Spring and summer eruption of the elbows: A peculiar localized variant of polymorphous light eruption

Spring and summer eruption of the elbows: A peculiar localized variant of polymorphous light eruption Ana Mar
ıa Molina-Ruiz, MD,a Onofre Sanmart
ın, MD,c Carlos Santonja, MD,b Heinz Kutzner, MD,d and Luis Requena, MDa Madrid and Valencia, Spain; and Friedrichshafen, Germany Background: Polymorphous light eruption (PLE) is the most common form of idiopathic photodermatosis. Several morphologic variants of PLE have been described, including a localized form of PLE primarily affecting the helices of the ears. To our knowledge, the presence of lesions on the elbows as the unique manifestation of PLE has not yet been reported. We have studied 9 patients presenting with a recurrent eruption on the elbows, with clinical and histopathologic features indistinguishable from PLE, occurring during springtime. Recently, a peculiar eruption of the elbows, with similar clinical features to our patients, has been proposed as a manifestation of cutaneous lupus erythematosus. Objective: We sought to describe the clinical, histopathological, and immunohistochemical features of this peculiar eruption of the elbows. Methods: Nine patients presenting a recurrent spring eruption on the elbows, collected from April 1989 to June 2012, were retrospectively analyzed. We studied their clinical and histopathological features, and the immunophenotype of the infiltrate. Results: Five patients were men and 4 were women. The mean age was 44.7 years. The lesions consisted of pruriginous, erythematous-edematous papules and plaques, located on both elbows. The eruption appeared during the spring or early summer and recurred seasonally. No associated symptoms were present and the eruption regressed spontaneously or with topical corticosteroids after 7 to 15 days. Histopathologically, the lesions showed typical features of PLE, with variable degree of edema in the papillary dermis, and a papillary and reticular dermal perivascular infiltrate mostly composed of small lymphocytes. Immunohistochemical studies demonstrated strong immunoreactivity for CD2, CD4, and CD8, revealing the infiltrate was composed predominantly of T lymphocytes, with a predominance of T-helper over T-cytotoxic lymphocytes. Immunostaining for CD123 was negative, highlighting the absence of plasmacytoid dendritic cells. Other T- and B-cell markers, including CD30, PD-1, CXCL13, FoxP3, CD79a, and CD56 were also negative. Limitations: Retrospective case series design is a limitation. Phototests were not performed. Results of antinuclear antibodies were only available in 1 patient. Conclusions: We believe this recurrent eruption of the elbows represents a distinctive and localized variant of PLE rather than a peculiar manifestation of cutaneous lupus erythematosus and suggest the term ‘‘spring and summer eruption of the elbows’’ for this peculiar condition. The mechanism of this localization on the elbows, with sparing of other photoexposed areas, remains unknown. ( J Am Acad Dermatol 2013;68:306-12.) Key words: elbows; immunohistochemistry; lupus erythematosus; plasmacytoid dendritic cells; polymorphous light eruption.

From the Departments of Dermatologya and Pathology,b Fundaci
on Jim
enez D
ıaz, Madrid; Department of Dermatology, Fundaci
on Instituto Valenciano de Oncolog
ıac; and Dermatohistopathologisches Gemeinschaftslabor, Friedrichshafen.d Funding sources: None. Conflicts of interest: None declared.

306

Reprint requests: Luis Requena, MD, Department of Dermatology, Fundaci
on Jim
enez D
ıaz, Avd Reyes Cat
olicos 2, 28040 Madrid, Spain. E-mail: [email protected]. Published online November 21, 2012. 0190-9622/$36.00 Ó 2012 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2012.08.043

