Immunohistopathology of light-induced skin lesions in lupus erythematosus

Recently we have been able to induce pathological skin reactions with UVB, UVA and visible light in patients with lupus erythematosus (LE). The pathological skin reactions had the appearance of spontaneously developed LE lesions. In the present study, using patients with polymorphic light eruption as controls, we subsequently investigated what types of immunohistochemical abnormalities were found in these lesions. It was shown that in the induced skin lesions, phenotypically similar inflammatory cells were found as in spontaneously evolved lesions. Granular deposits of immunoreactants, as found in most spontaneously evolved LE lesions, occurred in 12 out of 16 LE patients 7-10 days after onset of the artificial irradiation. The dermal infiltrates in light-induced LE lesions differed mainly from those in polymorphic light eruption, by the amounts of CD1+ cells (Langerhans' cells). In polymorphic light eruption, the relatively large amount of these cells suggests an active migration of antigen-presenting cells, a mechanism apparently not operative in LE. Our results underline the importance of the pathogenic action of light in LE.     

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.     

Immune sensitization against epidermal antigens in polymorphous light eruption

To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption.     

Polymorphic light eruption limited to areas of vitiligo

Two patients are described with clinical and histological features of polymorphic light eruption (PLE) limited to areas of vitiliginous skin. This phenomenon has not been reported previously and provides evidence for the protective role of melanin in PLE.     

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.     

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.     

Anaphylaxis to 5-methoxypsoralen during photochemotherapy

Photochemotherapy is very effective for the treatment of skin diseases such as psoriasis, as well as for the prophylactic 'hardening' therapy of patients suffering from polymorphic light eruption. The photosensitizers most widely used for oral photochemotherapy are the furocoumarins 8-methoxypsoralen and 5-methoxypsoralen. Beside light-induced phototoxic reactions due to the photosensitizing activity of psoralens, side-effects after the oral intake of psoralens are nausea and vomiting, headaches, anxiety and sleeplessness. We report a rare case of anaphylaxis to 5-methoxypsoralen that developed during prophylactic 'hardening' therapy in a 36-year-old woman suffering from polymorphic light eruption. Anaphylaxis to 5-methoxypsoralen was established by placebo-controlled oral provocation tests.     

Pregnancy Dermatoses

Some aspects regarding the etiology and the nosologic classification of various pregnancy dermatoses are highly controversial. While some authors highlight the existence of premises allowing several skin disorders to be re-grouped within broader disease concepts, others underline the absence of clear, undisputed etiopathogenetic data that could support such classifications. This review exhaustively analyzes the various pregnancy dermatoses (pemphigoid gestationis, intrahepatic cholestasis of pregnancy, impetigo herpetiformis, polymorphic eruption of pregnancy, and the papular dermatoses of pregnancy [prurigo of pregnancy, pruritic folliculitis of pregnancy, and the new classification, atopic eruption of pregnancy]) in an attempt to shed light over this confusing and disputed domain, while subsequently offering an algorithmic approach to their diagnosis and management. While for pemphigus gestationis, intrahepatic cholestasis of pregnancy, and impetigo herpetiformis, specific diagnostic tests such as histopathology, immunofluorescence, or laboratory investigations will confirm the diagnosis, the identification of the other types of pregnancy dermatoses is based only on clinical criteria. In this context, the review argues for the inclusion of the whole group represented by the papular dermatoses of pregnancy within the broad spectrum of polymorphic eruption of pregnancy, separating each of these entities by focusing on their onset: early-onset polymorphic eruption of pregnancy (comprising prurigo of pregnancy, pruritic folliculitis of pregnancy, and atopic eruption of pregnancy) and late-onset polymorphic eruption of pregnancy. In light of the same practical approach guiding it, the review provides updated treatment strategies for each of these conditions.     

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.     

Effect of therapeutic sunscreen cream on phototest reaction in polymorphic light dermatosis

In 15 patients with polymorphic light eruption, we tested the protective action of a therapeutic sunscreen agent containing both UVB and UVA filters. The photoprovocation test showed that the preparation successfully suppressed the development of skin lesions in both wavelengths.     

Erythema multiforme following polymorphic light eruption: a report of two cases

We report two patients in whom episodes of polymorphic light eruption were followed by recurrent erythema multiforme on exposed and nonexposed sites. Treating the polymorphic light eruption with prophylactic PUVA and/or oral prednisolone or cyclosporin prevented the development of erythema multiforme, suggesting that the two events are related. It is possible that erythema multiforme develops as a response to the same causative antigen as polymorphic light eruption.     

