Polymorphous light eruption

INTRODUCTION — Polymorphous light eruption (PMLE) is the most common idiopathic photodermatosis; it is sometimes called "sun poisoning" or "sun allergy." PMLE usually presents as a pruritic rash in sun-exposed areas hours to days after sun exposure and persists for several days before subsiding [1]. Juvenile spring eruption is a variant of PMLE. (See 'Juvenile spring eruption (polymorphous light eruption variant)' below.)

An overview of cutaneous photosensitivity and a review of other photodermatoses are presented separately. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection" and "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment".)

EPIDEMIOLOGY — Polymorphous light eruption (PMLE) occurs more frequently in temperate areas. Several studies have indicated that the prevalence of PMLE is directly related to latitude, ranging from approximately 1 percent in China to over 20 percent in some Northern European countries [2]. However, within Europe, a latitude gradient has not been shown to occur [3].

The onset of PMLE typically occurs within the first three decades of life, and a female preponderance is reported [4,5]. Individuals with lightly pigmented skin are the most commonly affected, although PMLE can develop in individuals of all ethnicities and skin types [6]. In a United States study, a greater proportion of Black people with photosensitivity disorders were diagnosed with PMLE compared with White people (74 versus 44 percent) [7]. PMLE is uncommonly reported among Hispanic people [8].

PATHOGENESIS — Both ultraviolet A (UVA) and ultraviolet B (UVB) radiation, and occasionally visible light, have been implicated in the development of polymorphous light eruption (PMLE) [9]. In most studies, a higher proportion of patients develops the disease in response to UVA than UVB [5]. The eruption may be influenced by the dose and frequency of the UV radiation as well as by the extent and site of irradiated skin [10]. PMLE occurring after exposure to ultraviolet C radiation generated from welding arcs has been reported [11]. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Phototesting'.)

Patients with PMLE appear to have a genetic susceptibility, as evidenced by increased concordance in monozygotic twins [12]. In addition, a positive family history is present in 15 to 46 percent of cases [13,14]. Genetic modeling of PMLE in families with photosensitivity disorders suggests a dominant mode of inheritance with low penetrance [15]. A case-control study found a negative association with the GSTP1 allele of glutathione-S-transferase [16], but a subsequent study was unable to confirm this finding [17]. Candidate gene analysis of interleukin (IL)-10, Fc fragment of IgG receptor (FCGR2A), selectin-E (SELE), intercellular adhesion molecule-1 (ICAM1), IL1A, IL1B, IL1RN, and tumor necrosis factor (TNF)-alpha has been inconclusive [18].

The higher prevalence and severity of PMLE among younger women suggests that hormonal factors may be involved in its pathogenesis [19]. In animal models, 17-beta-estradiol inhibits UV-induced immunosuppression through a dose-dependent reduction in the release of immunosuppressive IL-10 from UVB-irradiated keratinocytes [20].

PMLE has many features in common with delayed-type hypersensitivity (DTH) responses in the skin, suggesting that it may be a cell-mediated immune response to unknown cutaneous photo-induced antigen(s) [21]. Timed biopsy specimens taken after solar-simulated irradiation displayed perivascular infiltrates of CD4⁺ T lymphocytes within a few hours and CD8⁺ T lymphocytes within days [22]. Increased numbers of dermal and epidermal Langerhans cells and dermal macrophages were also noted. In addition, expression of selectin-E (CD62E), vascular cell adhesion molecule-1 (VCAM-1; CD106), and ICAM-1 (CD54) on endothelial cells and keratinocytes has been observed, further supporting the relationship between PMLE and DTH reactions [1].

In healthy individuals, exposure to ultraviolet radiation has a suppressive effect on T cell immune responses in the skin. There is evidence to suggest that in patients with PMLE, this immunosuppressive effect of UV does not occur [23-26]. It has been postulated that this abnormal response to UV exposure permits PMLE patients to develop an inflammatory response to an endogenous photo-induced antigen, which does not occur in the general population [1]. The photoantigen responsible for PMLE has not been identified.

