Phototests in Japanese patients with papulovesicular light eruption: positive provocation with UVA

In six Japanese patients with papulovesicular light eruption (PVLE), photoprovocative tests were performed by irradiating UVA or UVB on the skin of the back on three consecutive days. One patient developed the typical lesion of PVLE at the test site with two consecutive daily irradiations of UVA. The remaining 5 patients had no abnormal phototest reactions. It was obvious that UVA plays an etiological role in at least some cases of PVLE.     

Contact and photocontact allergy to oxybenzone.

The purpose of this study was to determine the frequency of contact allergy and photocontact allergy to sunscreens. A consecutive series of 54 patients with suspected clinical photosensitivity were assessed. All had the same standardized photobiological investigation from January 1989 to December 1990, including patch tests and photopatch tests with 6 sunscreen agents. Oxybenzone was found to cause 4 cases of allergic contact dermatitis (with photoaggravation in 2), and 3 cases of photocontact dermatitis (13% of patients). This is probably due to the wide distribution of oxybenzone in sunscreens and other cosmetics, 2 patients with polymorphic light eruption and persistent light reactivity, respectively, were regular sunscreen users. Photobiological investigation is necessary to ensure accurate diagnosis, since sunscreen contact or photocontact allergy may simulate other photosensitivity eruptions.     

Polychromatic phototest as a prognostic tool for polymorphic light eruption

BACKGROUND: Diagnosis of polymorphic light eruption (PLE) is based on the patient's history, the morphology of the lesions and the results of phototesting. Skin lesions of PLE can be provoked by repetitive UVB or UVA irradiation. However, about 20% of the patients with PLE have negative phototests. As 24% of the patients with PLE go into remission, it was of interest to search for a link between the results of the phototests and the evolution of the photodermatosis. METHODS: Forty patients with PLE were recruited and repetitive phototests were performed. To ensure a good reproducibility of the phototests, one to three phototests were performed on each patient at different stages of the disease including the period when the PLE had gone into remission. RESULTS: Except for one patient, there was a good reproducibility of the repetitive polychromatic phototests: in each patient, the tests remained positive or negative throughout the disease. After long-term follow-up, two different subgroups were identified: 30 patients with active PLE and 10 patients in remission. There were no clinical differences between these two groups apart from the age of onset and the clinical lesions of the PLE. PLE began at an earlier age in the patients in remission and presented mainly with a plaque-type eruption. In total, 52.5% of the patients had at least one positive polychromatic phototest. Phototests were positive only in patients with active disease. All the patients in remission had negative phototests. CONCLUSIONS: Repetitive phototests could be a prognostic marker for PLE. Two subtypes of PLE were identified on the basis of phototest results: the benign form of PLE with negative phototests, which tends to go into remission, and the more severe and more chronic PLE, with positive phototests.     

Genetic modeling of abnormal photosensitivity in families with polymorphic light eruption and actinic prurigo

Actinic prurigo and polymorphic light eruption are two of the so-called idiopathic photodermatoses, resulting from abnormal cutaneous responses to ultraviolet radiation (photosensitivity). Whereas they are clinically distinct in most cases, there are sufficient similarities between them to suggest they may be related conditions. To take this further, we examined the prevalence of polymorphic light eruption in families ascertained through actinic prurigo probands, as evidence of a shared pathogenesis. We then determined the heritability of photosensitivity in 420 individuals from families ascertained through polymorphic light eruption and actinic prurigo probands using segregation analysis. Across 58 pedigrees the prevalence of photosensitivity in first-degree relatives was 20.9% compared with a population prevalence of 13.6%, giving a relative risk of 1.5 (confidence interval 1.15-2.0) and providing evidence of clustering within families. The prevalence of photosensitivity (predominantly polymorphic light eruption) in relatives of actinic prurigo probands was 23.7%, with a relative risk of 1.74 (confidence interval 1.24-2.36). Modeling for polymorphic light eruption across all pedigrees revealed a strong genetic component with polymorphic light eruption showing a dominant mixed mode of inheritance. The model parameters estimate that 72% of the U.K. population carry a low penetrance polymorphic light eruption susceptibility allele, but that among this highly prevalent genotype only 24% of susceptible females and 13% of susceptible males will have polymorphic light eruption. Expression of polymorphic light eruption in genetically susceptible individuals (intergenotype variance) is determined in large part by a polygenic component, with an important additional environmental component. In summary, this study provides clear evidence that polymorphic light eruption is an inherited condition. It also suggests that polymorphic light eruption and actinic prurigo share a common genetic background, supporting the view that actinic prurigo may represent a human leukocyte antigen-restricted subset of polymorphic light eruption.     

