Version May 2024
INTRODUCTION — Photosensitivity disorders of the skin are conditions in which an abnormal cutaneous response occurs after exposure to ultraviolet (UV) radiation or visible light. The major categories of photosensitivity disorders are idiopathic photodermatoses, photodermatoses due to exogenous or endogenous agents, photoexacerbated dermatoses, and photosensitive genodermatoses and will be reviewed in this topic review (table 1). Photosensitivity disorders occur in both individuals with lightly pigmented and heavily pigmented skin. In a United States study of 1080 patients with photodermatoses, polymorphous light eruption (PMLE) was more common in Black people, and photoallergy and phototoxicity, phytophotodermatitis, porphyria, and solar urticaria were diagnosed more commonly in White people [1].
An overview of photosensitivity, including photobiology, patient evaluation, and photoprotection, is discussed separately. PMLE, which is a type of idiopathic photodermatosis, is also discussed separately. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection" and "Polymorphous light eruption".)
THE IDIOPATHIC PHOTODERMATOSES — The idiopathic photodermatoses are a group of photosensitivity disorders whose pathogenesis remains unclear. Many of these disorders have features suggesting that they are immunologically mediated.
The idiopathic photodermatoses include polymorphous light eruption (PMLE), actinic prurigo, hydroa vacciniforme, chronic actinic dermatitis (CAD), and solar urticaria (table 1).
Polymorphous light eruption — Polymorphous light eruption (PMLE) is the most common idiopathic photodermatosis and is sometimes colloquially called "sun poisoning" or "sun allergy." PMLE and juvenile spring eruption, a PMLE variant, are reviewed separately. (See "Polymorphous light eruption".)
Actinic prurigo — Actinic prurigo, also known as Hutchinson's summer prurigo, familial or hereditary PMLE of Native Americans, or hydroa aestivale, is a photo-induced pruritic eruption often considered a variant of PMLE. Actinic prurigo and PMLE may share a common pathophysiologic basis, although actinic prurigo has distinct clinical features [2].
Epidemiology — Onset of actinic prurigo usually occurs in childhood, although it can also first present in adults [2-7]. Patients with childhood onset may spontaneously improve in adolescence, but the condition can persist into adulthood [3,4]. Actinic prurigo is more common in females [2,3], although studies from Singapore, Thailand, and Taiwan note a greater number of male patients in the adult-onset cohort [5-7].
Actinic prurigo is most commonly seen in Mestizos (ie, individuals of mixed American Indian and European ancestry), although other ethnicities may be affected as well [8]. A family history of actinic prurigo is present in up to 50 percent of patients [9].
Pathogenesis — Lesions of actinic prurigo are induced by exposure to ultraviolet (UV) radiation. Both ultraviolet A (UVA) and ultraviolet B (UVB) have been implicated; UVA wavelengths elicit the disease in most patients [10]. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Phototesting'.)
Genetic susceptibility is important. Actinic prurigo is associated with an HLA-DR4 polymorphism [2,11]. The specific locus, HLA-DRB1*0407, has been identified in 60 to 70 percent of patients [2,3]. In affected subjects from Singapore, there is a closer association with HLA-DRB1*0301 [12].
Clinical manifestations — The onset of actinic prurigo usually occurs in the spring, when more time is spent outdoors and more skin is exposed. The lesions can persist through the summer and, unlike PMLE, may even extend into the winter months.
Pruritus is characteristic and significant. Commonly, lesions are symmetrically distributed on sun-exposed skin (eg, forehead, cheeks, chin, ears, forearms), but covered sites such as the back and buttocks may also be affected [10]. Typical lesions are papulonodular and often have a hemorrhagic crust (picture 1A-B). Eczematous changes and lichenification are also seen. Occasionally, mild scarring may be present.
Actinic cheilitis is a distinguishing feature of the disease and can be seen with other cutaneous findings or as the sole clinical manifestation. Ocular involvement, which manifests as conjunctivitis or pseudopterygium, can occur, although it is rare in White patients [13,14].
Patients who have been evaluated with the Dermatology Life Quality Index (DLQI) report a major impact on their quality of life [15].
Diagnosis — The diagnosis of actinic prurigo is often based upon clinical findings. The differential diagnosis includes prurigo nodularis, arthropod bites, and excoriated eczema.
Biopsy findings are not diagnostic but may help to exclude other diseases. Histopathologic features in early lesions include epidermal spongiosis and a superficial and deep perivascular mononuclear infiltrate. More advanced lesions may also exhibit lichenification, focal papillary dermal fibrosis, and irregular epithelial hyperplasia [16]. Biopsies of cheilitis in actinic prurigo reveal characteristic dense lymphocytic infiltrates with distinctive, well-formed lymphoid follicles [16].
Phototesting can be helpful. A case series of 21 patients with actinic prurigo reported reduced minimal erythema doses (MEDs) in 60 percent [3]. Photoprovocation testing is positive in 60 to 70 percent of patients [13]. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Phototesting'.)
