What Caused These Papules?

Patient Presentation

An otherwise healthy 35-year-old Caucasian woman presented with a pruritic eruption on the neck, upper chest and extremities. This was the third consecutive summer in which she developed a similar eruption. Her rash peaked within several weeks and resolved without treatment or change in activity after 6 weeks. No history of atopy was elicited, nor any family history of similar eruptions. She denied the use of any new medications. On physical examination there were multiple, small, symmetric erythematous papules distributed on the neck, the V of the chest, arms and ankles.

What is Your Diagnosis?

Diagnosis: Polymorphous Light Eruption

Polymorphous light eruption (PMLE) is a chronic idiopathic photodermatosis characterized by recurrent, abnormal, delayed reactions to sunlight. Various morphologic subtypes have been described, including papular and papulovesicular forms, eczematous reactions, plaque and nodular forms, as well as erythema multiforme-like lesions.^1-4 In any given patient, however, usually one clinical form predominates.^1-5 The term polymorphous light eruption was introduced by Rasch in 1900, whose definition encompassed several pruritic urticarial, eczematous, papular and vesicular reactions to sunlight.^1-5 Subsequently, Haxthausen noted that two distinct clinical forms could occur simultaneously or in sequence.² Currently, disagreement exists concerning the precise clinical features defined by the term PMLE,^2-4 and satisfactory methods for differentiating PMLE from lesions caused by other light-induced and photosensitive diseases are needed.^2-3 More About PMLE PMLE most commonly manifests during early adulthood, usually before the age of 30, but may occur in any age group.^1-3 In American Indian and Scottish populations, the disease tends to begin more often during childhood.² PMLE affects roughly 10% to 20% of the population in the United States, England and Ireland,⁵ and has a higher familial incidence in North and Latin American Indians, as well as in Finnish patients, in whom inheritance appears to be autosomal-dominant with reduced penetrance.^1,3 The disease occurs more frequently in fair-skinned individuals, but is not limited to either sex, nor to any particular racial or ethnic groups.^1,3 The four most frequently encountered morphologic variants of PMLE include a vesiculopapular eruption, a prurigo-like reaction, an eczematous eruption, and a macronodular form, but numerous other morphologies have been described.⁴ Overall, the most common variant of the eruption is that of small papules,^1,6 or vesiculopapules,⁴ which tend to be more pruritic⁴ and more photosensitive than other clinical forms.^2,7 The prurigo-like variant may occur more often in women, and the macronodular form more commonly in men,⁴ while the eczematous pattern of PMLE has been reported to develop at lower minimal erythema doses than the other types.¹ Different combinations of lesions may develop, but usually one dominant morphologic pattern is evident.^1-5 The age at onset may also be related to the particular clinical form,8 and may differ between the sexes.^8-9 A cell-mediated delayed-type hypersensitivity reaction has been suggested as a possible pathogenetic mechanism in PMLE.^2,3,10,11 The delayed onset of cutaneous findings coupled with a characteristic histologic pattern, as well as the appearance of lesions in areas distant from those initially involving the eruption, support this view.^2,10,11 Histologically, the T-lymphocyte has been identified as the predominant infiltrating cell, but the pattern of fibrin deposition differs from that observed in delayed-type hypersensitivity reactions.¹² Sunlight’s Effect in PMLE Sunlight exposure is the primary etiologic factor in the development of polymorphous light eruption, although genetic susceptibility may also play a role.² Numerous studies have reported conflicting data regarding the action spectra, minimal erythema doses, and energy requirements necessary to produce the lesions.^{1,3,6-7,9,13,14} Eruptions have been successfully reproduced using UVA, UVB, visible light,9 as well as ionizing radiation.² In response to UV light, epidermal cells in PMLE increase their capacity to stimulate peripheral blood mononuclear cells, which may implicate immune sensitization against skin antigens.¹⁵ The onset of the eruption is usually sudden, occurring in the early spring, but may also manifest during the summer, or in winter following sufficient sunlight exposure.² From as little as 10 minutes to several hours in the sun can precipitate an exacerbation of the disease, depending on the individual.⁸ Lesions are typically confined to sun-exposed areas of the body, most commonly the face, neck, upper chest and dorsal arms and hands, but have also been noted to develop over larger, more generalized areas due to autosensitization.^1,2,6 The most common symptom noted is pruritus, but burning and tenderness to touch may also be present, more frequently in patients with the macronodular variant.⁸ Other cutaneous symptoms include erythema, swelling, wheal and blister formation, as well as cheilitis and ocular sensitivity, which occur more commonly in Finnish and American Indian patients.^2,8 Many patients also experience nonspecific symptoms including malaise, headache, nausea and chills,⁸ and secondary cutaneous changes include scaling, hyperkeratosis and lichenification due to scratching.³ Maximal symptoms typically develop within 12 to 24 hours after sufficient exposure to sunlight, and the eruption itself usually resolves within 1 to 3 weeks without scarring.^3,8 During the course of the disease, sun sensitivity may increase, decrease or remain unchanged, and topographical changes in the distribution of involved skin may also occur.^1,8 Generally, PMLE follows a chronic pattern and increases in severity over time.² The “hardening phenomenon,” a modification of the patient’s response to sunlight after repeated exposures, has been observed in some patients, decreasing the severity of exacerbations and/or increasing tolerance to sunlight.^6,8