New insights into the mechanisms of polymorphic light eruption: resistance to ultraviolet radiation-induced immune suppression as an aetiological factor

Abstract:  An abnormal immune response has long been thought responsible for the patho-aetiology of polymorphic light eruption, the most common photodermatosis. Recent evidence indicates that polymorphic light eruption patients are resistant to the immune suppressive effects of sunlight, a phenomenon that leads to the formation of skin lesions upon seasonal sun exposure. This immunological abnormality in polymorphic light eruption supports the concept of the biological significance and evolutionary logic of sunlight-induced immune suppression, i.e. the prevention of immune responses to photo-induced neo-antigens in the skin, thereby preventing autoimmunity and skin rashes. This article focuses on the immunological alterations in polymorphic light eruption and the pathogenic significance to the disease state and skin carcinogenesis.     

Photohardening restores the impaired neutrophil responsiveness to chemoattractants leukotriene B4 and formyl-methionyl-leucyl-phenylalanin in patients with polymorphic light eruption

A failure to induce immune suppression after UV exposure has been implicated in the pathogenesis of polymorphic light eruption (PLE). This immunological resistance has been linked to an impaired neutrophil infiltration into the skin following UV exposure. Therapeutic photohardening can restore this abnormal neutrophil infiltration in PLE skin and is thought to be responsible for the prophylactic efficacy. The aim of this study was to elucidate the pathogenic mechanism of the described neutrophil deficiency in PLE. Peripheral blood neutrophil responses to the chemoattractants leukotriene B4 (LTB(4)) and formyl-methionyl-leucyl-phenylalanin (fMLP) were investigated in vitro. Samples from 10 patients with PLE before and after 6 weeks of photohardening therapy were assessed. Flow cytometry was used to measure the changes associated with neutrophil activation. We found a significantly reduced neutrophil responsiveness to LTB(4) and fMLP in PLE patients, which was restored to normal levels after phototherapy. Indeed, PLE neutrophil responsiveness to these two chemoattractants after (but not before) phototherapy was similar to that of age- and sex-matched healthy control subjects. This indicates that an abnormal chemotactic potential to neutrophils is a crucial factor in the pathogenesis of PLE. Normalization following photohardening may therefore account for the therapeutic efficacy by restoring UV-induced neutrophil skin infiltration. Our results reveal a completely novel pathogenic mechanism involved in PLE and offer unique targets for therapy.     

Photodermatoses in Lagos

Light-sensitive dermatoses do not constitute a major problem among the black people in Nigeria. In a 10-year study, only 64 cases (about 0.4% of all dermatologic patients) had light-sensitive dermatoses. Seven of the 10 patients with endogenous photodermatoses were albinos. Two patients with polymorphic light eruption were visiting Caucasians. Only one normally pigmented black Nigerian had xeroderma pigmentosum. Fifty-four patients had photodermatoses from exogenous causes, of which hydroquinone-induced exogenous ochronosis constituted the largest group of patients. Two women had estrogen-induced porphyria cutanea tarda.     

Chronic polymorphic light eruption. Particular wavebands and the effect of carotene therapy.