Serum immunoglobulin E (IgE) levels have been reported to be elevated in nearly one-half of patients and are associated with moderate or severe disease [17].
Treatment — The implementation of sun-protective practices is important for the management of actinic prurigo. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Photoprotection'.)
Topical corticosteroids can offer additional relief for some patients; in a case series of eight patients with actinic prurigo, intermittent 3- to 14-day courses of topical clobetasol led to marked improvement in seven patients [18]. Topical application of the topical calcineurin inhibitor tacrolimus has also been reported to be effective in patients with milder disease [8]. Oral glucocorticoids can temporarily improve symptoms during acute exacerbations [3].
Phototherapy with narrowband ultraviolet B (NBUVB) [19] or psoralen plus ultraviolet A (PUVA) [20] is a therapeutic option in patients with persistent symptoms. In most situations, a short course of oral corticosteroids is administered at the beginning of phototherapy to prevent a flare of disease. Treatment is initiated in the spring, prior to seasonal recurrence, since the disorder typically worsens during the summer months. In a case series of five patients treated with PUVA twice weekly for 15 weeks, all patients reported increased tolerance to sun exposure after four weeks [20]. By the end of therapy, measurements of MEDs approximated those of normal skin, and the subjects were able to tolerate summer sun exposure without the recurrence of symptoms.
In a separate case series, six patients with actinic prurigo treated prophylactically with 10 NBUVB treatment sessions delivered over two to five weeks exhibited improved tolerance to sun exposure after completing therapy [19]. During the treatment cycle, pruritus developed in five patients. Pruritus was associated with induction of actinic prurigo in four patients.
Phototherapy is not curative, and symptoms of actinic prurigo eventually recur after treatment is discontinued [3].
Thalidomide has been successful in patients with resistant disease in case series and case reports [3,21-25]. In one case series, 32 out of 34 patients with actinic prurigo improved with thalidomide [21]. The potential for side effects such as peripheral neuropathy and teratogenicity must be carefully considered prior to initiating thalidomide therapy. There are reports of successful management with dupilumab [26,27] and with Polypodium leucotomos supplements [28].
Thalidomide is prescribed at a dose of 50 to 100 mg/day and is subsequently tapered to the lowest dose that sustains improvement [29]. Maintenance doses as low as 50 mg/week have been used, and cases in which patients have been able to discontinue treatment without recurrence have been reported [10]. In one small case series, pentoxifylline 1200 mg per day for six months was an effective treatment [30]. Cyclosporine 2.5 mg/kg per day and azathioprine (50 to 100 mg per day) are other options in resistant cases [6,31].
Hydroa vacciniforme — Hydroa vacciniforme is a rare photodermatosis of childhood, characterized by vesicular lesions on sun-exposed skin that eventually heal, leaving depressed scars.
The prevalence of hydroa vacciniforme has been estimated to be 0.34 per 100,000 [32]. The disease onset typically occurs in childhood, with a mean duration of nine years from symptom onset to resolution [32]. Resolution usually occurs by adolescence or young adulthood, although symptoms may persist throughout life in some patients. Males have been noted to have a more severe disease, with later onset and longer course than in females [32]. The disease is more common in Latin America and Asia than in the United States and Europe [33].
Pathogenesis — The pathogenesis of hydroa vacciniforme is unclear. Photoprovocation testing with UVA produces skin findings that resemble lesions induced by natural sunlight in some patients [32,34].
The presence of latent Epstein-Barr virus (EBV) in typical hydroa vacciniforme has been reported and may be a contributing factor in the etiology [35,36]. Biopsy specimens taken from lesions provoked by repeated exposure to UVA radiation have significantly more EBV-positive cells than adjacent normal skin, and, on electron microscopy, viral particles can be found in keratinocytes from lesional skin but not in normal skin. Moreover, greater amounts of EBV DNA have been found in blood samples from individuals with hydroa vacciniforme compared with individuals with other photosensitivity disorders [34].
Clinical findings — Hydroa vacciniforme occurs primarily in the summer. Sunlight induces the lesions on exposed areas of skin, most commonly the face and dorsal hands, within hours of sun exposure. The eruption is symmetric, exhibiting erythematous macules that progress to tender papules, vesicles, and crusts (picture 2A-B). Lesions are associated with pruritus or a burning sensation. Unlike PMLE, hydroa vacciniforme heals with scarring. In rare cases, patients may also experience malaise, fever, or headaches during flares.
Rarely, ocular findings may be present, such as photophobia, lacrimation, conjunctivitis, corneal infiltration with vascularization, keratitis, or uveitis [37-39]. Referral to an ophthalmologist is recommended if eye symptoms are present.
