other regions of Central and South America, although it has been described in the White and Asian populations. It has been seen in many children in the United States and Canada but is rare in Europe. Most cases begin in childhood before puberty. The condition is characterized by intensely itchy papules, plaques, and nodules in a symmetric distribution, along with excoriations and scars ( Figs. 19.5 and 19.6 ). Some patients can be very uncomfortable and show secondary eczematization and lichenification. Although actinic prurigo predominantly affects exposed sites on the face and distal extremities, covered areas may be involved, particularly the sacrum and buttocks. Healed facial lesions leave minute linear or pitted scars. Seasonal exacerbation at the beginning of spring with improvement in the fall is common, although the lesions commonly do not clear during the winter; greater seasonal change occurs with higher latitudes. The oral or ocular mucosae are involved in 30% to 50% of cases. Cheilitis alone is seen in 28% of patients, but 83% of patients experience pruritus, tingling, and pain of the vermilion. Ocular findings most commonly include photophobia and conjunctivitis.

The diagnosis is generally based on the clinical appearance. Biopsy of skin is generally not useful, although histologic evaluation of lip and conjunctival biopsy specimens shows the characteristic well-formed lymphoid follicles. The presence of the eruption on both exposed and covered sites, its occurrence in winter, mucosal and conjunctival involvement, persistence beyond 4 weeks, and residual scarring of skin distinguish actinic prurigo from PMLE. Photosensitivity testing for MED is abnormal in up to two-thirds of patients. Human leukocyte antigen (HLA) DRB1*0407 is found in 60% to 70% of patients with actinic prurigo but only in 4% to 8% of DR41 controls) ; HLA DRB1*0401 is present in up to 20% of affected individuals with actinic prurigo. Although individuals with PMLE do not show these associations, 35% of patients with typical actinic prurigo have a history that suggests coexistence of actinic prurigo and PMLE or transition from one to the other. Although the cause of actinic prurigo is unknown, the strong association with HLA markers suggests a role for major histocompatibility complex–restricted antigen presentation in the pathomechanism of the condition.

The disorder often has a chronic course that persists into adulthood; however, spontaneous resolution may occur during late adolescence. Vigorous sun protection and use of topical antiinflammatory agents for the pruritus lead to improvement in most patients. Short courses of systemic steroids can be helpful, but antimalarials have not had much effect. Complete resolution may require the addition of thalidomide (usually 50 to 100 mg/day), which results in rapid clearing. Oral cyclosporine and azathioprine have had some success in a few refractory cases. The gradual introduction of exposure to narrowband UVB light has also helped some patients.

Hydroa vacciniforme

Hydroa vacciniforme (HV) is a rare disorder known to result from chronic Epstein–Barr virus (EBV) infection. ^, Although it is considered a more benign photodermatosis in white children, a more persistent and severe form has been described primarily in children from Latin America and Asia. The classic lesions tend to appear each summer in children on uncovered parts of the body after exposure to sunlight. Boys are more often affected than girls. Rare familial cases have been described. The mean age of onset is 5 years in Whites and 8 years in others. The disease usually flares after sun exposure, and most patients show sensitivity to UVA light in monochromator phototesting, which may induce papulovesicular lesions. Biopsy of an active lesion showing reticular degeneration with EBV RNA in lymphocytes confirms the diagnosis. Detection of high levels of circulating EBV DNA (better in whole blood than in serum or plasma) also helps with the diagnosis.

The primary lesion is a pruritic edematous papule, vesicle, or bulla that occurs within hours or days on uncovered surfaces exposed to sunlight. Itching and burning, as well as mild constitutional symptoms, may occur a few hours before the outbreak of the cutaneous lesions. Lesions tend to appear on the face, the sides of the neck, and extensor surfaces of the extremities, and are arranged symmetrically over the nose, cheeks, ears, and dorsal surfaces of the hands ( Fig. 19.7 ). The vesicles or bullae usually develop on an erythematous base and initially are rather tense. These are followed by central necrosis and umbilication that leads to healing with individual or confluent varioliform scarring within 1 to 2 weeks ( Fig. 19.8 ). Mild conjunctivitis or keratitis, as well as corneal epithelial denudement, may be associated. In most, HV involutes spontaneously by the late teenage years with a mean duration of 9 years, but persistence into adulthood has been described.