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Polymorphous light eruption (PLE) is the most women, with a mean age of 38 years (range 27-65 common photodermatosis and shows many moryears). All patients were of skin phototype III. phologic variants.1 Juvenile spring eruption, which Patients reported a pruritic sensation with variable primarily affects the helices of the ears in children in inflammatory lesions that appeared each year during springtime, is considered by several authors as a spring or early summer after the first week of sun localized variant of PLE.2 To our knowledge, the exposure and resolved in 1 to 2 weeks spontanepresence of lesions on the elbows as the only ously or with the use of topical corticosteroids. manifestation of PLE has not Characteristically, the lesions yet been described. Recently, recurred each year with the CAPSULE SUMMARY Bielsa et al3 reported a pecufirst sun exposure during liar eruption of the elbows, spring or early summer, and Polymorphous light eruption (PLE) is the with histopathology combinafter regression did not recur most common form of idiopathic ing changes of both cutaneduring autumn or winter, but photodermatosis. To our knowledge, the ous lupus erythematosus appeared again the next presence of lesions on the elbows as the (CLE) and interstitial granuspring or early summer with unique manifestation of PLE has not yet lomatous dermatitis. They the first exposure to sunlight. been reported. believe this eruption of the There were no associated We have studied 9 patients presenting elbows should be included systemic symptoms and no with a recurrent eruption on the elbows, within the spectrum of cutapatient reported a history of with clinical, histopathologic, and neous manifestations of luphotosensitivity. They deimmunohistochemical features pus erythematosus (LE). nied the use of any topical indistinguishable from PLE, occurring We have attended a series or systemic photosensitizers. during springtime. of patients presenting with a The clinical morphology recurrent spring and summer of the lesions and their evoWe believe this recurrent eruption of the eruption affecting the ellution was quite similar in all elbows represents a distinctive and bows. The clinical features cases (Table II). Diffuse erylocalized variant of PLE rather than a of our cases were similar to thema was the initial manipeculiar manifestation of cutaneous those reported by Bielsa festation, followed by the lupus erythematosus and suggest the et al,3 but our histopathologic appearance of multiple term ‘‘spring and summer eruption of and immunohistochemical edematous erythematous or the elbows’’ for this peculiar condition. findings support the notion violaceous papules of 1 to 5 that this peculiar eruption of mm in diameter (Fig 1, A and the elbows is better interpreted as a localized variant B), which coalesced to form erythematous plaques of PLE rather than a manifestation of CLE. We have with a symmetric distribution over the back of the given the name ‘‘spring and summer eruption of the elbows. The lesions were almost exclusively located elbows’’ to this striking dermatologic condition. on the elbows, with the exception of case 1, in which there also were some scattered erythematous papules on the sun-exposed areas of upper and lower METHODS extremities. Both elbows were symmetrically afNine patients presenting with a relapsing pruritic symmetric eruption of the elbows were attended at fected (Fig 1, A and B), except in patient 4, who the Department of Dermatology at Fundaci
on worked as a truck driver and presented more severe lesions on the left elbow, which was more exposed Jim
enez D
ıaz, Madrid, Spain. Patients 4 and 8 were to sunlight during his work hours (Fig 1, C ). In case referred from the Instituto Valenciano de Oncolog
ıa, 6, there were papulovesicles that grouped into Valencia, Spain. The clinical, histopathological, and bullous lesions surrounded by intense erythema immunohistochemical data of these cases were ret(Fig 1, D). The lesions resolved gradually within a rospectively analyzed. Antibodies used in this study period of 7 to 15 days, leaving mild hypopigmentaare listed in Table I. Antinuclear antibodies (ANAs) were assayed in 1 case using a standard indirect tion, but no scarring. immunofluorescence technique with commercially In all patients, complete routine laboratory investigations including hematologic and biochemical available Hep-2 cells. (glucose, hepatic, and renal parameters) tests disclosed no abnormalities. No phototests were perRESULTS formed. Patient 8 had positive ANAs, but the rest of Clinical features the patients were not tested for ANAs and no other Five patients were men, with a mean age of 50.2 serum immunologic tests were investigated. In 4 years (range 46-72 years) and 4 patients were d

d

d

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Abbreviations used: ANA: CLE: LE: PDC: PLE:

antinuclear antibodies cutaneous lupus erythematosus lupus erythematosus plasmacytoid dendritic cells polymorphous light eruption

patients the eruption regressed spontaneously after a variable period of 7 to 15 days. Five patients required treatment with topical corticosteroids and oral antihistamines because of intense pruritus. The patients were advised to exercise sun protection and use the appropriate broad-coverage sunscreens. They were followed up for several years (from 2-6 years) and 6 of them reported recurrences of the eruption each year during the spring or early summer, but no clinical features of systemic involvement or any other associated conditions were discovered. Histopathology and immunohistochemistry In 2 cases, the epidermis showed a range of changes from mild to moderate spongiosis, scale, crust, and parakeratosis. In the other 7 cases, the epidermis was not involved. There was variable, but generally moderate, edema of the papillary dermis, particularly in early lesions. All patients showed moderate to dense papillary and reticular dermal perivascular infiltrate composed predominantly of small lymphocytes (Fig 2). One case showed a lichenoid distribution of the inflammatory infiltrate, with the presence of scattered histiocytes in the infiltrate, slight epidermotropism of the lymphocytes, and almost total absence of dermal edema. Active interface dermatitis, with necrotic keratinocytes at dermoepidermal junction, was not a common feature, although in 2 cases there was focal and mild interface dermatitis with basal vacuolization. There was no evidence of granulomatous inflammation or mucin deposition in the dermis. Immunohistochemically, the inflammatory infiltrate of the lesions showed strong expression for CD2, CD4, and CD8, revealing the infiltrate was composed predominantly of T lymphocytes, with a higher proportion of CD4 than CD8 lymphocytes. CD68 (PGM-1) was focally positive, highlighting the presence of scattered histiocytes within the infiltrate. CD123 was negative, demonstrating the absence of plasmacytoid dendritic cells (PDCs) in these lesions. Immunostains for CD30, PD-1, CXCL13, FoxP3, CD79a, and CD56 were also negative (Fig 3).