Diagnosis — The diagnosis of hydroa vacciniforme is clinical, based upon the morphology of the lesions (picture 2A-B). Photoprovocation tests may be performed to establish the diagnosis in equivocal cases. Skin biopsy may be helpful but requires correlation with clinical findings. Histopathologic examination of active lesions reveals intracellular and intercellular edema, reticular degeneration, vesiculation, and epidermal necrosis. Dermal findings include a perivascular lymphohistiocytic and neutrophilic infiltrate [16]. Photoprovocation tests may be performed to establish the diagnosis. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Phototesting'.)
The differential diagnosis includes erythropoietic protoporphyria (EPP), bullous lupus erythematosus, and recurrent facial herpes simplex [40]. Porphyrin studies are helpful in excluding EPP (see "Erythropoietic protoporphyria and X-linked protoporphyria"). Hydroa vacciniforme and bullous lupus erythematosus can be distinguished histologically. In addition, antinuclear antibodies and biopsy specimens for direct immunofluorescence are usually positive in lupus but negative in hydroa vacciniforme.
The role of serology for EBV in differentiating hydroa vacciniforme from other photosensitivity disorders has not been systematically evaluated.
Treatment — Hydroa vacciniforme is difficult to treat. All patients should be encouraged to engage in strict photoprotection via avoidance of sun exposure and the use of broad-spectrum sunscreens and sun-protective clothing. Individuals with severe disease may need to apply films that block wavelengths within the UV spectrum to automobile and house windows. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Photoprotection'.)
In a case series of five patients, three were found to respond to photodesensitization with NBUVB [32]. Other treatments include antimalarials, intermittent corticosteroids, azathioprine, cyclosporine, and dietary fish oil [41-44]. There is a single case report of a patient who responded to acyclovir and valacyclovir [45]. There is a report of two adult cases with EBV-associated hydroa vacciniforme-like lymphoproliferative disease treated with minocycline and topical pimecrolimus cream 1%, respectively [46].
Atypical hydroa vacciniforme-like eruption — There are multiple reports of atypical hydroa vacciniforme-like eruption associated with chronic or latent EBV infection and lymphoproliferative disorders in children and adults [33-40,47,48]. These patients have associated symptoms of lymphadenopathy, hepatosplenomegaly, fever, and fatigue that are not seen with typical hydroa vacciniforme. Skin lesions are more severe and may be provoked by sun exposure as well as mosquito bites [33,49,50]. Atypical hydroa vacciniforme-like lymphoproliferative disease is much more common in non-White patients than in White patients [33]. The relationship between atypical hydroa vacciniforme-like lymphoproliferative disease and typical hydroa vacciniforme is uncertain. Evaluation for a lymphoproliferative disorder should be based on clinical presentation and suspicion.
Chronic actinic dermatitis — CAD is a rare, persistent, photo-induced eczema affecting the exposed skin. Older males with a history of significant occupational or recreational sun exposure are most commonly affected, although it is becoming more frequent in younger patients and in females [51,52]. Both light- and dark-skinned individuals can develop CAD [52-54]. Interestingly, in individuals with higher Fitzpatrick skin types (V and VI), CAD has been noted to have earlier onset and to occur more frequently in females [55].
Many patients have a coexisting allergic contact dermatitis, frequently to airborne allergens, but also to carba mix and paraphenylenediamine. Photocontact allergies are also frequent. In the past, these were primarily plant photoallergens. The most common photoallergens associated with CAD are agents found in sunscreens, especially avobenzone and oxybenzone. Among the plant photoallergens, Tanacetum vulgare (common tansy) and Taraxacum officinale (common dandelion) predominate [51,52,56,57]. An association with atopic dermatitis [54,58-60] and with HIV infection has also been reported [61,62].
Pathogenesis — The pathogenesis of CAD is not completely understood, although it is thought to have an immunologic basis. Consistent with this hypothesis is the observation that the dermal infiltrate in lesional skin is predominantly composed of CD8+ cytotoxic suppressor T cells, similar to that seen in allergic contact dermatitis [63], and that the disease is frequently treated with immunosuppressive agents. One theory is that CAD is a delayed-type hypersensitivity reaction against a photo-induced endogenous antigen. An alternative hypothesis is that CAD represents the response to an exogenous photosensitizer, which persists for a prolonged period of time in the skin [64,65]. CAD begins in most cases with an abnormal sensitivity to UVB, UVB and UVA, or, uncommonly, to UVA alone. With time, signs and symptoms can be elicited by a wider spectrum of wavelengths, sometimes extending into the visible spectrum. Prolonged exposure to compact fluorescent lamps, which emit small amounts of UVA and UVB, is thought to be a provocative factor in some CAD patients [66].
Genome-wide analysis of mRNA and long noncoding RNA profiles have been conducted in four patients with chronic actinic dermatitis. Compared with normal controls, differential expression of both annotated and novel long noncoding RNAs were observed, especially in the inflammatory and immune response-related pathways [67]. This included long noncoding RNAs that regulate TNFAIP, a key molecule in the tumor necrosis factor (TNF) pathway.