Forty patients with chronic polymorphic light eruption (CPLE) were tested with the Osram High Pressure Xenon (XBO 150 W) lamp. The tests were performed with unfiltered light, with the Schott WG320 filter for wavelengths above 320 nm and with Schott filters for 310 nm and 361 nm. Abnormal reactions, i.e. lowered MED, papular response or reactions to long wave UV light were observed in almost all patients. A papular response was obtained in more than 50%. With a Schott KG1 filter, which particularly reduces the amount of infrared radiation, there was a great reduction in number of responses. The effect of carotene therapy was evaluated in 17 patients. The therapy had a beneficial effect of low significance only in the case of unfiltered light and not for any particular waveband. Some patients showed clearly an increase in tolerance to sunlight, but this was not related to the plasma level of carotene.     

Provocation testing in polymorphic light eruption using fluorescent ultraviolet (UV) A and UVB lamps

BACKGROUND: Provocation testing is frequently performed during investigation of patients with suspected polymorphic light eruption (PLE). Techniques are not standardized between centres. OBJECTIVES: We sought to evaluate the efficacy of different fluorescent ultraviolet (UV) radiation lamps for provocation testing in PLE. METHODS: We analysed results in 68 patients referred consecutively for phototesting in whom a diagnosis of PLE seemed likely based on clinical history. Patients' case notes were reviewed and responses recorded to provocation testing on forearm skin over three consecutive days using broadband UVA, narrowband and broadband UVB lamps. RESULTS: A positive papular response to broadband UVA exposure was seen in 38 patients [56%, estimated 95% population confidence interval (CI) 43-67.9]. Thirty-four patients (50%) had a positive papular response to narrowband UVB exposure (95% CI 37.6-62.4). The probability of a positive provocation test following irradiation with both lamps was 80.9% (95% CI 69.5-89.4). From April 1999, 34 patients also had provocation testing with broadband UVB. Although six patients (18%) had a positive papular response, they all showed a positive response to one or both of the other lamp types. CONCLUSIONS: Provocation testing with fluorescent UVA and UVB lamps is a cheap and readily available method that can be used as a diagnostic aid to investigate patients with suspected PLE. Using both broadband UVA and narrowband UVB lamps for testing increases the likelihood of confirming the diagnosis than if either lamp is used alone.     

Photoallergic contact dermatitis is uncommon

BACKGROUND: Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare. OBJECTIVES: To analyse the data from 2715 patients who underwent photopatch testing at St John's Institute of Dermatology during the period 1983-98. METHODS: A retrospective analysis of all positive photopatch test episodes was undertaken with the results retrieved from the environmental dermatology database and further verified with the original archived patch test documentation for each individual patient. RESULTS: In 111 patients with positive reactions (4.1%), there were 155 AC or PA reactions to allergens in the photopatch test series. Eighty PA reactions were observed in 62 (2.3%) patients (32 men and 30 women, age range 28-75 years), with UV filters accounting for 52 positive reactions (65%), drugs 16 (20%), musk ambrette 11 (14%) and the antiseptic trichlorocarbanilide one (1%). The most common UV filter photoallergen was benzophenone-3 with 14 positive results, followed by benzophenone-10 (n = 9), isopropyl dibenzoylmethane (n = 6), p-aminobenzoic acid (PABA) (n = 5), octyl dimethyl PABA (n = 5), butyl methoxydibenzoylmethane (n = 4), isoamyl methoxycinnamate (n = 2), ethyl methoxycinnamate (n = 2), octyl methoxycinnamate (n = 2), amyl dimethyl PABA (n = 2) and phenylbenzimidazole sulphonic acid (n = 1). A similar number of AC reactions to UV filters was detected in this study. Thus 49 patients (1.8%) had a total of 75 reactions: 51 due to UV filters and 24 as a result of exposure to fragrances and therapeutic agents. Benzophenone-10 accounted for 13 AC reactions and benzophenone-3 for eight reactions. Twenty-two patients had a PA reaction alone, whereas 19 patients had chronic actinic dermatitis and 15 patients polymorphic light eruption (PLE) in addition. Thus, 34 of the 62 patients (55%) had a preceding underlying photodermatosis. CONCLUSIONS: These results show a low yield of positive photopatch tests. Thus, despite the large increase in the use of UV filters over the last decade, the development of PA reactions remains rare. Furthermore, most of the common UV filter photoallergens identified in this study, including PABA, amyl dimethyl PABA and benzophenone-10, are now rarely used in sunscreen manufacture, while isopropyl dibenzoylmethane was voluntarily removed from the market in 1993. Currently, benzophenone-3 is the commonest contact photoallergen still in widespread use. In contrast, the UVB filter octyl methoxycinnamate, used in a number of sunscreens, produced only two positive PA reactions in 12 years of testing. Nevertheless, although these reactions are extremely rare, patients with photodermatoses such as PLE and chronic actinic dermatitis do represent a group of patients at increased risk of developing photoallergy. Further photopatch test series should be regularly reviewed and updated, as the relevance of individual photoallergens changes over time. Currently, there is no evidence that PA reactions represent a common clinical problem.     

