*In particular, is characteristic for PLE and solar urticaria

 

 

 

Polymorphic light eruption

 

Salient features

·        Polymorphic light eruption is the most common photodermatosis with a female preponderance typically presenting in the spring.

·        Clinical presentation: A pruritic, erythematous, symmetrically distributed eruption of variable interindividual morphology (in most cases papular) on sun-exposed skin areas, within hours to days of exposure, with full resolution in several days.

·        Histopathology: Epidermal spongiosis with a superficial and deep dermal, perivascular, mixed-cell infiltrate and papillary dermal edema.

·        Etiology and Pathogenesis: A resistance to ultraviolet (UV)-induced immune suppression with subsequent delayed-type hypersensitivity reaction against UV-induced antigen(s).

·        Prevention and Therapy: Responds to broad-spectrum sunscreen use, oral or topical steroids, and prophylactic low-dose immunosuppressive phototherapy.

 

Introduction

Polymorphic light eruption (PLE) is a common, idiopathic, acquired and acute recurrent, delayed‐onset, abnormal reaction to sunlight (or artificial UVR source) that resolves without scarring. There are several morphological variants, hence the term ‘polymorphic’.

It is probably a delayed-type hypersensitivity (DTH) reaction against an undefined photo induced endogenous cutaneous neo-antigen, as a result of genetically-impaired UVR-induced suppression of the induction phase of the reaction.

 

 

Epidemiology

 

Females are affected two to three times more often than males, with the second and third decades being the most common times of onset. The pathogenesis is unknown, but a family history may be elicited in between 10% and 50% of patients. It has been reported by some investigators that 10–20% of patients with PLE may have positive antinuclear antigens (ANAs) and a family history of lupus erythematosus. Photosensitive systemic lupus erythematosus (SLE) patients may give a history of PLE-like eruptions for years before the diagnosis of SLE is made. PLE patients should be followed for the development of symptoms of SLE.

 

Pathogenesis

Attacks of PMLE are produced by exposure to UVR (and perhaps, on occasion, visible light) from sunlight or other artificial sources such as tanning beds. Broadly speaking, perhaps about a quarter of patients are sensitive to just UVB, a quarter to both UVB and UVA, and a half to just UVA.

Immune resistance to UVR in PMLE

(A) UVR hits a molecule in the skin that leads to the formation of a photo antigen. In patients with PMLE, an immune response is mounted against such a photo antigen that results in the formation of PMLE.

(B) In healthy subjects, such an immune response is abrogated by simultaneous immune suppression induced by UVR. 

 

PMLE appears to represent a delayed-type hypersensitivity (DTH) response to as-yet-undefined, endogenous cutaneous, photo induced antigens.

It is not known what causes PLE. It may be an autoimmune disorder. Susceptibility to PMLE appears to be genetic. The inherited abnormality appears to be a resistance to the normal UVR-induced suppression of the induction phase, but not the elicitation, of cutaneous DTH responses. As a result, in PMLE, a lesser degree of cutaneous immunosuppression following UVR exposure (compared to normal individuals) results in a persistent ability to mount a DTH response against UVR-altered endogenous cutaneous molecules, leading to the development of clinical lesions. It has been postulated that the protection of normal human skin from UV induced photo allergens is due to the photo-immunosuppression phenomenon and this mechanism is disturbed in PMLE patients.  Possible underlying mechanisms include: (1) an under-expression of apoptotic-cell clearance genes in keratinocytes, thus prolonging antigen presence; and/or (2) inefficient free radical removal, thereby increasing photo antigen production. In fact UVR-induced cutaneous immunosuppression may protect against developing PMLE, but it can increase the risk of skin cancer; of note, PMLE patients appear to have a reduced tendency to develop such cancers.

 

Pathology

In most cases there is a superficial and deep, predominantly perivascular lymphohistiocytic dermal infiltrate, often with scattered eosinophils and neutrophils. Significant papillary dermal edema occurs commonly. The edema sometimes can be so extensive that it verges on subepidermal vesiculation. It has been suggested that an absence of dermal deposits of acid mucopolysaccharides may help distinguish it from LE. Some basal liquefaction may be present, but is not as marked as in LE. Spongiosis may be found, especially in papulovesicular PLE. Direct immunofluorescence is negative in PLE.

 

Predisposing factors

The occurrence of PLE is more frequent at higher latitudes. It is thought that previous greater sunlight exposure followed by more intermittent, less intense exposure might predispose to PLE development.

 

Clinical features

 

History

Within several hours to days, but usually not less than 30 minutes, after the first exposure to an intense dose of sunlight, usually in spring or early summer, itchy skin lesions of variable morphology appear on sun-exposed skin, as a delayed reaction. Patients may note itching as the first sign of an impending PMLE eruption. The threshold required to trigger PMLE varies from patient to patient and is usually from 30 minutes to several hours. The delay after exposure before onset is usually 6 or more hours. Often, the symptoms or rash are not noted until the evening or night after midday sunlight exposure, or not until the following day. It can also occur after recreational sunbed use. It is rare in winter except after extended outdoor recreational activities. Sufficient exposure may also occur through window glass. Many patients also suffer from flares for summer holidays.