Clinical manifestations — CAD presents with eczematous patches distributed on the face, neck, dorsal hands, scalp, and upper chest, often with sharp demarcations at lines of clothing. Lichenification and erythematous, infiltrated papules and plaques may also be seen (picture 3A-B). Although initially present exclusively on sun-exposed skin, the disease can progress over the years to unexposed areas as well. In severe cases, generalized erythroderma may develop [68]. Palmar and plantar eczema are not uncommon. Patients may have abnormal cutaneous findings year round, but the eruption typically worsens in the summertime.
Three different clinical pictures, formerly considered distinct entities, are recognized: actinic reticuloid, photosensitive eczema, and persistent light reactivity. Transition from one form to another can occur [69]. Symptoms of CAD often persist for years; approximately 25 percent of patients go into remission within 10 years [51,70].
Diagnosis — The diagnosis of CAD is based upon the clinical finding of a persistent eczematous eruption affecting primarily the sun-exposed skin in older individuals and the documentation of increased sensitivity (decreased MED) to UVB, often to UVB and UVA, and occasionally to visible light by phototesting [51,52,58].
Patch testing and photopatch testing are also useful for diagnosis. Patch tests and photopatch tests are used to identify coexisting contact allergens and/or photoallergens that may exacerbate the disorder [54,71]. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Diagnostic studies'.)
Skin biopsy may be helpful for diagnosis. Histopathologic findings include epidermal spongiosis, lymphocyte exocytosis, and a superficial and deep perivascular, lymphohistiocytic infiltrate. Lymphocyte exocytosis and small collections of atypical mononuclear cells in the epidermis, resembling the Pautrier microabscesses of mycosis fungoides, may also be seen [16].
Phototesting is helpful to distinguish CAD from cutaneous lymphoma since photosensitivity is not a usual feature of cutaneous T cell lymphoma (CTCL), although occasionally CTCL can exhibit increased photosensitivity [29,72]. Circulating Sézary cells can be found either in CAD or in CTCL [68]. Serologic testing for lupus (ANA, anti-Ro, anti-La) and for HIV is indicated in younger individuals.
Overlapping clinical and histologic findings make it difficult to differentiate CAD from photoaggravated atopic or seborrheic dermatitis, contact dermatitis, PMLE, acute and subacute cutaneous lupus erythematosus (SCLE), systemic drug-induced photosensitivity, and CTCL, although age of onset and certain historical features (eg, drug exposure) may be helpful in some cases. Rarely, the two disorders may coexist.
Treatment — Treatment of CAD is often difficult. Strict sun protection should be emphasized but often is ineffective as a sole measure. (See "Selection of sunscreen and sun-protective measures".)
Avoidance of known contact and photocontact allergens as well as photosensitizing drugs is recommended [58]. Broad-spectrum sunscreens should be used only after patch and photopatch tests rule out a sunscreen allergy [73]. Although no randomized trials have evaluated these therapies, topical corticosteroids, topical tacrolimus and pimecrolimus [74-78], and/or emollients may help.
For more severe cases, systemic therapy may be prescribed. Azathioprine was effective in one small, randomized trial [79]; cyclosporine [80], mycophenolate mofetil [81], and tofacitinib [82] have led to improvement in anecdotal reports. Low-dose PUVA or NBUVB, initially given with oral glucocorticoids to decrease treatment-induced flares, have been effective in small case series [83-85]. In one report, topical tacrolimus 0.1% applied at night under occlusion was successfully used in five patients with CAD resistant to systemic immunosuppressive agents [86]. Several small case series and case reports have found that dupilumab provides clinical benefit in some patients [87-90]. There are two reports of patients with recalcitrant chronic actinic dermatitis who experienced a marked improvement with oral tofacitinib [82,91].
Solar urticaria — Solar urticaria is a rare variant of urticaria. Pruritic, erythematous wheals appear within 5 to 10 minutes of sun exposure and resolve within 24 hours (picture 4). Symptoms can be induced via exposure to UVA, UVB, or visible light. The precise wavelengths vary from individual to individual.
Solar urticaria has been postulated to develop due to the modification of endogenous proteins by UV radiation and/or visible light, which then causes cross-linking of IgE molecules attached to mast cells, leading to the release of histamine and other mast cell mediators. Nonimmunologic mechanisms, such as UVA-induced mast cell damage, have also been proposed. The genetic and environmental influences remain to be determined [92].
Phototesting is useful to confirm the diagnosis and typically results in the appearance of urticaria within minutes. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Phototesting'.)
Pharmacologic therapy or photodesensitization with low-dose PUVA or NBUVB initially given with oral glucocorticoids is usually required for management [85]. Omalizumab, a neutralizing antibody to IgE, has been reported to be effective [93,94].