Histopathology

Epidermal changes seen on biopsy vary with the particular clinical variant of the disease. The small papular and eczematous forms demonstrate edema, spongiosis, vesicle formation, and frequent acanthosis and parakeratosis, while the large papular variant shows very little epidermal change.² Edema and mild liquefactive degeneration of the basal cell layer are visible with both morphologic forms.¹ Dermal changes are identical in each variant of PMLE, and include a dense perivascular lymphocytic infiltrate in the upper- and mid-dermis, along with edema in the upper dermis and blood vessel walls.² A CD4+ and CD8+ T-cell infiltrate is present as well.^2-3,10 Using direct immunofluorescence, intervascular fibrin deposition with less intense vascular and perivascular deposition is observed, which suggests that vascular injury with induction of the clotting cascade may be involved in the pathogenesis of the disease.¹² Staining for Ig and C3 has produced positive findings in a small percentage of PMLE lesions.⁷

Differential Diagnosis

The small papular and eczematous forms of PMLE can be confused with atopic dermatitis, hydroa vacciniforme, erythropoietic protoporphyria (EPP), airborne and nonairborne contact dermatitis, as well as photodermatitis. Differentiation from atopic dermatitis is most commonly made after elucidating any history of atopy, dependence on sunlight for lesion development, and by using phototests.¹ Hydroa vacciniforme and EPP can be differentiated clinically and by checking urine and stool porphyrin levels.^2,8 The most challenging entity to distinguish clinically from small papular or eczematous PMLE is allergic photocontact dermatitis, in which case phototesting is necessary.² The large papular and plaque morphologies of PMLE must be differentiated from the lymphocytic infiltrate of Jessner, lymphocytoma cutis, granuloma annulare, sarcoidosis, erythema multiforme, fixed drug eruptions and, most importantly, systemic lupus erythematosus (SLE). SLE may produce very similar (clinically and histologically) photosensitive lesions,^2-3,16 and also shares comparable phototesting characteristics with PMLE.¹ Direct and indirect immunofluorescence techniques are employed,^1,3 in addition to antinuclear antibody (ANA), anti-SSA, anti-SSB and anti-RO antibody tests.² An association of PMLE with LE has been proposed,³ but to date no progression to, or definite link with, SLE has been demonstrated.^2-3 Our patient’s laboratory evaluation included ANA, anti-SSA and anti-SSB levels, which were negative.

Management

No uniformly effective treatment for PMLE exists at present, but prophylactic measures including sunlight avoidance, protective clothing and sunscreen use are first-line therapies.^1-6 Sunscreens are more effective in preventing eruptions induced by UVB wavelengths than by UVA.¹³ Systemic beta-carotene has demonstrated limited benefit in treatment of PMLE,^2,14 but when combined with sunscreen it may be of additional efficacy.⁶ The antimalarials, chloroquine and hydroxychloroquine, are also effective treatments,¹⁷ particularly in less photosensitive patients, while topical corticosteroid therapy is of benefit during acute exacerbations.² Oral psoralen photochemotherapy (PUVA) has been shown to increase tanning, thicken the stratum corneum, and increase the erythema threshold in PMLE patients,^6,18 being especially effective in the prevention of UVA-provoked eruptions¹³ and in patients with very severe disease.¹⁹ These cutaneous alterations may produce a more effective barrier to sunlight, similar to the hardening phenomenon. Narrow-band TL-01 phototherapy has been shown to be as effective as PUVA treatment as a prophylactic measure,¹⁹ and UVB therapy has also demonstrated comparable results.⁹ Azathioprine (Imuran) may be useful in patients with severe disease recalcitrant to other forms of treatment,²⁰ while thalidomide has been reported to be a particularly effective therapy in American Indian patients.²

Acknowledgement: The authors would like to thank Dr. Eric Ehrsam for his assistance with this manuscript.