Characterization of photosensitivity in the Smith-Lemli-Opitz syndrome: a new congenital photosensitivity syndrome

Photosensitivity has recently been reported as a feature of the Smith-Lemli-Opitz syndrome (SLO). The aim of this study was to establish the photobiological features of this disorder and to examine the hypothesis that the photosensitivity is caused by the high levels of 7-dehydrocholesterol found in SLO. All known cases of SLO in the U.K. were reviewed and clinical details of photosensitivity were recorded in detail. The action spectrum of the photosensitive eruption was defined by monochromator light testing. Thirteen of the 23 subjects (57%) had severe photosensitivity, and in 10 there was no photosensitivity. No correlation was identified between levels of 7-dehydrocholesterol and severity of photosensitivity, suggesting that the photosensitivity in SLO is not caused by a direct phototoxic effect mediated by 7-dehydrocholesterol. A novel pattern of photosensitivity was observed, with onset of a sunburn-like erythema on sun-exposed skin within minutes of sun exposure, which persisted in most cases for up to 24-48 h before fading. Monochromator light testing in three subjects showed an ultraviolet (UV) A-mediated photosensitivity eruption with greatest photosensitivity at 350 nm. Photosensitivity is a common and prominent feature of SLO and appears to be UVA-mediated. Elucidation of its biochemical basis may provide insight into normal cutaneous protective mechanisms against UVA-induced photodamage, and also sun sensitivity in general.     

Polymorphous light eruption and benign summer light eruption in Italy

Background/purpose: Polymorphous light eruption (PLE) heterogeneity has been postulated, but the existence of benign summer light eruption (BSLE) is controversial. We studied the prevalence of the clinical patterns, criteria distinguishing BSLE from PLE, and diagnostic usefulness of phototest. Methods: Five Italian Photodermatology Centres recruited retrospectively 346 patients with typical clinical history and/or presentation of PLE. Age, gender, skin type, family history and presence of atopy were considered. UVA and UVB MEDs and provocative phototests with UVA and UVB were obtained with a standardized procedure. Photopatch tests were applied according to the IRCDG rules. ANA were assessed by indirect immunofluorescence. Results: Four criteria (predominance of women, shorter latency, uninvolvement of the face and absence of relapse during summer) identified BSLE in only 6.1% of cases. All had positive phototests, mostly with UVA. Uninvolvement of face, short latency and no seasonal relapses identified 11.7% patients, mostly with positive phototests to UVA. Short latency and no seasonal relapses in women identified 11.2% patients. Uninvolvement of face and no seasonal relapses in women identified 8.1% of patients. Uninvolvement of face and short latency in women identified 17.6% of patients. Conclusion: Criteria diagnosed BSLE in only a minority of patients, who were positive at phototesting, mostly with UVA.     