A detailed review of the clinical manifestations, diagnosis, and treatment of solar urticaria is provided separately. (See "Physical (inducible) forms of urticaria", section on 'Solar urticaria'.)
PHOTOSENSITIVITY DUE TO EXOGENOUS AGENTS — Photosensitivity induced by exogenous agents refers to a process in which chemicals or drugs that are ingested or applied to the skin promote a photosensitivity reaction when the individual is exposed to sunlight. In one study, photosensitivity was responsible for approximately 20 percent of adverse drug reactions in older adults [95]. This type of photosensitivity is usually divided into phototoxic and photoallergic reactions; phytophotodermatitis is a special form of toxicity elicited by photosensitizing chemicals in plants. Phototoxic and photoallergic reactions differ in their clinical features and causative agents (table 2) [96].
Phototoxicity — Phototoxicity results from direct tissue or cellular damage following ultraviolet (UV) irradiation of a phototoxic agent that has been ingested or applied to the skin. Phototoxicity can occur in any individual in whom the threshold concentration of the chemical or drug has been reached [96-99]. By contrast, photoallergy is a cell-mediated immune response elicited by small amounts of compound in previously sensitized individuals (table 2).
Drug-induced — The majority of drug-induced photosensitivity reactions are phototoxic. Common offenders are listed in the table (table 3) [96,100].
Phototoxic reactions appear as an exaggerated sunburn (picture 5A-C). The reaction usually evolves within minutes to hours of sun exposure and is restricted to exposed skin [97]. In severe cases, vesicles or bullae may be seen [64]. Skin biopsy findings are identical to those of ordinary sunburn, with vacuolated and apoptotic keratinocytes [16].
Most phototoxic drugs are activated by ultraviolet A (UVA) rather than ultraviolet B (UVB) radiation. Aminolevulinic acid, methyl aminolevulinate, and porfimer sodium are activated by wavelengths in the visible spectrum. A special form of phototoxicity occurs following contact with tar compounds. Tar phototoxicity occurs primarily in road workers and roofers who employ tar in their occupations. Occasionally, it can be seen in individuals who use tar-containing shampoos. A burning and stinging pain, called "tar smarts," occurs within minutes of exposure to sunlight.
Phytophotodermatitis — Topical exposure to plant-derived substances may also cause a phototoxic reaction termed phytophotodermatitis.
The most common plants that cause phytophotodermatitis are in the Apiaceae (ie, Umbelliferae) and Rutaceae families [101]. Commonly encountered members include celery, wild parsnip, and parsley (Apiaceae), as well as lemons and limes (Rutaceae). The sap of fig trees (Ficus carica) and seeds of Psoralea corylifolia are additional inducers of phytophotodermatitis [102].
A list of plants that may cause phytophotodermatitis is provided (table 4). All of these plants contain furocoumarins, of which psoralens and angelicins are the most notable examples. The furocoumarins alone are inactive, but, following exposure to UVA radiation, they may induce a photosensitivity reaction.
Phytophotodermatitis occurs most commonly after exposure to limes, especially in bartenders and others who squeeze limes when making cocktails and other drinks (picture 6A). Other citrus fruits contain furocoumarins and may infrequently cause a phytophotodermatitis. Phytophotodermatitis is also seen in gardeners, children who come in contact with plants and weeds while playing in fields and meadows, chefs, and food-industry workers, especially those who handle celery.
Patients with phytophotodermatitis typically present with erythema, edema, and bullae in linear or bizarre configurations on sun-exposed skin that reflect the manner in which they have come in contact with the plant (picture 6A-C). For example, people who develop phytophotodermatitis from exposure to plants in meadows and fields often have a linear distribution to their cutaneous eruption (picture 7). The clinical findings appear approximately 24 hours after sun exposure. Lesions are not pruritic and may be painful. As the acute eruption clears, it is replaced by hyperpigmentation that may take months to years to resolve. It should be noted that often the preceding erythema is inapparent and only the hyperpigmentation is observed.
Generalized phototoxic reactions secondary to the ingestion of large quantities of furocoumarins are rare. A few cases of generalized phototoxic reactions have occurred following psoralen plus ultraviolet A (PUVA) therapy or tanning salon use in patients who had consumed large amounts of celery [103-105]. Hypericin, a non-furocoumarin photosensitizing substance found in St. John's wort (Hypericum perforatum), can also lead to a generalized phototoxic reaction on sun-exposed skin after ingestion of high doses of the plant extract. (See "Clinical use of St. John's wort", section on 'Adverse effects'.)
Other manifestations — Other manifestations of phototoxicity include pseudoporphyria, usually caused by nonsteroidal anti-inflammatory drugs (NSAIDs; most commonly naproxen), tetracycline, voriconazole, or furosemide [97,106]; photo-onycholysis due to tetracyclines, psoralens, and NSAIDs; and slate-gray hyperpigmentation due to amiodarone, chlorpromazine, tricyclic antidepressants, or diltiazem [72,96,97]. Pseudoporphyria presents with the features of skin fragility and subepidermal blisters typically seen in porphyria cutanea tarda.