Patient Presentation

An otherwise healthy 35-year-old Caucasian woman presented with a pruritic eruption on the neck, upper chest and extremities. This was the third consecutive summer in which she developed a similar eruption. Her rash peaked within several weeks and resolved without treatment or change in activity after 6 weeks. No history of atopy was elicited, nor any family history of similar eruptions. She denied the use of any new medications. On physical examination there were multiple, small, symmetric erythematous papules distributed on the neck, the V of the chest, arms and ankles.

What is Your Diagnosis?

Diagnosis: Polymorphous Light Eruption

Polymorphous light eruption (PMLE) is a chronic idiopathic photodermatosis characterized by recurrent, abnormal, delayed reactions to sunlight. Various morphologic subtypes have been described, including papular and papulovesicular forms, eczematous reactions, plaque and nodular forms, as well as erythema multiforme-like lesions.^1-4 In any given patient, however, usually one clinical form predominates.^1-5 The term polymorphous light eruption was introduced by Rasch in 1900, whose definition encompassed several pruritic urticarial, eczematous, papular and vesicular reactions to sunlight.^1-5 Subsequently, Haxthausen noted that two distinct clinical forms could occur simultaneously or in sequence.² Currently, disagreement exists concerning the precise clinical features defined by the term PMLE,^2-4 and satisfactory methods for differentiating PMLE from lesions caused by other light-induced and photosensitive diseases are needed.^2-3 More About PMLE PMLE most commonly manifests during early adulthood, usually before the age of 30, but may occur in any age group.^1-3 In American Indian and Scottish populations, the disease tends to begin more often during childhood.² PMLE affects roughly 10% to 20% of the population in the United States, England and Ireland,⁵ and has a higher familial incidence in North and Latin American Indians, as well as in Finnish patients, in whom inheritance appears to be autosomal-dominant with reduced penetrance.^1,3 The disease occurs more frequently in fair-skinned individuals, but is not limited to either sex, nor to any particular racial or ethnic groups.^1,3 The four most frequently encountered morphologic variants of PMLE include a vesiculopapular eruption, a prurigo-like reaction, an eczematous eruption, and a macronodular form, but numerous other morphologies have been described.⁴ Overall, the most common variant of the eruption is that of small papules,^1,6 or vesiculopapules,⁴ which tend to be more pruritic⁴ and more photosensitive than other clinical forms.^2,7 The prurigo-like variant may occur more often in women, and the macronodular form more commonly in men,⁴ while the eczematous pattern of PMLE has been reported to develop at lower minimal erythema doses than the other types.¹ Different combinations of lesions may develop, but usually one dominant morphologic pattern is evident.^1-5 The age at onset may also be related to the particular clinical form,8 and may differ between the sexes.^8-9 A cell-mediated delayed-type hypersensitivity reaction has been suggested as a possible pathogenetic mechanism in PMLE.^2,3,10,11 The delayed onset of cutaneous findings coupled with a characteristic histologic pattern, as well as the appearance of lesions in areas distant from those initially involving the eruption, support this view.^2,10,11 Histologically, the T-lymphocyte has been identified as the predominant infiltrating cell, but the pattern of fibrin deposition differs from that observed in delayed-type hypersensitivity reactions.¹² Sunlight’s Effect in PMLE Sunlight exposure is the primary etiologic factor in the development of polymorphous light eruption, although genetic susceptibility may also play a role.² Numerous studies have reported conflicting data regarding the action spectra, minimal erythema doses, and energy requirements necessary to produce the lesions.^{1,3,6-7,9,13,14} Eruptions have been successfully reproduced using UVA, UVB, visible light,9 as well as ionizing radiation.² In response to UV light, epidermal cells in PMLE increase their capacity to stimulate peripheral blood mononuclear cells, which may implicate immune sensitization against skin antigens.¹⁵ The onset of the eruption is usually sudden, occurring in the early spring, but may also manifest during the summer, or in winter following sufficient sunlight exposure.² From as little as 10 minutes to several hours in the sun can precipitate an exacerbation of the disease, depending on the individual.⁸ Lesions are typically confined to sun-exposed areas of the body, most commonly the face, neck, upper chest and dorsal arms and hands, but have also been noted to develop over larger, more generalized areas due to autosensitization.^1,2,6 The most common symptom noted is pruritus, but burning and tenderness to touch may also be present, more frequently in patients with the macronodular variant.⁸ Other cutaneous symptoms include erythema, swelling, wheal and blister formation, as well as cheilitis and ocular sensitivity, which occur more commonly in Finnish and American Indian patients.^2,8 Many patients also experience nonspecific symptoms including malaise, headache, nausea and chills,⁸ and secondary cutaneous changes include scaling, hyperkeratosis and lichenification due to scratching.³ Maximal symptoms typically develop within 12 to 24 hours after sufficient exposure to sunlight, and the eruption itself usually resolves within 1 to 3 weeks without scarring.^3,8 During the course of the disease, sun sensitivity may increase, decrease or remain unchanged, and topographical changes in the distribution of involved skin may also occur.^1,8 Generally, PMLE follows a chronic pattern and increases in severity over time.² The “hardening phenomenon,” a modification of the patient’s response to sunlight after repeated exposures, has been observed in some patients, decreasing the severity of exacerbations and/or increasing tolerance to sunlight.^6,8