DISCUSSION PLE is the most common form of idiopathic photodermatosis. It is a recurrent, acquired

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sunlight-induced rash of delayed onset appearing after exposure to ultraviolet radiation, mostly from the sun, in susceptible individuals. PLE is characterized clinically by the occurrence within hours to days of ultraviolet radiation exposure of nonscarring, pruritic, erythematous papules, papulovesicles, vesicles, or plaques on sun-exposed skin areas. The lesions are usually symmetric and resolve completely over several days to a week. PLE is usually most severe in the spring or early summer, often diminishing in severity as summer progresses, before disappearing completely during the autumn and winter.1 Many morphologic variants of PLE have been described. The papular form is the most common, followed by the papulovesicular and plaque variants. Other variants, including erythema or pruritus alone (PLE sine eruptione),4 insect biteelike eruption, or erythema multiformeelike eruption, are rare.1 A particular variant in African American patients occurs as ‘‘pinpoint’’ variant.5 The disorder, named ‘‘juvenile spring eruption of the ears,’’ consists of papules and vesicles involving the helices of the ears in boys and young adults during springtime, and it has been considered by several authors as a localized variant of PLE.2,6 Another morphologic variant, a small papular form generally sparing the face and occurring after several days of sun exposure on vacations, has been designated as benign summer light eruption in France.7 The eczematous form probably does not exist, rather representing chronic actinic dermatitis.8 The diagnosis of PLE is usually based on a typical clinical history and characteristic skin manifestations. Histopathologic examination and provocative phototesting can help to establish the definitive diagnosis. There are no diagnostic laboratory tests available for PLE. Laboratory and histopathologic examinations are usually performed to rule out other dermatoses, such as photosensitive LE. Reports of periodic eruptions specifically affecting the elbows are scarce in the dermatologic literature. Recently, Bielsa et al3 reported 7 patients with a pruritic eruption symmetrically affecting both elbows. Five of those patients were previously given a diagnosis of CLE. The eruption consisted of erythematous papules and plaques with a slightly scaly surface specifically located on the elbows, without lesions in other skin areas, which recurred every year during summertime. Histopathology showed combined changes of both LE and interstitial granulomatous dermatitis. No immunohistochemical studies of the infiltrate were performed.3 These authors believed that this peculiar eruption should be included within the spectrum of cutaneous manifestations of LE.

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Table I. Antibodies used in immunohistochemical studies Antibody

Dilution

Specificity

CD2 CD4 CD8 CD30 PD-1

AB75 1F6 C8/144B Ber-H2 PD-1

Clone

1:160 1:50 1:50 1:100 1:10

T cells T-helper cells T-cytotoxic cells Activated T and B cells, Hodgkin cells Immunoregulatory lymphoid cells

CD68 CXCL13

PG-M1 Polyclonal (rabbit)

1:200 1:500

FoxP3 CD79a CD56

236A/E7 JCB117 123C3

1:1000 1:50 1:200

CD123

Il-3 receptor a, 7 7G3

Histiocytes, macrophages Follicular T-helper lymphocytes, angio-immunoblastic T-cell lymphoma T-regulatory cells B cells NK cells, neural cell adhesion molecule Plasmacytoid dendritic cells

1:50

Source

Menarini, Berlin, Germany Menarini, Berlin, Germany DAKO, Hamburg, Germany DAKO, Hamburg, Germany Courtesy Dr Dario Tomasini, Milano, Italy DAKO, Hamburg, Germany Antibodies Online, Atlanta, Ga

Abcam, Cambridge, United Kingdom DAKO, Hamburg, Germany Zytomed Systems, Berlin, Germany BD Biosciences, Pharmingen, San Diego, CA

FoxP3, Forkhead box protein 3; PD-1, programmed death-1; NK, natural killer.