Photoallergy — Photoallergy is a delayed-type hypersensitivity reaction to an allergen whose antigenicity has changed after exposure to UV radiation (photoallergen). Once the photoallergen has formed, the subsequent steps in the pathogenesis of the reaction are identical to allergic contact dermatitis [72,96-99]. As in other allergic contact dermatitis reactions, affected individuals must have been previously sensitized to the photoallergen. Similar to phototoxic reactions, most photoallergic reactions are initiated by UVA rather than UVB exposure [97].
Photoallergic reactions are typically pruritic, eczematous eruptions in sun-exposed areas of skin that develop 24 to 48 hours after sun exposure [64]. Occasionally, photoallergic contact dermatitis may become persistent and evolve into chronic actinic dermatitis (CAD), even after the offending drug or chemical has been discontinued. (See 'Chronic actinic dermatitis' above.)
Photoallergic reactions occur in most instances after exposure to topical rather than systemic agents (picture 8) [97-99].
The most common topical agents responsible for photoallergic reactions are [64,72,96,98,99,107,108]:
●Sunscreens (eg, benzophenones, cinnamates, avobenzone, dibenzoylmethanes)
●NSAIDs (eg, ketoprofen, diclofenac)
●Fragrances (eg, 6-methylcoumarin, musk ambrette, sandalwood oil)
●Phenothiazines (eg, promethazine, available in Europe as topical antihistamine)
●Antimicrobial agents (eg, bithionol, dichlorophene, chlorhexidine, hexachlorophene, triclosan, fenticlor)
Systemic medications that can induce photoallergic reactions include [72]:
●Quinolones
●Sulfonamides
Diagnosis — A thorough history regarding photosensitivity and a full skin examination are essential to accurately diagnose phototoxicity or photoallergy. At times, this can be due to obscure contact. For example, photoallergic contact dermatitis can occur through contact with photoallergens left on swimming goggles or in wristbands [109,110]. If the diagnosis remains uncertain, phototesting and/or photopatch testing are useful. Minimal erythema doses (MEDs) are decreased in patients with phototoxicity or photoallergy secondary to a systemic agent [111]. Photopatch testing identifies patients with photoallergic contact dermatitis.
In phototoxic reactions, histopathologic findings include ballooning of keratinocytes with scattered apoptotic keratinocytes (sunburn cells), variable spongiosis, and a mild or moderate superficial inflammatory cell infiltrate in the dermis. In severe reactions, epidermal necrosis may be seen.
In photoallergic reactions, histopathologic findings are similar to those of allergic contact dermatitis. Spongiosis, mild acanthosis, and a superficial perivascular lymphocytic infiltrate with eosinophils are usually seen [16]. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Diagnostic studies'.)
Treatment — For both phototoxic and photoallergic reactions, the offending drug or chemical causing exogenous photosensitivity should be discontinued whenever possible. Sun-protective measures such as sun avoidance, sun-protective clothing, and sunscreen are essential. Photosensitivity due to exogenous agents is often greatest in the long-wave UVA range. Broad-spectrum sunscreens that offer adequate UVA protection are indicated. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Photoprotection'.)
Most phototoxic reactions can be treated as sunburn (see "Sunburn"). Symptomatic treatment with cool compresses, emollients, and oral analgesics usually suffice. Topical anesthetics should be avoided because of the possibility of a contact allergy.
Photoallergic reactions should be treated in a manner similar to contact allergy. Specifically, application of topical corticosteroids to the involved areas will reduce pruritus and the inflammatory response. In some instances, a two- to three-week course of systemic corticosteroids may be necessary.
PHOTOSENSITIVITY DUE TO ENDOGENOUS AGENTS
Porphyria — The porphyrias are metabolic disorders caused by altered activities of one of the eight enzymes involved in heme biosynthesis. Several types of porphyria exhibit photosensitivity as a clinical manifestation. Examples include porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, congenital erythropoietic porphyria, hereditary coproporphyria, and hepatoerythropoietic porphyria. The pathogenesis, clinical manifestations, diagnosis, and treatment of the porphyrias are discussed separately. (See "Porphyrias: An overview".)
Smith-Lemli-Opitz syndrome — Smith-Lemli-Opitz syndrome is a rare, congenital, multiple anomaly syndrome caused by an inborn error of cholesterol metabolism due to deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase [112]. There is an associated photosensitivity that appears to be ultraviolet A (UVA) mediated in more than 50 percent of cases [113,114]. The relationship of abnormal cholesterol metabolism to photosensitivity remains unclear.
PHOTOEXACERBATED DERMATOSES — Photoexacerbated dermatoses are disorders that are exacerbated by sun exposure. Two well-known examples are lupus erythematosus and dermatomyositis.