Serum antioxidant capacity in polymorphic light eruption

Polymorphic light eruption is one of the few dermatological diseases in which some antioxidants have been said to be reduced in both the epidermis and the blood. This study measured the hydrosoluble antioxidant capacity in the serum of patients with polymorphic light eruption, using a commercially available kit. All patients were tested in winter, in order to avoid the influence of exposure to ultraviolet light. The results showed that a hydrosoluble antioxidant capacity was significantly decreased (by 29%) in patients with polymorphic light eruption, and b) that females (both patients and controls) has less hydrosoluble antioxidant capacity (by 27%) than males. In addition, the hydrosoluble antioxidant capacity values for females with polymorphic light eruption increased significantly with age, possibly accounting for the well-known propensity of young women to polymorphic light eruption. These last observations have not been reported previously.     

Clinical and biological studies of 26 cases of xeroderma pigmentosum in Northeast District of Japan

Summary Twenty-six patients with xeroderma pigmentosum (XP), who live in the Northeast (Tohoku) District of Japan, were examined for the clinical characteristics of UV-induced DNA synthesis (unscheduled DNA synthesis, UDS) and UV sensitivity of skin fibroblasts or lymphoblastoid cells, or both. A history of consanguineous marriage within two generations was found in 19 of 26 cases (73%). Two pairs of siblings showed similar manifestations and almost the same levels of UDS and of UV sensitivity. Squamous cell carcinoma, basal cell carcinoma, or both were observed on the exposed skin in 14 patients, but no malignant melanoma was found. Cancer had developed in approximately 71% (10/14) of the cancer-bearing patients by the age of 20, and 8 of them belonged to the UDS-deficient group. Neurological manifestations were associated with nine patients, including 3 with typical de Sanctis-Cacchione syndrome (DSC), and most of the cells derived from these patients had a UDS level less than 10% of that of the normal cells. A clear correlation between the levels of UDS and UV sensitivity, on the one hand, and the severity of clinical manifestations on the other could not be detected, but it seems that the UDS-deficient group is generally much more sensitive to UV in terms of cell killing and the induction of sister chromatid exchange (SCE) than the UDS-proficient group. After a photosensitivity test, one patient with mild skin manifestations showed distinct skin tanning without preceding erythema.     

UVB phototherapy and photochemotherapy (PUVA) in the treatment of polymorphic light eruption and solar urticaria

Forty subjects (36 with polymorphic light eruption and four with solar urticaria) were treated during the spring and early summer of the years 1982 to 1985 with either UVB phototherapy (a total of 54 treatment courses in subjects with polymorphic light eruption) or photochemotherapy (PUVA) (18 treatment courses in polymorphic light eruption and eight in solar urticaria patients). Both forms of prophylactic therapy were found to be effective in 90% of those with polymorphic light eruption, and PUVA in all those with solar urticaria. The optimum duration of treatment was 5 weeks. Adverse reactions, although common, were usually slight and rarely required alteration of the treatment regimen.     

Juvenile spring eruption of the ears: a probable variant of polymorphic light eruption

We report 18 cases in which a pruritic, erythematous, papular and vesicular eruption developed on the ears following sun exposure. Four of these patients had, on other occasions, suffered from typical polymorphic light eruption. The clinical features, histological changes, and results of phototesting suggest that juvenile spring eruption of the ears is a localized form of polymorphic light eruption.     