Regulatory T cells (Tregs) may be involved in the lack of UV-induced immunosuppression seen in patients with PMLE. One study compared the number and function of Tregs in 19 healthy controls and 30 patients with PMLE before and after undergoing photohardening with narrowband (311 nm) UVB phototherapy [27]. Although there was no difference in the number of circulating Tregs between healthy subjects and PMLE patients before phototherapy, Tregs isolated from PMLE patients lacked the capacity to suppress effector T cell proliferation. After receiving photohardening therapy, PMLE patients showed a significant increase in the number of circulating Tregs and expression of FoxP3 mRNA, an indicator of increased suppressive function.

Studies have implicated the innate immune system as well. There are increased levels of the antimicrobial peptides psoriasin, HBD2, and LL37 in the UV-irradiated skin of individuals with PMLE compared with healthy controls [28].

Both UVA and UVB exposure alter the skin microbiome [29]. This observation has led to speculation that these alterations may stimulate the innate immune system in some individuals, thereby contributing to the pathogenesis of PMLE [30].

Genome-wide analyses have been conducted comparing PMLE patients with healthy controls [31,32]. PMLE subjects were found to have lower levels of genes associated with clearance of apoptotic keratinocytes. It has been proposed that defective clearance of apoptotic keratinocytes may result in the development of an autoantigen eliciting a UV-driven, cell-mediated immune response [32]. This hypothesis is supported by the demonstration of greater amounts of apoptotic keratinocytes in the epidermis of subjects with cutaneous lupus erythematosus or PMLE compared with healthy controls [33].

CLINICAL MANIFESTATIONS — The onset of polymorphous light eruption (PMLE) characteristically occurs in the spring and early summer. When it occurs in winter, it usually results from tanning bed exposure [34] or vacationing in a sunny climate [3]. There is individual variation in the amount of exposure required to elicit PMLE. Skin lesions typically appear within hours, although they sometimes occur days after sun exposure, and are accompanied by intense pruritus. The eruption lasts one to several days and then resolves if further sun exposure is avoided. Occasionally, PMLE persists for weeks. Lesions heal without scarring. A characteristic feature of PMLE is that it is most severe in the spring and early summer, moderates as the summer progresses, and resolves in the autumn or winter, only to recur the next spring.

Sites of predilection for PMLE are sun-exposed areas, including the upper chest, the "V" of the neck, the back of the arms, and occasionally shoulders and lower legs. The disease occurs more frequently in skin that has been covered in the winter [6]. The face and dorsal aspects of the hands are uncommon sites of PMLE, possibly because the hardening phenomenon has occurred from regular sun exposure [1] (see 'Photohardening' below). Lesions often recur in the same anatomic locations.

Several different types of skin lesions can occur in PMLE, but in a given individual the morphology is usually monomorphic and when there is a recurrence, lesions are usually identical to those observed during previous eruptions. Most commonly, patients present with pruritic, erythematous, or skin-colored papules or plaques in a symmetric distribution on sun-exposed skin (picture 1A-C). Papulovesicles, vesicles, bullae, or confluent edematous plaques (especially on the face) may also be seen. Less commonly, lesions resemble insect bites or erythema multiforme.

PMLE presenting as pinpoint papules (picture 1D), which may also involve the face and the perioral area, has been described in African American and South Asian individuals [35-37]. In addition, pruritus without a cutaneous eruption has been reported [38]. An eczematous form of PMLE does not exist, although eczematous changes can occur as a secondary response to rubbing and scratching. Another unusual variant presenting with pruritic papules and plaques localized to the elbows also has been reported [39].

Systemic symptoms of fever, chills, headache, and nausea are rare but may accompany PMLE. PMLE has a major impact on patients' lives. Compared with the general population, patients with PMLE are more likely to suffer from depression and anxiety, spend less time in outdoor activities, and take fewer vacations per year [40,41].

Skin hardening effect — Continued sun exposure may lead to increased tolerance to ultraviolet (UV) radiation and even to resolution of PMLE, a process referred to as "hardening." By mid-summer, many patients are clear of the rash due to this phenomenon. The mechanism underlying hardening is not well understood, but is likely due to the cumulative effect of repeated small amounts of UV radiation resulting in increased melanin production, thickening of the stratum corneum, and, possibly, normalization of cutaneous cell-mediated immune responses [42,43].