Once UV exposure ceases, all lesions gradually resolve fully without scarring over several days, occasionally taking 7-10 days. As summer progresses, following repeated exposure to sunlight, many individuals show a hardening effect from the development of immunologic tolerance. Skin lesions are then less likely to occur or are less severe, permitting the individual to tolerate prolonged sun exposure. Occasionally, patients describe a longer duration. An unexplained, unusually prolonged rash lasting more than 3 weeks raises suspicion of LE.

 

Presentation

Affected sites

Polymorphic light eruption affects sunlight‐exposed sites exclusively. The occasional exceptions to this can be explained by UV transmission through clothing. Typically, some, but virtually never all, of the exposed skin is affected, particularly skin that is habitually covered during the winter, such as the upper chest, V area of the neck, upper arms and extensor forearms, are particularly affected, whereas areas exposed to sunlight all year (face and dorsa of hands) may be relatively spared, although not always, presumably due to tolerance induced by repeated perennial UVR exposure (‘hardening’ ­phenomenon).  However, lesions may occur on the face, if there has not been previous exposure to the sun. Lesions are basically symmetrically distributed, but frequently are grouped and patchy. The distribution pattern and type of lesions in a given patient are usually consistent over time. Typically affected sites are the bridge of the nose, malar areas of the cheeks, tip of the chin, sides and back of the neck, the V area of the chest, dorsa of the hands, dorsolateral aspects of the forearms, fronts and backs of the legs, and dorsa of the feet, but there may be more widespread involvement of sun-exposed sites. Facial involvement is more commonly seen in children with PLE. PLE is generally non‐scarring unless secondary excoriation is prominent.

Cutaneous Lesions

+

+

As the name of the condition implies, PMLE has many morphologic forms of skin lesions, all probably with similar pathogenesis and prognosis. The term “polymorphous” describes the variability in lesion morphology observed among different patients with the eruption.

Clinically, mildly to markedly pruritic, grouped, erythematous or skin-colored edematous papules of varying sizes, sometimes coalescing into large, smooth or unevenly surfaced plaques, are seen. In darkly pigmented individuals, the most common morphology is grouped, pinhead-sized papules in sun-exposed areas. Vesicles, bullae, papulovesicles, urticarial, confluent edematous swelling, insect bite-like, and erythema multiforme-like forms are additional manifestations. The papular and papulovesicular types are the most frequent. Rarely there is pruritus alone without a rash (‘sine eruptione’ with a typical time course but no visible eruption) and purpuric/haemorrhagic subtypes are rarely reported. PLE is often said to be monomorphic within individuals – it looks similar each time it occurs. However, some individuals have different morphologies on different sites, for example edematous plaques on the face and a papulovesicular eruption on the forearms.

Systemic symptoms in PMLE are rare, but headache, fever, chills, malaise and nausea may occur. These systemic symptoms may result from UV induced release of cytokines with pyogenic activity related to an accompanying sunburn reaction.

 

Juvenile springtime eruption

 

This is typically a recurrent blistering eruption affecting the upper pinnae of boys and young men occurring after a few days of intense sunlight exposure during spring and is characterized bypruritic papules and vesicles on their ear helices, although typical PMLE sometimes coexists.  It as a variant of PLE and is more common in males with short hair and prominent ears.

 

 

Complications and co‐morbidities

Patients with PLE may experience significant disease-related psychosocial morbidity. The rate of both anxiety and depression in patients with PLE are twice that of the general population, and these rates are similar to those observed in patients with psoriasis and atopic dermatitis.

A share pathogenesis for LE and PLE has been suggested. PLE lesions may precede the development of lupus, and progression of PLE to lupus has been proposed in some cases. However, the presence of autoantibodies does not portend development of LE.

A resistance to UV-induced immune suppression in PLE may be responsible for photo aggravation of other diseases, such as coexisting psoriasis. 

Sunscreen allergy and photo allergy can complicate PLE. Patients can be reassured that they are not at increased risk of developing skin cancers; in fact they have a lower skin cancer risk than people without PLE.

 

Differential diagnosis

It is usually straightforward to diagnose PLE.

Most important clinical differential diagnosis of polymorphic light eruption (characteristic)

·       Solar urticaria ( occurrence of weals on any sun-exposed body site within minutes after UV exposure and fading within hour)

·       Lupus erythematosus, especially subacute cutaneous lupus erythematous (delayed occurrence of skin lesions on sun exposed body site within 10 – 14 days or later after UV exposure and persisting for several weeks)

·       Erythropoietic protoporphyria (painful skin redness and swelling within minutes of sun exposure starting in early childhood)

·       Photo aggravated erythema multiforme (Photo distributed erythema multiforme-like skin lesions, often associated with herpes simplex virus infection)

 

 

Diagnostic algorithm for abnormal responses to ultraviolet radiation

 

Diagnosis

This is suggested by the history, clinical findings, negative circulating antinuclear antibodies and anti-Ro/SSA, -La/SSB antibodies, and normal blood, urinary and stool porphyrin concentrations.