The heritability of polymorphic light eruption

Polymorphic light eruption is classified as an acquired idiopathic photodermatosis, yet it appears to cluster in families, suggesting a possible genetic component. In this study, we assess the heritability of polymorphic light eruption using the classical twin model. Polymorphic light eruption was investigated by a nurse-administered questionnaire in a sample of 420 pairs of adult female twins from St Thomas' Hospital UK Adult Twin Registry, including 119 monozygotic and 301 dizygotic pairs. Probandwise concordance for the presence and absence of disease was calculated and the heritability of polymorphic light eruption assessed by a quantitative genetic model fitting approach using Mx software. The prevalence of polymorphic light eruption was 21% and 18% in monozygotic and dizygotic twins, respectively. A family history of polymorphic light eruption in first-degree relatives (not including the cotwin) was present in 12% of affected twin pairs (where at least one twin had polymorphic light eruption) compared with 4% of unaffected twin pairs, providing evidence of familial clustering (p < 0.0001). The probandwise concordance for polymorphic light eruption was higher in monozygotic (0.72) than in dizygotic twin pairs (0.30), indicating a strong genetic effect. Quantitative genetic modeling found that a model comprising additive genetic (A) and unique environmental (E) factors provided the most parsimonious fit, although a dominant gene effect could also explain our data. In the AE model, 84% (95% confidence interval 65-94%) of the variance in susceptibility to polymorphic light eruption is attributed to additive genetic factors with the remaining 16% (95% confidence interval 6-35%) to unique environmental effects. These data establish a clear genetic influence in the expression of polymorphic light eruption and provide a basis for examining candidate genes that may be pathogenic in this common condition.     

Lupus-like phototriggering in a young woman with benign summer light eruption

We report the case of a young woman with a single history of benign summer light eruption (BSLE) who developed delayed onset annular lupus-like lesions triggered by a polychromatic phototest, 6 weeks after the irradiation. BSLE of French authors is an idiopathic photodermatosis that corresponds to the minor form of polymorphic light eruption (PLE) of Anglo-Saxon authors. This patient may develop a true lupus erythematosus in the future as indicated by this lupus-like phototriggering and in view of the high prevalence of PLE in lupus patients.     

Benign summer light eruption and polymorphic light eruption: genetic and functional studies suggest that a revised nomenclature is required

New research indicates that polymorphic light eruption (PLE) is an autoimmune disease against an ultraviolet radiation-induced cutaneous antigen. PLE may even confer some protection against skin cancer later in life. This new information demands a reassessment of the precise nature and nomenclature of PLE. Benign summer light eruption (BSLE) (lucite estivale bénigne) is the name used in continental Europe, and particularly France, to describe a clinically short-lived, itchy, papular eruption particularly affecting young women after several hours of sunbathing at the beginning of summer or on sunny vacations. Clinically more prolonged forms of solar eruption, starting early in spring and persisting for long periods, have been known in France as polymorphic light eruption (PLE) (lucite polymorphe) ('European PLE'). Investigative studies, however, now suggest that BSLE and some cases of 'European PLE' are part of the same spectrum. In the Anglo-Saxon literature, they are lumped together as PLE ('Anglo-Saxon PLE'). The other cases of 'European PLE', which do not fall within the compass of 'Anglo-Saxon PLE', are, in the Anglo-Saxon literature, classified as either actinic prurigo (AP) (a genetically determined, prolonged, excoriated form of Anglo-Saxon PLE), or chronic actinic dermatitis (CAD) (a sunlight-induced eczema precisely resembling allergic contact dermatitis, apparently to an ultraviolet radiation-induced antigen). It is therefore proposed that: i. the European term BSLE be dropped and that these patients be reclassified within the spectrum of (Anglo-Saxon) PLE, ii. the European use of the term PLE ('European PLE') be discontinued, iii. those previously diagnosed as having 'European PLE' be reclassified as (Anglo-Saxon) PLE, AP or CAD, as appropriate. The benefits of such a change in nomenclature would be twofold, firstly a uniformity of terminology and secondly, and more importantly, terminology would then correlate better with our recently improved understanding of the pathogenesis of these disorders.     

Haemorrhagic polymorphic light eruption: two cases of a rare variant

Polymorphic light eruption is a common photosensitivity disorder of unknown aetiology, that usually presents in the spring or summer months as an intermittent non-scarring, itchy erythematous, papulo-vesicular eruption. We present two cases of haemorrhagic polymorphic light eruption, a rare variant of this condition of which there are no case reports in the literature.