Histopathology

Epidermal changes seen on biopsy vary with the particular clinical variant of the disease. The small papular and eczematous forms demonstrate edema, spongiosis, vesicle formation, and frequent acanthosis and parakeratosis, while the large papular variant shows very little epidermal change.² Edema and mild liquefactive degeneration of the basal cell layer are visible with both morphologic forms.¹ Dermal changes are identical in each variant of PMLE, and include a dense perivascular lymphocytic infiltrate in the upper- and mid-dermis, along with edema in the upper dermis and blood vessel walls.² A CD4+ and CD8+ T-cell infiltrate is present as well.^2-3,10 Using direct immunofluorescence, intervascular fibrin deposition with less intense vascular and perivascular deposition is observed, which suggests that vascular injury with induction of the clotting cascade may be involved in the pathogenesis of the disease.¹² Staining for Ig and C3 has produced positive findings in a small percentage of PMLE lesions.⁷

Differential Diagnosis

The small papular and eczematous forms of PMLE can be confused with atopic dermatitis, hydroa vacciniforme, erythropoietic protoporphyria (EPP), airborne and nonairborne contact dermatitis, as well as photodermatitis. Differentiation from atopic dermatitis is most commonly made after elucidating any history of atopy, dependence on sunlight for lesion development, and by using phototests.¹ Hydroa vacciniforme and EPP can be differentiated clinically and by checking urine and stool porphyrin levels.^2,8 The most challenging entity to distinguish clinically from small papular or eczematous PMLE is allergic photocontact dermatitis, in which case phototesting is necessary.² The large papular and plaque morphologies of PMLE must be differentiated from the lymphocytic infiltrate of Jessner, lymphocytoma cutis, granuloma annulare, sarcoidosis, erythema multiforme, fixed drug eruptions and, most importantly, systemic lupus erythematosus (SLE). SLE may produce very similar (clinically and histologically) photosensitive lesions,^2-3,16 and also shares comparable phototesting characteristics with PMLE.¹ Direct and indirect immunofluorescence techniques are employed,^1,3 in addition to antinuclear antibody (ANA), anti-SSA, anti-SSB and anti-RO antibody tests.² An association of PMLE with LE has been proposed,³ but to date no progression to, or definite link with, SLE has been demonstrated.^2-3 Our patient’s laboratory evaluation included ANA, anti-SSA and anti-SSB levels, which were negative.

Management

No uniformly effective treatment for PMLE exists at present, but prophylactic measures including sunlight avoidance, protective clothing and sunscreen use are first-line therapies.^1-6 Sunscreens are more effective in preventing eruptions induced by UVB wavelengths than by UVA.¹³ Systemic beta-carotene has demonstrated limited benefit in treatment of PMLE,^2,14 but when combined with sunscreen it may be of additional efficacy.⁶ The antimalarials, chloroquine and hydroxychloroquine, are also effective treatments,¹⁷ particularly in less photosensitive patients, while topical corticosteroid therapy is of benefit during acute exacerbations.² Oral psoralen photochemotherapy (PUVA) has been shown to increase tanning, thicken the stratum corneum, and increase the erythema threshold in PMLE patients,^6,18 being especially effective in the prevention of UVA-provoked eruptions¹³ and in patients with very severe disease.¹⁹ These cutaneous alterations may produce a more effective barrier to sunlight, similar to the hardening phenomenon. Narrow-band TL-01 phototherapy has been shown to be as effective as PUVA treatment as a prophylactic measure,¹⁹ and UVB therapy has also demonstrated comparable results.⁹ Azathioprine (Imuran) may be useful in patients with severe disease recalcitrant to other forms of treatment,²⁰ while thalidomide has been reported to be a particularly effective therapy in American Indian patients.²

Acknowledgement: The authors would like to thank Dr. Eric Ehrsam for his assistance with this manuscript.