 

EVALUATION OF PHOTOSENSITIVITY – POSSIBLE LABORATORY INVESTIGATIONS

·       Routine histology ·       Antinuclear antibodies ·       Anti-SSA/Ro, -SSB/La antibodies ·       Plasma porphyrins, followed by complete porphyrin profile if positive ·       Photo testing ·       Photo patch testing

 

Photo testing is done with both UVB and UVA. Test sites are exposed daily, starting with two MEDs of UVB and UVA, respectively, for 1 week to 10 days, using increments of the UV dose. In more than 50% of patients, a PMLE-like eruption will occur in the test sites.

 

Diagnostic criteria for PLE

·       Delayed occurrence of skin lesions after ultraviolet (UV) exposure (within hours to days; but not < 30 minutes)

·       Lesions persists several days after exposure (up to 10 days after cessation of UV exposure)

·       Monomorphous clinical presentation on sites of predilection (upper chest, extensor arms, with sparing of the face and hands)

 

Prognosis and Clinical Course

 

The course is chronic and recurrent. Although some patients may develop "tolerance" by the end of the summer, the eruption usually recurs the following spring and/or when the person travels to tropical areas in the winter. Spontaneous improvement or even cessation of eruptions occurs after years.

 

Treatment

First line

 

Sun avoidance and protective measures are sufficient for most mild/moderately affected people. Patients should avoid midday sun (11 am to 3 pm) and wear appropriate clothing (tightly woven fabrics), and apply high protection, broad-spectrum sunscreens correctly (thickly, evenly and frequently). It is critical that the sun blocks contain specific absorbers of long-wave UVA (zinc oxide and titanium dioxide). Sun blocks containing more than one of these agents are more effective. Since UVA is the most common triggering wavelength, good UVA coverage is critical. Most patients do not apply an adequate amount of sunscreen for it to be optimally effective. Derma Gard film can be applied to windows at home and in the car to block the transmission of nearly all UBV and UVA, while allowing visible light to be transmitted. Degradation does occur so it should be replaced every 5 years. These measures of photo protection are critical for all patients, since they are free of toxicity and reduce the amount and duration of other therapies required. Patient education is important in the management of this disease, and photo testing may be required to convince the patient that he/she is UV-sensitive. It will also determine the action spectrum.

 

The use of topical tacrolimus ointment at night or twice daily, combined with the above measures for sun avoidance and the use of sunscreens, controls many of these patients. At times topical steroids, frequently of super or high potency in several daily to weekly pulses, are necessary to control the pruritus and clear the eruption. Antihistamines (hydroxyzine) may be used for pruritus.

 

Second line

 

 

For more severe and frequently affected patients: Desensitization with phototherapy is done with prophylactic 2-3 times weekly NB-UBV. Treatment is initiated during the spring and an average 15 treatments (about 5 weeks) is usually sufficient to induce hardening for the summer. An initial starting dose of 50% of the MED for NB-UVB is recommended, with the dose then increased by 10–15% per treatment. Oral prednisolone ((0.5–1mg/kg/day) may be used during the initial 7-10 days of treatment with photo therapy to minimize photo exacerbation. Once hardening is achieved, patients are then asked to expose themselves to noonday sunlight between 10 AM and 2 PM for 15-20 minutes (without sunscreen) weekly for the remainder of sunny season to maintain the hardened state. However, some patients find that they do not need to intentionally seek sun exposure to maintain the hardening. About 80% of patients can be controlled with phototherapy. Treatments have to be given before the sunny season, be repeated each spring, but are usually not necessary for more than 3 or 4 years.

 

 

For very itchy, widespread eruptions, or if rash develops in spite of the above measures, brief oral steroid courses—prednisolone <0.5 mg/kg, usually given for 5–7 days.  

 

Experimental second line systemic therapies

 

Antimalarial drugs should be considered for patients who are not protected by sunscreens and do not respond to phototherapy. The onset of benefit is 3–6 weeks after the medication is initiated, and is best instituted in the late winter to prevent spring outbreaks. A 3-month trial (hydroxychloroquine 400 mg/day for the first month and 200 mg/day thereafter) has been effective in reducing rash. Although the risk of eye damage is slight, ophthalmologic examinations should be obtained periodically to monitor for antimalarial toxicity.

 

Oral omega-3 fatty acids have been suggested to be as moderately helpful in some patients.

Third line

 

In the most severe refractory cases, management with azathioprine, cyclosporine, or mycophenolate mofetil may be considered. If these agents are used in a patient considered to have PLE, an evaluation for chronic actinic dermatitis should be performed, as patients with PLE rarely require these agents.

 

 

Prevention

Sun blocks are not always effective but should be tried first in every patient. Oral beta carotene, 60 mg three times a day for 2 weeks, before going in the sun may be protective. Oral prednisone 20 mg/day given 2 days before and 2 days during exposure is a good prophylaxis. Also, intramuscular triamcinolone acetonide, 40 mg, will suppress an eruption when administered a few days before a trip to a sunny region.