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Polymorphous Light Eruption

Erhard Holzle, M.D., Gerd Plewig, M.D., Renate von Kries, M.D., Percy Lehmann, M.D. Department of Dermatology, University of Diisseldorf, Diisseldorf, F. R. G.

Polymorphous light eruption (PLE) is a common photo­ cells, and spongiosis in the lower epidermis. The most dermatosis of unknown etiology. It affiicts mainly fair­ important differential diagnoses are solar urticaria, pho­ skinned patients, with a preponderance of young females. tosensitive erythema multiforme, and lupus erythemato­ There is, however, no absolute restriction as to age, sex, sus. or race. The action spectrum of PLE is under debate. Repro­ Clinical variants include the papular, vesiculo-bullous, duction of skin lesions has been reported with UVB, UV A, and hemorrhagic variety, as well as plaque, erythema mul­ and, rarely, visible light, with UVA probably being the tiforme-like, and insect bite (strophulus)-like types. Skin most effective part of the spectrum. lesions appear only in certain exposed areas hours or a few More important than treatment of PLE is prophylaxis. days after intense sunshine, and are nearly always mono­ UV A- and UVB-effective sunscreens are of some help. morphous in the same patient. The rash subsides sponta­ Phototherapy and especially photochemotherapy (psoralen neously within several days without leaving scars. + UVA; PUV A) offer effective ways to decrease light The histopathologic picture is characteristic and shows sensitivity. Systemic treatment with chloroquine or f3-car­ a perivascular lymphocytic inftltrate in the upper and mid­ otene has been disappointing. ] Invest Dermatol 88:325-385, dle corium with subepidermal edema, vacuolization of basal 1987

t was recognized in the early 19th century that certain ecze­ several morphologic variants. Our experience is based on obser­ matous reactions were caused by sunlight. Willan [1] was vations in more than 250 patients in the years from 1977 to 1985 the first to use the term "eczema solare." In 1879 Sir Jonathan [8-11). Hutchinson [2] presented 14 patients under the diagnosis I CLINICAL FEATURES "summer prurigo. " There is reason to believe that "prurigo aestivalis," "prurigo adolescentium," and "acne prurigo" syn­ Polymorphous light eruption is a very common photodermatosis, onymously designated similar sun-induced skin disorders. Rasch, but the true prevalence among the population is not known. In in 1900 [3], simplified the terminology by introducing the term a survey of 271 apparently healthy subjects, 10% gave a history "polymorphous light eruption (PLE). " This designation was widely consistent with PLE [12]. Many persons are aware of a transient accepted to characterize urticarial, papular, vesicular, and ecze­ "sun allergy" but never visit a dermatologist because they know matous reactions precipitated by light [4]; however, it did not how to manage the problem by themselves. Individual suscep­ clarify the nosology of photodermatoses. tibility varies greatly, and only the most severely afflicted patients A variety of sunlight-evoked eruptions, such as solar urticaria, are seen by physicians. In many patients, PLE appears during the hydroa vacciniforme, porphyrias, photoallergic dermatitis, pho­ first days of vacationing on the beach or in high altitudes. When tosensitive erythema multiforme, and lupus erythematosus (LE) the patient returns home the eruption has resolved spontaneously fell under this diagnosis. It was only during the past decades that and the pliysician who is asked for help can only conceive a these differential diagnoses have been separated and polymor­ diagnosis by the patient's history. phous light eruption has been defmed as a clinical entity [5-8). Polymorphous light eruption seems to occur most frequently Until now, however, it remains difficult, if not impossible, to among fair-skinned populations. Large series are reported from distinguish in certain patients between polymorphous light erup­ Scandinavian countries [13,14], but the eruption is not confmed tion and light-induced subacute or discoid cutaneous lupus ery­ to a certain race or skin color [7]. It has been reported in Blacks, thematosus, or photosensitive erythema multiforme. Orientals, and in Native North and Latin Americans [15,16]. This review describes the growing knowledge about PLE. We Among the latter, the familial occurrence is a characteristic fea­ put forward our concept of the disease as a distinct entity with ture. This peculiar photodermatosis might represent an entity different from PLE observed in whites [17]. Inheritance in an autosomal-dominant mode with a reduced penetrance has been Reprint requests to: Prof. Dr. E. Holzle, Universitatshautklinik, Moor­ reported in 56% of patients evaluated in Finland [18] and in 75% enstr. 5, D-4000 Diisseldorf 1, F.R.G. of Canadian Inuit patients [19]. In other series, genetic predis­ Abbreviations: position ranged from 3-45%. Jansen [18] suggested that patients DLE: discoid lupus erythematosus in other reports might not have been questioned as thoroughly LE: lupus erythematosus and, therefore, genetic predisposition in general might be under­ MED: minimal erythemal dose PLE: polymorphous light eruption estimated. PUV A: photochemotherapy (psoralen + UV A) There is agreement that the time of onset is most commonly SCLE: subacute cutaneous lupus erythematosus during the early adult life [7,13], but the eruption may also start UVA: ultraviolet A in childhood. In children the face and ears frequently are involved. UVB: ultraviolet B Similar cases have been described under the designation ''juvenile

0022-202X/87/S03.50 Copyright © 1987 by The Society for Investigative Dermatology, Inc.