Table II. Spring eruption of elbows: clinical features Case

Sex/age, y

Clinical features/ affected area

Erythematous papulovesicles/ elbows, scattered lesions on upper and lower extremities Erythematous papules/ elbows Erythematous papulesplaques/elbows Erythematous papules/ mainly left elbow

Initial clinical diagnosis

Associations

EM

None

EM

None

Treatment

Evolution/onset

Spontaneous resolution 5 y/Spring-summer in 15 d

1

F/27

2

M/58

3

M/28

4

M/46

5

M/72

Erythematous-edematous plaques/elbows

PLE

6

F/65

PLE

7

F/32

PLE

None

Topical corticosteroids

2 y/Spring

8

F/28

PLE

None

Topical corticosteroids

2 y/Spring

9

M/47

Erythematous papules and plaques with vesicles, bullae, and crusts/elbows Erythematous-edematous papules and plaques/ elbows Erythematous papules/ elbows Erythematous papules/ elbows

Spontaneous resolution 6 y/Spring-summer in 12 d None Spontaneous resolution 4 y/Spring in 16 d Eruption on back 5 y Spontaneous resolution 3 y/Spring-summer before diagnosis of in 14 d Sweet syndrome in another hospital None Topical corticosteroids 5 y/Summer and oral antihistamines None Topical corticosteroids 2 y/Spring-summer

PLE

None

Topical corticosteroids and oral antihistamines

4 y/Summer

EM PLE/LE

EM, Erythema multiforme; F, female; LE, lupus erythematosus; M, male; PLE, polymorphous light eruption.

Sometimes cutaneous lesions of PLE may be very difficult to differentiate from those of CLE. Some authors have suggested that PLE and LE share a

common pathogenesis.9,10 Millard et al9 reported a high prevalence of PLE in patients with LE, and clustering of PLE among first-degree relatives of

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Fig 1. Spring eruption of elbows. A and B, Cases 2 and 3: both elbows were symmetrically affected. C, Case 4: patient was a truck driver and lesions were more severe on left elbow, which was more exposed to sunlight during his work hours. D, Case 6: papulovesicles that grouped into bullous lesions surrounded by intense erythema.

patients with subacute CLE and chronic cutaneous (discoid) lupus erythematosus. Nyberg et al10 studied 337 patients with LE and observed that the prevalence of PLE in this group greatly exceeded the prevalence of PLE in the general population at that geographic latitude. PLE has been described as a presenting symptom in patients with LE and might be thus considered a predisposing factor for LE in some patients with PLE. In addition, several studies have demonstrated in some patients elevated ANA titers in the absence of other apparent LE symptoms.11 In our patients, cutaneous lesions developed a few days after the first sun exposure in spring or early summer, which is more consistent with PLE rather than LE, in which cutaneous lesions occur only 2 weeks after exposure. Furthermore, the immunophenotype of the inflammatory cells present in the cutaneous lesions of PLE and LE seems to be different. PDCs, the natural type-I interferon-producing cells,12 play a pivotal role in the induction of autoimmune diseases and have been found in large number within the cutaneous lesions of some inflammatory diseases, such as psoriasis, contact dermatitis, and LE, but rarely, if at all, in normal-appearing skin.13 Tomasini et al14 investigated the distribution patterns of PDCs in patients with CLE and compared them with other skin diseases showing similar histopathologic

findings. They found conspicuous clusters of PDCs with a perivascular distribution in CLE lesions, but they were absent or found only as single cells scattered throughout the infiltrate or beneath the epidermis in other forms of dermatitis. Furthermore, Wackernagel et al11 investigated immunohistochemically the presence of PDCs in cutaneous lesions of 9 patients with PLE, 11 patients with several variants of CLE, and 7 patients with psoriasis. These authors found that an abundant number of PDCs were present in most specimens obtained from lesions of CLE and psoriasis, but not at all in those obtained from PLE. Therefore, the amount and different PDC arrangement in lesions of CLE represent useful diagnostic tools in the histopathologic differential diagnosis with other forms of dermatitis. Finally, Xie et al15 investigated the features of immunohistochemical characterization of the cellular infiltrate in lesions of CLE and they found an abundant number of CD31, CD41, CD81, CD201, CD251, and CD571 cells within the dermal infiltrate, which indicated a mixture of T and B lymphocytes. In contrast, immunohistochemical studies of the infiltrate in lesions of PLE demonstrated an abundant number of T lymphocytes, with predominant CD41 T-helper cells and some cytotoxic CD81 cells, particularly in late-stage lesions, but B lymphocytes