DIAGNOSIS — A diagnosis of polymorphous light eruption (PMLE) is usually based upon the clinical finding of a pruritic eruption of papules or plaques on exposed skin (picture 1A-C) and the patient's history of a similar eruption occurring in spring or early summer after sun exposure and gradually improving over the summer months. It is important to exclude other photosensitive skin conditions (table 1). (See 'Differential diagnosis' below.)

Skin biopsy may be helpful in some cases, particularly to exclude other disorders. Histologic findings for PMLE are nonspecific and require correlation with clinical presentation (picture 2). Focal epidermal spongiosis with focal lymphocyte exocytosis and a perivascular and periadnexal lymphohistiocytic infiltrate with occasional eosinophils and rare neutrophils may be seen. Papillary dermal edema, focal interface changes, and mild hydropic basal cell degeneration are present in more advanced lesions [44]. Direct immunofluorescence of skin biopsies is negative. At times, photopatch testing is necessary to exclude photoallergic contact dermatitis [45].

Phototesting for the assessment of the minimal erythema dose (MED) is usually normal in patients with PMLE. Provocative phototesting, which tests for the appearance of PMLE lesions after repeated UV exposure, may be used to assist with diagnosis. Provocative phototesting is performed by exposing the same area of the skin on the forearms or "V" of the neck to suberythemal doses of either ultraviolet A (UVA) or ultraviolet B (UVB) daily for four to five days. In over 60 percent of individuals with PMLE, this procedure will elicit clinical and histologic features characteristic of PMLE. (See "Overview of cutaneous photosensitivity: Photobiology, patient evaluation, and photoprotection", section on 'Diagnostic studies'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of polymorphous light eruption (PMLE) includes other photosensitivity disorders, which are summarized in the table (table 1) and discussed in detail separately. (See "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment".)

Distinguishing PMLE from actinic prurigo (picture 3), including the photosensitive rash seen in Native Americans and Mestizos (individuals of mixed American Indian and European ancestry), may be particularly difficult because of their overlapping clinical features. However, actinic prurigo occurs mainly in children and, in contrast with PMLE, tends to persist through the summer and may even extend into the winter months. (See "Photosensitivity disorders (photodermatoses): Clinical manifestations, diagnosis, and treatment", section on 'Actinic prurigo'.)

The earliest lesions of subacute cutaneous lupus erythematosus (picture 4) may resemble those of PMLE but are less pruritic. There is controversy as to whether patients with lupus erythematosus have a greater potential to have PMLE or whether the PMLE-like lesions are merely part of the photosensitive phenomenon observed in patients with lupus erythematosus.

MANAGEMENT

Preventive measures

Sun protection — Sun protection is the first-line preventive measure for patients with polymorphous light eruption (PMLE) and includes sun avoidance, sun-protective clothing, and sunscreens. Broad-spectrum sunscreens with both ultraviolet A (UVA) and ultraviolet B (UVB) protection and a sun protection factor (SPF) of at least 30 should be regularly and generously applied [46-49]. In one study of 15 patients with a history of PMLE, a broad-spectrum SPF 45 sunscreen applied at a dose of 2 mg/cm² prevented PMLE in all subjects after repeated exposure to UVA-UVB radiation [49]. (See "Selection of sunscreen and sun-protective measures".)

Products containing photostabilized avobenzone and/or ecamsule (table 2) offer improved protection against UVA, and have been effective in preventing PMLE eruptions [47-50]. Sunscreens that contain the non-micronized form of zinc oxide or titanium dioxide also offer photoprotection that extends throughout the UV and into the visible spectrum. (See "Selection of sunscreen and sun-protective measures", section on 'Spectrum'.)