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spring eruption" [20,21], which is probably part of the PLE spec­ borne contact dermatitis. Prurigo associated with sun exposure trum. Actinic prurigo [22,23], however, is in our view a separate might by seen in actinic prurigo, which represents an entity sep­ disorder that bears resemblance to the hereditary variant of PLE arate from PLE. The reason we do not observe eczematous lesions among North, Central, and South American Natives (18,24]. in our patients might be the lack of chronic exposure to high­ Features that distinguish these disorders from PLE are involve­ intensity solar radiation. In the F. R. G. the summer season is ment of non-sun-exposed areas, lack of complete clearing during short and longer periods of sunny weather conditions are rare. the winter season, and presence of chronic eczematous lesions. In our patients [8,11] the papular type, along with the hem­ In our experience, 90% of PLE patients are women. This is in orrhagic and insect bite (strophulus)-like varieties, the plaque accordance with the findings of Clorius and Jung [6] and Jansen type, the vesiculobullous type, and an erythema multiforme-like [13]. Others have found a preponderance of men [25,26] or an type make up the spectrum of PLE. We do not share the opinion equal sex distribution [27,28]. The reason that, in some studies, that the clinical picture might be polymorphous in the same in­ women are more commonly afflicted is not well understood. It dividual [5,6] or that combination or transition between the var­ is possible diat the preponderance of females does not reflect the ious types might occur [7]. In our series skin lesions were mon­ true prevalence, which might be equal, but rather might reflect omorphous in any one patient. a higher rate of reporting of the rash by women. Papular Type It is the most common type of PLE. Small Lesions of PLE are confined to sun-exposed body sites. In papules or papulovesicles are disseminated or densely aggregated contrast to others [5,7,13] we have neither observed lesions on on a patchy erythema (Figs lA,2A). areas covered by clothing nor a tendency of the eruption to gen­ eralize. In our experience, PLE is confined to certain sites of Hemorrhagic Type Rarely, the papular lesions are hemor­ predilection even when large areas are sun-exposed. In order of rhagic. decreasing frequency of involvement, these sites are: V-neck, Insect bite (Strophulus)-like Type This is a peculiar, rare dorsal forearm and back of hands, upper arms, face, shoulders, variety of the papular type. The lesions are few, scattered, and thighs,and lower legs. Variations among different patients occur. consist of small urticarial papules topped by a tiny vesicle. In exquisitely sensitive individuals larger parts of the trunk are involved, too. Jansen [13] notes that lips and eyes are frequently Plaque Type This is the second most common variety in our involved, and reports that patients experience general symptoms, patients. It occurs frequently on the face [7] and resembles sub­ like chills, headache, fever, and nausea after sun exposure. acute cutaneous lupus erythematosus (SCLE), with its sharply The reaction is of a delayed type. Lesions appear from several demarcated, erythematous, elevated, often urticarial plaques. hours to a few days after intense sun exposure. A characteristic Erythema Multiforme-like Type It shows typical target le­ sequence of events is reported by most patients, and the dynamics sions and occurs less frequently. ofthe lesions can be observed when PLE is experimentally evoked by phototesting. Itching occurs first; it is followed by patchy Vesiculobullous Type It consists of tense vesicles and small erythema. Finally, distinct lesions emerge, which may coalesce. bullae on an erythematous base. It seems to be frequent among Thesequence from itchy, patchy erythema to sparsely distributed North American women vacationing to Hawaii [34]. In Europe andthen densely aggregated skinlesions requires increasing amounts it is very rarely observed [35]. ofradiation energy. Lesions are present for hours or several days HISTOPATHOLOGY AN D and resolve spontaneously without residues when further sun IMMUNOHISTOPATHOLOGY exposure is avoided. Scaling, hyperkeratosis, lichenification, or scarring are not primary