The disorder can also be a more severe, persistent vesiculonecrotic eruption with frequent oral lesions and even cartilage or bone destruction, particularly in pediatric patients from Central and South America and Asia. Patients have marked facial edema, hemorrhagic bullae, atrophic scarring, and severe disfigurement in both sun-exposed and sun-protected sites. Patients often show an exaggerated hypersensitivity response to mosquito bites, in addition to the response to sunlight. ^, In some, systemic disease develops, with fever, hepatosplenomegaly, abnormal liver function testing, lymphadenopathy, leukopenia, and hemophagocytosis (now called HV-like T-cell lymphoproliferative disease). This HV-like lymphoproliferative disorder is associated with higher-titer latent Epstein–Barr virus infection and monoclonal T-cell receptor gene rearrangements (see Chapter 10 ). However, there is no clinical or pathologic feature that predicts the progression.

Treatment of HV consists of strict sun protection, including broad-spectrum sunscreens (SPF at least 30), protective clothing, and avoidance of midday sun exposure. No intervention has been uniformly successful. Antivirals (acyclovir, valacyclovir), antimalarial drugs, thalidomide, β-carotene, oral fish oils, and “hardening” by treatment in the spring with low-dose narrowband UVB light have been used with some therapeutic success. Only stem cell transplantation is curative for those with more severe disease. The psychosocial and emotional impairment of HV on quality of life is significant, given the extensive disfigurement from scarring and the effect on daily life of strict sun avoidance. Because of the potential risk of HV progression to HV-like lymphoproliferative disease, patients should be closely monitored for at least 10 years after diagnosis.

Photosensitivity induced by exogenous sources

Photosensitivity reactions may be phototoxic (photoirritant) or photoallergic ( Table 19.4 ). Exogenous photosensitizers may reach the skin by topical or systemic routes. The clinical course is brief, and elimination of the offending drug or sunlight exposure usually results in improvement. In rare cases, however, the photosensitivity may persist for months after the last known exposure to the offending chemical. Such individuals are known as persistent light reactors, and the eruption (chronic actinic dermatitis) ranges from a chronic dermatitis initially restricted to sun-exposed surfaces to thickened hyperpigmented plaques. This rare disorder generally affects men and not pediatric patients.

Phototoxicity

Phototoxic reactions are common and can be likened to a primary irritant reaction. Phototoxic reaction refers to a nonimmunologic exaggerated sunburn or sunburn-like reaction characterized by erythema (and at times swelling and blistering), occurring within a few minutes to several hours (usually within a period of 2 to 6 hours) after exposure to UVA light and followed by hyperpigmentation and desquamation confined to the exposed areas. This type of sensitivity usually occurs with the first exposure to the photosensitizing substance, when the systemic or percutaneous absorption of the sensitizing substances is in high enough concentration to result in a photo-induced cutaneous reaction.

Plant-induced photosensitivity (phytophotodermatitis) is the most common phototoxic reaction of children. The large majority are phototoxic reactions caused by the presence of furocoumarin compounds (psoralens) found widely in such plants as Rutaceae (e.g., limes and lemons), Umbelliferae (e.g., parsnips, carrots, dill, parsley, meadow grass, common rue, giant hogweed, and celery, most often celery infected with a fungus that causes pink rot disease), and Moraceae (e.g., fig). Psoralens can also reach the skin after ingestion, as has been noted after ingestion of contaminated celery and subsequent outdoor and tanning salon UV light exposure. With systemic ingestion, all sun-exposed areas are susceptible to reaction. Psoralens have also been used therapeutically in topical or oral formulations in combination with UVA light (PUVA therapy) as treatment of psoriasis and vitiligo; given the safety issues with PUVA, this intervention is rarely used in children. Furocoumarins can also be components in Chinese herbal medications. Inhalation of traces of giant hogweed have been reported to cause obstructive pulmonary symptoms, and contact with the eye can lead to blindness.

Phytophotodermatitis usually begins within a day after exposure to the furocoumarin and sunlight, ranges in severity from mild erythema with or without erosion to severe blistering ( Fig. 19.9 ), and eventuates in a characteristic dense inflammatory hyperpigmentation. A bizarre linear streaking configuration of the dermatitis ( Fig. 19.10 ), with subsequent hyperpigmentation, especially on the face, chest, hands, and lower legs of children, is characteristic. At times, only the hyperpigmented streak appears without prior erythema ( Fig. 19.11 ). The purple coloration of skin and bizarre patterning can be mistaken for child abuse and the blistering for herpes simplex infection. Extensive hand involvement can be noted from squeezing lime juice ( Fig. 19.12 ). Streaks on the trunk have been noted after dripping of lime juice (sometimes used as a hair rinse or in drinks), and thumbprint-shaped macules on the lateral aspects of the trunk may be described after a parent with furocoumarins on the fingers picks up a child. Usually no treatment is necessary once the diagnosis is made, and the often-intense hyperpigmentation fades spontaneously over several weeks to months. However, severe burns have been induced in children by contact with phototoxins, especially giant hogweed and prolonged sunlight exposure, and have required debridement and surgical wound closure. ^{, ,}