Lupus erythematosus — Cutaneous manifestations of lupus erythematosus, which may be initiated or exacerbated by ultraviolet (UV) radiation, include acute cutaneous lupus, subacute cutaneous lupus, and discoid lupus. The UV wavelength that provokes the skin lesions in lupus is ultraviolet A (UVA) in some individuals, in others it is ultraviolet B (UVB), and in still others it is both UVA and UVB [115].
UV irradiation of skin causes transfer of Ro (SSA) and La (SSB) antigens from an intracellular location to the cell surface, which makes them accessible to the corresponding antibodies. It also stimulates production of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL) 6, IL-1-beta, and interferon (IFN) 1 [116].
Acute cutaneous lupus is seen in patients with systemic lupus erythematosus (SLE) and classically affects the malar area. Subacute cutaneous lupus may be associated with SLE but may occur without systemic involvement. Subacute cutaneous lupus is manifested as photo-distributed scaly erythematous psoriasiform papules and plaques, which at times may have an annular appearance. Discoid lupus is sometimes clearly photosensitive. However, the frequent occurrence of discoid lesions on the relatively sun-protected scalp and conchal bowl of the ears is evidence against a strict requirement of sun exposure for discoid lesions to form. However, discoid lupus lesions have been produced experimentally by repeated exposure to UV radiation [115,117].
A more comprehensive discussion of cutaneous lupus is presented separately. (See "Overview of cutaneous lupus erythematosus".)
Drug-induced subacute cutaneous lupus — Drug-induced subacute cutaneous lupus erythematosus (SCLE) presents with a photosensitive cutaneous eruption identical to idiopathic SCLE [118]. Among the medications reported to induce subacute cutaneous lupus, terbinafine, thiazide diuretics, and calcium channel blockers are more frequently involved [119,120]. (See "Drug-induced lupus".)
Dermatomyositis — The cutaneous findings associated with dermatomyositis are often induced by UV radiation and appear on sun-exposed skin. Classic skin findings include a heliotrope rash on the face, erythematous papules overlying dorsal proximal interphalangeal joints (Gottron's papules), and scaly violaceous erythema in a "shawl distribution" (ie, a diffuse violaceous erythema over the back and shoulders) and on the "v"-area of the chest. Approximately 50 percent of dermatomyositis patients have a diminished minimal erythema dose (MED) response to UVB radiation [121]. (See "Clinical manifestations of dermatomyositis and polymyositis in adults" and "Juvenile dermatomyositis and other idiopathic inflammatory myopathies: Epidemiology, pathogenesis, and clinical manifestations".)
Pellagra — Pellagra is caused by a deficiency of vitamin B3 (niacin) [122]. A dietary basis for niacin deficiency is rarely responsible for pellagra in the United States because it has been incorporated into enriched preparations of flour. However, dietary deficiency of niacin does still occur in other countries, particularly those with a high dietary content of corn. When pellagra is diagnosed in the United States, it is usually a consequence of alcoholism, bariatric surgery, malabsorption syndromes, or certain drugs (isoniazid, ethionamide, chloramphenicol, 6-mercaptopurine, fluorouracil, azathioprine, and phenobarbital). Because tryptophan is a precursor of niacin, disorders such as carcinoid syndrome and Hartnup disease may also have clinical features of niacin deficiency. (See "Clinical features of carcinoid syndrome".)
Clinical manifestations include a photosensitive dermatitis, diarrhea, and dementia (also called the three Ds). The skin rash presents as an erythema in sun-exposed areas that progresses to hyperpigmentation and scaling (picture 9). A characteristic feature of the disease is Casal's necklace, which is a ring of erythema and hyperpigmentation extending around the neck onto the chest (picture 10). Based on phototesting of a single patient, UVA wavelengths are thought to provoke the rash [123].
Other — Reports of cases of photoexacerbation exist for a number of other diseases, including [72]:
●Acne
●Atopic dermatitis
●Bullous pemphigoid
●Carcinoid syndrome
●Cutaneous T cell lymphoma
●Disseminated superficial actinic porokeratosis
●Erythema multiforme
●Familial benign chronic pemphigus (Hailey-Hailey disease)
●Hartnup disease
●HIV infection
●Keratosis follicularis (Darier disease)
●Lichen planus
●Pemphigus, including pemphigus foliaceus (erythematosus)
●Pityriasis rubra pilaris
●Psoriasis
●Reticular erythematous mucinosis
●Rosacea
●Seborrheic dermatitis
●Toxic epidermal necrolysis (TEN)
●Transient acantholytic dermatoses (Grover's disease)
●Viral infections, including herpes simplex
●Viral exanthems
RARE GENODERMATOSES — Photosensitivity is a manifestation of several genodermatoses with DNA repair defects or chromosomal instability. These include xeroderma pigmentosum, Bloom syndrome, Cockayne syndrome, trichothiodystrophy, and Rothmund-Thomson syndrome. Skin cancer, cutaneous poikiloderma, short stature, craniofacial defects, intellectual impairment, or skeletal defects present at an early age may suggest one of these syndromes. (See "Xeroderma pigmentosum" and "Bloom syndrome" and "The genodermatoses: An overview", section on 'Disorders with malignant potential'.)