lesions in PLE. These changes may occur In 1960 Wright and Winer [36] gave a description of the histo­ secondarily due to rubbing or scratching and prolonged sun ex­ pathologic pattern seen in PLE that has gained wide acceptance. posure. Also the clinical picture might be altered by a concomitant They found parakeratosis, subepidermal edema, vascular dilata­ sunburn reaction. The majority of patients experience seasonal tion, and lymphocytic infiltration. Sometimes acanthosis, liq­ recurrences over many years, with decreasing sensitivity after uefaction degeneration of the basal layer, and diminished elastic repeated sun exposures. Finally, the problem may resolve spon­ fibers were observed. McGrae and Perry [5] stressed the similar­ taneously after many years [13,29]. ities to lymphocytic infiltration Jessner. Lamb et al [26], as well Many patients experience the elicitation of skin lesions by sun­ as Lever and Schaumburg-Lever [37] distinguished the plaque light through window glass, e.g., in airplanes, cars, and trains. type of PLE from LE by absence of vacuolar alteration of basal This was already observed by early authors [25] and indicates cells, a view that did not hold true [7,8,38]. The main features that the action spectrum is not confined to sunburn radiation. characteristic for PLE are observed in the common papular type [7,8]. In other morphologic variants, this basic pattern is also MORPHOLOGIC VARIANTS prominent, but certain features might be pronounced or addi­ Most authors agree that there are different morphologic variants, tional features superimposed. with the papular variety being the dominant type [13,28,30]. The pattern of PLE, seen in the papular type, shows a superficial Lamb et al [31] and Epstein [32,33] in their series distinguished and deep perivascular lymphocytic infiltrate with an interstitial plaque, prurigo-like, and erythema multiforme-like types from component in the upper dermis. There are subepidermal edema the papular, eczematous, and erythematous variety. The latter and vacuolization of basal cells, exocytosis of lymphocytes, and was designated erythema solare perstans. In his review [7] Epstein focal spongiosis. Sunburn cells are notably absent or sparse (Figs refers to small papules, large papules that may coalesce and form lB,2B). plaques, papulovesicular lesions, erythema multiforme-like le­ In the plaque type the infiltrate tends to be lichenoid, subepi­ sions, prurigo-like nodules, and an eczematous response that may dermal edema is pronounced, and spongiosis is widespread, in­ become secondarily lichenified by rubbing and scratching. Re­ volving the lower epidermis. cently, a vesiculobullous variant of PLE was described [34,35]. The erythema multiforme-like type exhibits a prominent su­ In our view, diffuse erythematous response, eczematous re­ bepidermal edema sometimes forming a blister, and few extra­ actions, and prurigo-like nodules are not part of the PLE spec­ vasated erythrocytes. Epidermal necrosis may or may not be trum.These lesions characterize separate light-induced disorders, present. which comprise differential diagnoses of PLE. Widespread diffuse In the vesiculobullous type spongiotic vesicles and subepider­ erythema following sun exposure might occur in systemic LE or mal blisters are formed. in the presence of a phototoxic photosensitizer. Eczema in ex­ The insect bite (strophulus)-like type shows focal necrosis in posed areas is a feature of photoallergy, photosensitive eczema, the upper malpighian layer, and in the hemorrhagic type there is persistent light reaction, light-aggravated atopic eczema, or air- notable extravasation of erythrocytes. Figure 1. PLE, papular type, genuine lesions. A, Papules scat­ tered on chest 48 h after sun exposure; B, Histopathology from another patient with similar lesions shows perivascular and in­ terstitial lymphocytic infiltrate in the upper corium with subep­ idermal edema, vacuolization of basal cells, and spongiosis.

Figure 2. PLE, papular type, experimentally induced lesions. A, Urticarial papules that coalesce emerged in the moderately pigmented test area on the upper arm 24 h after irradiation with A toO J/cm2 UVA (UVASUN 3000); B, Superficial and deep per­ ivascular lymphocytic infiltrate with subepidermal edema, vac­ uolization of basal cells, and spongiosis.