Systemic photoprotection — There is insufficient evidence to suggest oral supplementation with carotenoids or antioxidants for the prevention of PMLE. In a small, randomized trial, 12-week oral supplementation with lycopene, beta-carotene, and Lactobacillus johnsonii was not effective in preventing PMLE [51]. In a small, uncontrolled study, a two-week course of oral supplementation with Polypodium leucotomos, a natural extract of a tropical fern with anti-inflammatory and antioxidant properties, prevented the development of a response to UVA and UVB irradiation in approximately one-third of the patients [52].

Afamelanotide, a synthetic analogue of alpha-melanocyte stimulating hormone that promotes skin tanning used for the prevention of phototoxic reactions in patients with erythropoietic protoporphyria, may be a potential prophylactic treatment for patients with PMLE [53,54]. However, data from an industry-sponsored phase III trial have not been published.

Photohardening — Prophylactic phototherapy with low-dose PUVA (psoralen plus UVA) or broadband or narrowband UVB in early spring to induce tolerance to sun exposure may be an option for patients who are expected to develop significant symptoms during the spring or summer [55-58]. Treatments are usually given at suberythemal doses two to three times per week over four to six weeks.

The use of prophylactic phototherapy for PMLE is supported by a limited number of small randomized trials [56-59]. In one study, treatment was successful in 92 percent of patients treated with PUVA and 62 percent of patients treated with broadband UVB [58]. Other studies have shown narrowband UVB to be as effective as PUVA [56,57]. Because narrowband UVB is easier to administer, it is often preferred to PUVA therapy for patients with PMLE. Narrowband UVB phototherapy can be administered three times per week, starting with a dose equivalent to 50 to 70 percent of the minimal erythema dose (MED). The dose is increased during subsequent treatments as tolerated by the patient. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy" and "UVB phototherapy (broadband and narrowband)".)

Exacerbations may occur early in the course of phototherapy. If these occur, potent topical corticosteroids (groups 1 to 3) (table 3) or a short course of oral glucocorticoid therapy (eg, prednisone 0.5 mg/kg for five to seven days) may be required [55,60]. (See 'Treatment' below.)

Other — The 1,25-dihydroxyvitamin D analogue calcipotriol has been investigated as a preventive agent in PMLE. In a randomized placebo-controlled intraindividual half-body trial involving 13 patients, calcipotriol cream significantly inhibited the severity of PMLE lesions on photoprovocation testing, suggesting that it may be of therapeutic benefit [61].

Treatment — Many patients with mild PMLE do not seek medical attention, and chronic sun exposure may eventually prevent eruptions via the "hardening" phenomenon. However, some patients may require treatment for symptomatic relief [55].

Patients with mild to moderate eruption — For patients with mild PMLE, we suggest topical corticosteroids for symptomatic treatment of skin inflammation and pruritus. Potent topical corticosteroids (groups 1 to 3) (table 3) are applied once or twice daily on the affected areas for five to seven days. Facial lesions should be treated with lower-potency topical corticosteroids (groups 6 to 7). Oral antihistamines may be useful to control pruritus. (See "Pruritus: Therapies for localized pruritus".)

The efficacy of topical corticosteroids for PMLE has not been evaluated in randomized trials. Their use is based upon clinical experience and evidence of efficacy in other inflammatory skin conditions [1].

Patients with severe eruption — Patients with acute episodes of PMLE may require a short course of oral corticosteroids. Prednisolone 25 mg or prednisone 30 mg can be given for four to five days. Slightly longer treatment courses may be required in some cases. However, frequent courses of systemic corticosteroids are not recommended due to associated potential side effects. (See "Major adverse effects of systemic glucocorticoids".)

In one trial, 21 patients with PMLE were given a seven-day supply of both prednisolone 25 mg and placebo tablets prior to a sunny vacation [62]. The order of administration had previously been randomized by a computer-generated sequence. If patients noted improvement, the initial treatment was continued until symptoms resolved or for a maximum of seven days. Patients were instructed to switch to the other therapy if no improvement occurred after 48 hours. Treatment with prednisolone reduced the mean time to resolution of itch (2.8 versus 5.4 days) and rash (4.2 versus 7.8 days).