Phototoxicity may present with a variety of manifestations. For example, exaggerated sunburn reactions can occur with thiazide diuretics, tetracyclines ( Fig. 19.13 ), retinoids, vemurafenib, voriconazole, ciprofloxacin, and others, whereas skin fragility and blisters (pseudoporphyria) are the typical manifestation of exposure to NSAIDs, and telangiectasia results from calcium channel antagonists. Photoonycholysis most commonly occurs after administration of doxycycline (see Chapter 8 , Fig. 8.17 ). The phototoxicity from voriconazole, used to prevent fungal infections in transplant patients, occurs in 20% of treated children overall and in 47% of children treated for more at least 6 months ^, ; a dosage of at least 6 mg/kg twice daily has also been associated with a higher risk of developing voriconazole-induced phototoxicity. The eruption can be can be confused with graft-versus-host disease in these immunocompromised patients and has been associated with a 4.6% risk of developing nonmelanoma skin cancer in areas that had a phototoxic reaction at a mean age of 15.5 years.

Pseudoporphyria is a nonimmunologically mediated phototoxicity reaction characterized clinically by increased cutaneous fragility, vesiculobullae, and histopathologic features similar to those of patients with porphyria, but levels of porphyrins are normal. It has been described in approximately 11% of children taking NSAIDs, especially naproxen sodium ( Fig. 19.14 , for juvenile idiopathic arthritis), and is especially common in patients with blue/gray eye color and fair skin. The disorder has also been described in individuals receiving other NSAIDs, dapsone, ciprofloxacin, furosemide, imatinib, ^, metformin, nalidixic acid, tetracyclines, retinoids, amiodarone, pyridoxine/vitamin B6, and voriconazole. ^, A similar, if not identical, disorder has also been described in patients receiving hemodialysis ( Fig. 19.15 ).

A careful history and the presence of normal porphyrin levels in serum, erythrocytes, urine, and feces will generally establish the diagnosis. The cutaneous fragility tends to reverse rapidly on withdrawal of the causative medication but may only gradually reverse or even persist with new lesions for up to 1 month after discontinuation of the medication. Pseudoporphyria associated with hemodialysis has responded to treatment with N-acetylcysteine or glutathione. Disfiguring facial scarring is a sequela in some affected children.

Photoallergy

Photoallergy is relatively uncommon and presumably is a form of cell-mediated delayed hypersensitivity. ^, The individual must first be sensitized to the allergen, which can require 7 to 10 days. When exposed to UV light, the light is absorbed by the photoantigen, which is thought to cause a change in the molecule. Instead of sunburn-type reactions, photoallergic responses are generally characterized by immediate urticarial or delayed papular or eczematous lesions that are not followed by hyperpigmentation. After the first sensitization, subsequent photoallergic reactions generally appear within 24 hours, even after very brief periods of exposure. Sunscreens with chemical components (especially benzophenones) are the leading cause because of their extensive use ( Fig. 19.16 ), although the risk of reaction with sunscreens containing these agents is less than 1% of that for allergic contact dermatitis. ^, In the past, children showed photoallergic reactions to salicylanilides (antimicrobial agents formerly in soaps but now only in industrial cleaners) and fragrances (musk ambrette, oil of bergamot). These chemicals are no longer used in personal products, but children or adolescents have been known to find a cologne with oil of bergamot, apply it to the skin, and develop berloque (berlock) dermatitis after UV exposure. Promethazine hydrochloride cream and topical nonsteroidal antiinflammatory agents have caused photoreactions.

Suspected photoallergic contact dermatitis may be confirmed by photopatch testing. Photopatch testing is similar to traditional testing for contact dermatitis (see Chapter 3 ), except that two sets of patch tests are placed on the back. Twenty-four hours later, one set is uncovered and irradiated with UVA light. The following day a comparison is made of the covered and irradiated sites. A positive test reproduces the clinical eczematous lesion at the phototest site. Therapy is treatment with topical antiinflammatory agents and avoidance of exposure to the offending antigen.

Genetic disorders associated with photosensitivity

Photosensitivity is a prominent feature of several genetic disorders, many of which are associated with defective DNA repair. Some of these are described elsewhere in this text, such as Kindler syndrome (see Chapter 13 ), trichothiodystrophy (see Chapter 7 ), and ataxia-telangiectasia (see Chapter 12 ).