B

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Neutrophils and eosinophils are only present in a few cases [7]. evoked by sun exposure through window glass while patients are We have noted them only in the vesiculobullous type. This is, riding on trains, airplanes, or in cars. Furthermore, sunburn is however, inconsistent with other reports [34]. not a prominent feature in PLE, neither clinically nor micro­ Using monoclonal antibodies to defme subsets of infiltrating scopically. mononuclear cells in papular PLE, Muhlbauer et al [39] found The question as to whether erythemal or pigmentary responses that the perivascular infiltrate was predominandy composed of to solar radiation may differ from normal reactions in patients T cells with a slight but inconsistent preponderance of cyto­ with PLE has stimulated research that produced confticting. ex­ toxic/suppressor cells over helper/inducer cells. Macrophages perimental data. Thune [14] as well as others[54] found the MED represented less than 5% of the infiltrating cells. Langer­ of sunburn radiation lowered in patients with PLE. In contrast, hans/indeterminate cells were found to be increased in number. Jansen [55] reported normal values, perhaps with a slighdy de­ The same group [40] studied PLE by direct immunofluores­ layed fading of the erythema; pigmentary responses were also cence technique and detected intervascular and focal perivascular found to be normal. deposition·of fibrin. In some patients, C3 and IgM was found in We could not discern any differences in MED-UVB or pig­ the walls of venules. The lupus band test was negative in all mentary reactions induced by UVA between patients with PLE subjects. Recendy, Moncada et al [41] found a predominance of and normal controls [9]. Others, too, have questioned the use­ T helper cells and Ia + cells in the dermal infiltrate of PLE. fulness of MED-UVB as a diagnostic parameter [7]. ACTION SP ECTRUM DIFFERENTIAL DIAGNOSIS The action spectrum ofPLE is not known. There have been many The diagnosis of PLE is based on a patient's histo.ry and clinical debates about the wavelength and energy requirements for elic­ features of lesions. The time course of PLE, with its onset hours iting skin lesions. Experimental results are conflicting and some­ after intense sun exposure and spontaneous fading (without res­ times contradictory. Factors that may relate to the reported var­ idue) of lesions within hours or days is very characteristic. It aids iability include differences in individual susceptibility, seasonal in establishing the diagnosis when the patient presents without variations, differences in test sites, light sources, and interpreta­ skin lesions. A diagnosis can be made almost with certainty when tionof test results, as well as the clinical variety ofPLE, including the patient presents with a typical rash or whenPLE is reproduced geographic differences. Many investigators report the induction by phototesting in the laboratory. Biopsies of genuine or exper­ of skin lesions with sunburn radiation between 280 and 320 om imentally induced lesions may confirm the diagnosis, if other [32,33,42,43,44]. Most of these authors used radiation from high­ differential diagnoses cannot be excluded clinically. Staining with pressure mercury or xenon lamps or carbon arc sources with hematoxylin and eosin suffices; special stains are of little help, appropriate filters. In some instances responses to UVC were perhaps with the exception of direct immunofluorescence tech­ noted [33]. nique, if lupus erythematosus is suspected. On the other hand, Langhof and Sprossig [45], Wiskemann It is our belief that chronic skin lesions with pronounced epi­ andWulf[46], and Gschnait et al [47] were able to reproduce skin dermal changes are not part of the PLE spectrum. Thus, light­ lesions ofPLE with long-wave UV light (UVA). In a multitude induced disorders showing eczematous lesions, e. g., photoallergic of experimental studies, various authors came to the conclusion dermatitis, photosensitive eczema, and persistent light reaction that the action spectrum might range from UVB, to UVA, and are excluded from PLE by their morphology. into visible light [14,27,44,48-51]. In some instances, an additive Solar urticaria may mimic the plaque type ofPLE. Time course effect of infrared radiation was observed [13,14]. of whealing and the reproduction of typical hives using low doses During the years from 1977 to 1985 we tried to induce skin of electromagnetic radiation are characteristic for solar urticaria. lesions experimentally in more than 250 patients. Until 1982, 180 Photosensitive erythema multiforme is a rare condition [56]. It patientswere tested by using various procedures [8]. Monochro­ is difficultto separate this disorder from the erythema multiforme matic light, both UV A and UVB, as well as polychromatic UVA type ofPLE. Clinical and histologic pictures are very similar[57]. in doses up to 40 J/ cm2 failed to elicit PLE. When UVA from a The following features may help to differentiate