Kindler epidermolysis bullosa, another photosensitive genodermatosis, is characterized by acral bullae and skin fragility, among other features. The syndrome is caused by a loss-of-function mutation in FERMT1, which encodes a membrane-associated structural signaling protein [124]. (See "Kindler epidermolysis bullosa".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Photosensitivity disorders (photodermatoses)".)
SUMMARY AND RECOMMENDATIONS
●Definition and classification – Photosensitivity disorders of the skin are conditions in which an abnormal cutaneous response occurs after exposure to ultraviolet (UV) radiation or visible light. The major categories of photosensitivity disorders include idiopathic photodermatoses, photodermatoses due to exogenous or endogenous agents, photoexacerbated dermatoses, and photosensitive genodermatoses. A table describing the key features of many of the photosensitive disorders is provided (table 1). (See 'Introduction' above.)
●Idiopathic photodermatoses – The idiopathic photodermatoses are photosensitive disorders, many of which may be immunologically mediated, although the inciting agents are unknown. These include polymorphous light eruption (PMLE), actinic prurigo, hydroa vacciniforme, chronic actinic dermatitis (CAD), and solar urticaria (see 'The idiopathic photodermatoses' above):
•Polymorphous light eruption – Polymorphous light eruption (PMLE), the most common idiopathic photodermatosis, and juvenile spring eruption, a PMLE variant, are reviewed separately. (See "Polymorphous light eruption".)
•Actinic prurigo – Actinic prurigo is a childhood-onset pruritic photo-induced eruption most common in Mestizos (ie, individuals of mixed American Indian and European ancestry). Sun protection is an important component of therapy. For all patients with actinic prurigo, we suggest the use of topical corticosteroids as initial therapy (Grade 2C). For patients with moderate to severe disease who do not improve with sun protection and topical corticosteroids, we suggest treatment with prophylactic phototherapy, given initially with a short course of oral corticosteroids (Grade 2C). For patients with extensive or resistant disease, we suggest treatment with thalidomide (Grade 2C). (See 'Actinic prurigo' above.)
•Chronic actinic dermatitis – Chronic actinic dermatitis (CAD) is a persistent photodistributed eczematous eruption often seen in older males. Treatment should include sun-protective measures, emollients, and avoidance of inciting agents, if a contact or photocontact allergy is present. We suggest the use of high-potency topical corticosteroids and/or topical tacrolimus as needed for active dermatitis (Grade 2C). Refractory cases can benefit from treatment with systemic immunosuppressants or psoralen plus ultraviolet A (PUVA) initially given with oral glucocorticosteroids. (See 'Chronic actinic dermatitis' above.)
●Phototoxic reactions – Phototoxic reactions resemble an exaggerated sunburn and result from direct tissue or cellular damage following exposure to a phototoxic agent and UV radiation. Most drug-induced photosensitivity reactions are phototoxic. Plant furocoumarins and tar also cause phototoxicity. Phototesting is useful for diagnosis. (See 'Phototoxicity' above and 'Diagnosis' above.)
●Photoallergic reactions – A photoallergic reaction is a form of allergic contact dermatitis in which a photosensitizing chemical or drug once activated by UV radiation serves as the allergen and elicits an eczematous reaction in a sensitized individual. Most photoallergic reactions are caused by topical agents, rather than systemic medications. Phototesting and photopatch testing are useful for diagnosis. (See 'Photoallergy' above and 'Diagnosis' above.)
●Porphyrias – The porphyrias are metabolic disorders caused by altered activities of one of the eight enzymes involved in heme biosynthesis. Several types of porphyria exhibit photosensitivity as a clinical manifestation. These include porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, congenital erythropoietic porphyria, hereditary coproporphyria, and hepatoerythropoietic porphyria. The pathogenesis, clinical manifestations, diagnosis, and treatment of the porphyrias are discussed separately. (See "Porphyrias: An overview".)
●Photoexacerbated dermatoses – Photoexacerbated dermatoses are diseases that are exacerbated by sun exposure, such as lupus erythematosus and dermatomyositis. (See 'Photoexacerbated dermatoses' above.)
●Genodermatoses associated with photosensitivity – Photosensitivity is a manifestation of several genodermatoses. Examples include xeroderma pigmentosa, Bloom syndrome, Cockayne syndrome, trichothiodystrophy, Rothmund-Thomson syndrome, and Kindler epidermolysis bullosa. (See 'Rare genodermatoses' above.)
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