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Fig 2. Spring eruption of elbows. Histopathologic features of fully developed lesion (case 1). A, Scanning power showing spared epidermis and superficial and deep perivascular infiltrate. B, Dermoepidermal junction showed no anomalies. C, Infiltrate was arranged in dense clusters around vessels of dermis. D, Higher magnification demonstrated that lymphocytes showed small and monomorphous nuclei. (A to D, Hematoxylin-eosin stain; original magnifications: A, 310; B, 340; C, 3200; D, 3400.)

were characteristically absent.16-18 Our patients presented an eruption affecting the elbows showing similar clinical features to those described by Bielsa et al,3 but none of them had a history of LE and histopathologic findings in the cutaneous lesions were more consistent with PLE than with LE, because the lesions showed few or no interface changes and dermal mucin deposits were not seen. In contrast, histopathologic and immunohistochemical features in our cases consisted of edema of the papillary dermis and a perivascular infiltrate, mostly composed of T lymphocytes, whereas B lymphocytes and PDCs were lacking. All these features support a diagnosis of PLE rather than CLE. In conclusion, we believe the summer eruption of the elbows should be considered as a localized form of PLE, rather than a cutaneous manifestation of LE. This is based on its distinct epidemiologic and clinical features, such as the occurrence in spring and summer, the delayed appearance of the lesions several hours or days after exposure to sunlight, and the transient and often recurrent course of the eruption. The histopathology and immunohistochemistry of the summer eruption of the elbows are also consistent with PLE. The striking localization

of the eruption, exquisitely affecting the elbows, remains unexplained. REFERENCES 1. H€ onigsmann H. Polymorphous light eruption. Photodermatol Photoimmunol Photomed 2008;24:155-61. 2. Requena L, Alegre V, Hasson A. Spring eruption of the ears. Int J Dermatol 1990;29:284-6. 3. Bielsa I, Guinovart RM, Fern
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andiz C. Cutaneous lupus erythematosus on the elbows: a peculiar localization. Lupus 2012;21:84-8. 4. Dover JS, Hawk JLM. Polymorphic light eruption sine eruptione. Br J Dermatol 1988;118:73-6. 5. Kerr HA, Lim HL. Photodermatoses in African Americans: a retrospective analysis of 135 patients over a 7-year period. J Am Acad Dermatol 2007;57:638-43. 6. Stratigos AJ, Antoniou C, Papadakis P, Papapostolou A, Sabatziotis D, Tranaka K, et al. Juvenile spring eruption: clinicopathologic features and phototesting results in 4 cases. J Am Acad Dermatol 2004;50:57-60. 7. Hawk J. Benign summer light eruption and polymorphic light eruption: genetic and functional studies suggest that a revised nomenclature is required. J Cosmet Dermatol 2004;3:173-5. 8. Lehmann P, Schwarz T. Photodermatoses: diagnosis and treatment. Dtsch Arztebl Int 2011;108:135-41. 9. Millard TP, Lewis CM, Khamashta MA, Hughes GR, Hawk JL, McGregor JM. Familial clustering of polymorphic light eruption in relatives of patients with lupus erythematosus: evidence of a shared pathogenesis. Br J Dermatol 2001;144:334-8.

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Fig 3. Spring eruption of elbows. Immunohistochemical findings (case 1). A, CD2. B, CD4. C, CD8. D, PD1. E, CD30. F, CD68. G, CD123. H, CXCL13. I, CD79a. (A to I, Immunohistochemical stains, original magnifications: 340.) 10. Nyberg F, Hasan T, Puska P, Stephansson E, H€akkinen M, Ranki A, et al. Occurrence of polymorphous light eruption in lupus erythematosus. Br J Dermatol 1997;136:217-21. 11. Wackernagel A, Massone C, Hoefler G, Steinbauer E, Kerl H, Wolf P. Plasmacytoid dendritic cells are absent in skin lesions of polymorphic light eruption. Photodermatol Photoimmunol Photomed 2007;23:24-8. 12. Jegalian AG, Facchetti F, Jaffe ES. Plasmacytoid dendritic cells: physiologic roles and pathologic states. Adv Anat Pathol 2009; 16:392-404. 13. Wollenberg A, Wagner M, Gunther S, Towarowski A, Tuma E, Moderer M, et al. Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 2002;119:1096-102. 14. Tomasini D, Mentzel T, Hantschke M, Cerri A, Paredes B, R€ utten A, et al. Plasmacytoid dendritic cells: an overview of their presence and distribution in different inflammatory skin

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