light-sensitive high-intensity apparatus (UVASUN 3000; Mutzhas, Munich, FRG) erythema multiforme fromPLE: (1) The former occurs 1-14 days [52] was given in doses of 60-100 J/cm2, up to 90% of patients after sun exposure. (2) Immune complexes may be detected in developed lesions ofPLE if stringent requirements were met (Ta­ the initial stage, and the lymphohistiocytic infiltrateis perivascular ble I). Adhering to the same experimental procedure but using and interstitial in the upper corium. (3) Sometimes eosinophils polychromatic UVB in minimal erythemal doses (MED) up to and extravasated erythrocytes are prominent, and the epidermis 4, we were unable to reproducePLE at that time; however, only shows focal necrosis. a few patients were tested. The deposition of immune complexes in venules of the skin Recendy, we have extended our experience to another 90 pa­ triggered by UV erythema has been discussed as the underlying tients. These were tested with UV A and UVB (UV 800 equipped pathogenetic mechanism in photosensitive erythema multiforme with fluorescent bulbs, Philips TL 12; Waldmann, Villingen­ [58]. Schwenningen, FRG) on a contralateral or adjacent skin site, fol­ Lupus erythematosus is the most important differential diag­ lowing the method described (Table I). About 60% of patients nosis, clinically and histologically. Subacute cutaneous lupus er­ showed lesions ofPLE; out of this group 75% revealed sensitivity ythematosus and the tumid type of discoid LE (DLE) may present to UVA, 10% to UVB, and 15% reacted to both UV A and UVB with lesions very similar to the plaque type ofPLE. In LE, how­ [11]. The smaller yield of positive reactions compared with the ever, waxing and waning of lesions are not as closely correlated previous study [8] might be due to the fact that some patients to sun exposure as in PLE. Lesions usually persist for several were tested in summer or fall, at a time when their skin was less weeks or months even without further UV exposure. When LE UV sensitive due to hardening. lesions are induced by experimental UV irradiation [59] it takes Similar results were found by Ortel et al [53], who were able at least several days, in most cases 1-2 weeks or longer, for lesions to reproduce skin lesions in 50% of 142 patients. In 56% the to appear. This prolonged time course differs from PLE. eliciting wavelengths were found in the UVA range, in 17% in Histologically, the lymphocytic infiltrate in LE frequendy ex­ the UVB spectrum, and in 26% in both. tends perivascularly and around the adnexa in the deeper corium. In view of these data it appears that, in the majority of PLE There might be mucin deposition between collagen bundles[60]. patients, long-wave UV is most effective in eliciting skin lesions. Subepidermal edema is not pronounced, and liquefaction degen­ A small subgroup of patients shows additional sensitivity to UVB eration, if present, is confined to the epidermal basal cell layer. or may react to UVB exclusively. These findings are in accord­ Spongiosis is absent. Sometimes neutrophils are seen in vessels ance with the observation that eruptions of PLE are frequendy of the superficial plexus. In most cases of PLE the perivascular 36$ HOLZLE ET AL THE JOURNAL OF INVESTIGATIVE DERMATOLOGY

Table I. Recommendations for Provocative Photo testing tive effect. Patients with PLE frequently show "hardening" with in PLE decreasing UV sensitivity during spring or early summer. It seems worthwhile to induce this protective mechanism by controlled Test time Before the PLE season starts exposures to sunlight [77] or artificial UV sources [78-80]. Also, Test site Previously involved body areas. Avoid pigmented skin PUVA treatment was used to prevent further attacks of PLE Size of test area No less than 5 x 10 cm [47,81-84], and was found to be superior to phototherapy Light source Use polychromatic UV in large doses [53,62,83,85]. Until more is known about the long-term hazards UV dose UVA: 60-100J/ cm2 of PUVA therapy, patients should be monitored carefully, al­ UVB: 2MED though the number of exposures and the cumulative UVA doses Repeat irradiations on day 2 and 3, if necessary are quite small. We do not advocate PUVA therapy in PLE as the treatment of first choice, but inform our patients about the benign nature of PLE and recommend sun-protective measures lymphocytic infiltrate reaches only into the mid-dermis. Subep­ in combination with skin "hardening" using natural sunlight. If idermal edema is a prominent feature. Vacuolization accompanied this fails, phototherapy is used. Only those patients who are by spongiosis occurs in the 2 or 3 suprabasal cell layers. Intra­ exquisitely sensitive to UV are treated with PUVA therapy in cellular and intercellular edema of the lower part of the epidermis, our department. The mechanism by which phototherapy or pho­ in combination with subepidermal edema, gives the dermoepi­ tochemotherapy induce protection is not completely understood. dermal interface a spongy appearance. The histopathologic dif­ Besides increased