Antimalarials are used for the treatment of some photosensitive disorders, including cutaneous lupus erythematosus, porphyria cutanea tarda, and dermatomyositis. Small randomized trials have demonstrated improvement in PMLE with antimalarials [63,64]. There are isolated reports of successful use of azathioprine and cyclosporine for the treatment of severe, recalcitrant PMLE [65,66].

PROGNOSIS — Polymorphous light eruption (PMLE) is a recurrent condition that may persist for years. However, the severity often improves with time. In a follow-up study of 114 patients with PMLE, 57 percent of patients noted decreasing sun sensitivity over the course of seven years, including 12 patients (9 percent) who reported complete resolution [67].

JUVENILE SPRING ERUPTION (POLYMORPHOUS LIGHT ERUPTION VARIANT) — The term "juvenile spring eruption" was first proposed in 1954 for a recurrent springtime eruption on the ears of young boys [68]. This disorder was found to affect approximately 7 percent of school-aged children in New Zealand [69]. A family history may be positive in some cases [70].

Patients often present in childhood or early adolescence, but initial presentation in young adulthood has also been reported [71,72]. The lesions are typically erythematous scaly papules or bullae. They occur on the ears (picture 5A-B), face, and dorsal hands.

Onset occurs in the spring, and symptoms resolve within several weeks, not to recur until the following spring. Boys are more commonly affected than girls. It has been postulated that this is related to shorter haircuts that expose their ears.

The diagnosis is typically made on a clinical basis. The differential diagnosis includes herpes simplex viral (HSV) infection and hydroa vacciniforme. Viral cultures may be performed to rule out HSV, but the bilateral localization of juvenile spring eruption is uncommon in HSV infection. Predominantly vesicular lesions that heal with scarring and the lack of predilection for the ears are features more characteristic of hydroa vacciniforme.

Treatment of juvenile spring eruption is not always necessary due to the transient nature of the disease. Topical corticosteroids may be effective to reduce inflammation. It is important to emphasize sun protection.

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

●Epidemiology – Polymorphous light eruption (PMLE) is the most common idiopathic photodermatosis. The prevalence of PMLE is higher in temperate regions and seems to increase with latitude. Disease onset usually occurs during the first three decades. Individuals with fair skin are more likely to develop the disorder. (See 'Epidemiology' above.)

●Pathogenesis – Ultraviolet A (UVA) is the most common inciting spectrum of light, but ultraviolet B (UVB) and visible light may also provoke PMLE in some patients. (See 'Pathogenesis' above.)

●Clinical presentation – PMLE is characterized by pruritic papules, papulovesicles, or plaques that appear hours or days after sun exposure and persist for days (picture 1A-D). Systemic symptoms are rare. Continued sun exposure characteristically leads to suppression of the condition over time. (See 'Clinical manifestations' above.)

●Diagnosis – Diagnosis is primarily based upon the patient's history and physical findings. In some cases, skin biopsy or provocative phototesting may also be indicated. The differential diagnosis includes lupus erythematosus, erythropoietic protoporphyria, and solar urticaria (table 1). (See 'Diagnosis' above.)

●Management – The management of PMLE includes preventive measures such as sun avoidance, sun-protective clothing, sunscreen, and treatment of symptoms. Broad-spectrum sunscreens with a sun protection factor (SPF) of at least 30 should be regularly used. (See 'Preventive measures' above.)

•For patients who develop frequent exacerbations during the spring and summer, we suggest prophylactic phototherapy in early spring (Grade 2B). (See 'Photohardening' above.)

•For patients with mild active lesions, we suggest treatment with potent topical corticosteroids (groups 1 to 3 (table 3)) (Grade 2C). Oral antihistamines may be useful to control pruritus. Patients with acute episodes of PMLE may require a short course of oral corticosteroids. (See 'Treatment' above.)

●Juvenile spring eruption – Juvenile spring eruption is a variant of PMLE that is manifested by erythematous papules or bullae typically on ears of children or adolescents after sun exposure (picture 5A-B). Symptoms are self-limited and resolve within several weeks. (See 'Juvenile spring eruption (polymorphous light eruption variant)' above.)