melanization and thickening of epidermis and ferences mentioned are prominent only in fully developed lesions. stratum corneum, factors that enhance UV absorption in the ep­ In the initial stage ofLE or PLE it is extremely difficult,sometimes idermis and provide a protecting shield for the underlying dermis, impossible, to distinguish between the two diseases on histo­ immunologic mechanisms cannot be excluded. pathologic grounds. Direct and indirect immunofluorescence are HYPOTHESES ON ETIOLOGY AND PATHOGENESIS of limited value because they may yield negative results in early OF PLE stages of LE or may be found positive in some patients with PLE who, however, do not meet other criteria of LE [29]. It is our Apart from the fact that PLE is induced by electromagnetic ra­ impression that there might be a subgroup of patients that cannot diation emanating from the sun, nothing is known about its etiol­ be separated clearly either from DL E, SCLE, or PLE. It is con­ ogy, despite many investigative studies. ceivable that these patients eventually progress into LE. This view In their search for an endogenous photosensitizer, European is, however, not substantiated by follow-up studies [29,30], in authors focused on gastrointestinal abnormalities in PLE patients which PLE patients were not found to develop LE. [45,86]. Also urinary excretion of an indole derivative, called "Kimmig's light band" [87] was described but was not found to THERAPY AND PROPHYLAXIS be specific for PLE [88]. Others [73,74] put forward the hypoth­ Some patients may experience a cooling and beneficial subjective esis that disturbances in the tryptophan metabolism might be the effect by local application of zinc lotion in acute-stage PLE. Top­ cause of photosensitization. None of these theories account for ical or systemic steroids may ameliorate inflammation or itching the pathomechanism of PLE. and shorten the eruption. In few patients eruptions of PLE can Many investigators hold the view that PLE is related to a cell­ be suppressed by prophylactic systemic steroid treatment. Con­ mediated immunologic reaction [7]. The time course of the re­ trolled trials are lacking and it seems inappropriate to treat this action, with a delay after the initiating sun exposure, the clinical chronic, intermittent, self-limited, and benign disease with sys­ picture, and histopathologic findings bear similarities to the ecze­ temic steroids. More important than therapy of the acute eruption matous reaction of delayed-type hypersensitivity. A relevant pho­ seems the prevention of further attacks by prophylactic measures. to allergen has not been identified. Functional disturbances of lym­ Light protection, phototherapy, photochemotherapy and, to some phocytes have been found only inconsistently. Horkay and Meszaros extent, systemic drugs offer ways to decrease UV sensitivity. [89] described UV-induced lymphocyte transformation in PLE. Sun protection by protective clothing or staying in the shade Also, a defect in the excision repair mechanism in lymphocytes may prevent PLE. The usefulness of topical sunscreens is limited, of PLE patients was reported [90], but was not confirmed by although sun blockers have been found effectivein UVB-sensitive others [91,92]. patients [62], and broad-band screens (UVB plus UVA) or phys­ In recent studies on cell-mediated immunity in PLE, a transient ical sunscreens may be beneficial in other patients [8,51,63,64]. decrease [93] as well as an increase[41] in number of lymphocytes Systemic treatment with J3-carotene yielded different results. was found; no inhibition of leukocyte migration was detected Some authors found only modest improvement of UV tolerance [94]. The number of peripheral T cells and response of peripheral not sufficient to enable the patient to perform normal outdoor lymphocytes to phytohemagglutinin, concanavalin A, and pu­ activities [65,66], while others report complete remission [14,67] rified protein derivative of tuberculin was found normal before (uncontrolled studies). J3-Carotene was also used in combination and after PUVA treatment [95]. This argues against the distur­ with canthaxanthin [68], a combination recently banned by the bance in lymphocyte function as a cause of PLE. German Federal Department of Health. In controlled trials[69,70] J3-carotene was ineffective in many cases. The same holds true REFERENCES for chloroquine [68], although antimalarials, mainly chloroquine 1. Bateman T: A Practical Synopsis of Cutaneous Diseases According and quinacrine, have been commonly used to treat PLE [61,71,72]. to the Arrangement of Dr. Willan. Philadelphia, Collins & Croft, Results have been unimpressive. 1817, pp 251-253 Some authors [73,74] assume that the underlying mechanism 2. Hutchinson J: Lectures on Clinical Surgery: On Certain Rare Dis­ in PLE is a disturbance in the tryptophan metabolism, with ac­ eases of the Skin. Volt. London, Churchill, 1879 cumulation of kynurenic acid, which may act as a photosensitizer. 3. 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