Skin testing with simple equipment in photodermatoses

We have reviewed 275 patients who were tested in the light testing clinic in the 10 years from 1972 to 1981. 151 patients (55%) were referred with eczematous changes of the skin attributed to light, while 76 (28%) had a history of polymorphic light eruption. Light tests gave abnormal results in 54(36%) of the dermatitis group, showing a photoallergy in 17 patients and UV sensitivity with or without sensitivity to visible light in 30 patients. 7 out of 10 cases with clinical reactions to phenothiazines also had abnormal test results.
Patients with polymorphic light eruption reacted normally in our test system. Abnormal tests were obtained in solar urticaria, in a few cases of non-eczematous phototoxic reaction, folliculitis of the acne type and systemic lupus crythematosus.
Additional patch tests with standard allergens revealed a high % of contact sensitivity in the 30 UV sensitive patients.     

Photohardening of polymorphic light eruption patients decreases baseline epidermal Langerhans cell density while increasing mast cell numbers in the papillary dermis

The pathogenesis of polymorphic light eruption (PLE) has been linked to a lack of UV‐induced immune suppression. To determine the role of Langerhans cells (LC), mast cells and regulatory T cells, biopsies from PLE patients were taken from exposed sites in spring before and after photohardening with 311 nm or PUVA as well as again in summer. Skin sections were assessed for the presence of Langerin/CD1a+ LC and CD3+, CD4+, CD25+ or FoxP3+ T cells and mast cells. Photohardening transiently decreased the density of epidermal LC and significantly increased a low baseline mast cell density in the papillary dermis of PLE patients. Baseline T cell numbers in the skin were low, and there was no difference in PLE patients among any time point. This suggests that LC suppression together with recruitment of mast cells into photohardened skin may be a key cellular event underlying the mechanism by which phototherapy protects from PLE.     

Polymorphic light eruption sine eruptione

We describe seven patients, four female and three male, who developed intense pruritus on sun-exposed skin without visible change. The clinical features resembled those of polymorphic light eruption (PLE) without rash. Four patients also occasionally developed typical PLE upon sun exposure, but sun-induced pruritus alone occurred most frequently. No patient was taking any drug therapy. One patient developed similar pruritus following solar simulated irradiation, and one following PUVA therapy. All other laboratory investigations were negative. Treatment with low dose UVB phototherapy or PUVA therapy was effective. The condition, which we have called polymorphic light eruption sine eruptione (PLESE), appears to be a variant of PLE not previously reported.     

Polymorphic light eruption occurring solely on an area of naevoid telangiectasia

We report the case of a 60-year-old woman presenting with polymorphic light eruption occurring solely on an area of acquired naevoid telangiectasia. We have hypothesized that increased blood flow in the telangiectatic skin may reduce the threshold for expression of photosensitivity by permitting enhanced inflammatory cell trafficking to the overlying tissue.     

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.     

Polymorphic light eruption and skin cancer prevalence: is one protective against the other?

Background Ultraviolet (UV) radiation (UVR) interacts with chromophores in cutaneous cells with consequent antigenicity. The normal response to this is a downregulation of immune responsiveness. Failure of the immune system to downregulate and to ignore transient photoantigens in human skin results in polymorphic light eruption (PLE), the commonest of the photodermatoses. UVR initiates and promotes skin cancer (SC): UV‐induced immunosuppression permits the expansion of UV‐mutated clones of cells which ultimately lead to SC. Objectives Because there is increased immune surveillance and resistance to immune suppression following UVR exposure in PLE one might expect a protective effect of PLE against SC and, conversely, a reduced risk of PLE among patients with SC. Methods We therefore constructed a prospective case–control study to see if this were the case. Two groups were studied: a group comprising 214 patients with SC and 210 gender‐ and aged‐matched controls, and a group comprising 100 patients with PLE and 155 gender‐ and aged‐matched controls. Each participant answered a questionnaire aimed at establishing personal and family history of SC and photodermatoses. Skin type and exposure to UVR were also documented. Results The prevalence of PLE in people with SC was 7·5%, compared with 21·4% for controls (P < 0·001). The prevalence of SC in patients with PLE was 4% compared with 7·1% for controls. Conclusions Our results show (i) strong evidence of reduced PLE in patients with SC, and (ii) a trend for reduced SC in patients with PLE. The immunological basis of PLE may therefore confer protection against SC.     

Polymorphic light eruption sine eruptione

Seven patients, four female and three male, who develop intense pruritus without visible skin changes in light-exposed areas after sun exposure are reviewed. Onset in all cases has been in childhood or adolescence and the condition has persisted indefinitely except in one patient who has been in remission-for I year and one who was in remission for 5 years before relapse. Itching occurs on sun-exposed areas within 45 min to 24 h and lasts for 1–5 days. No patient has taken photosensitizing medications or suffered from any significant systemic illness. There is a positive family history of polymorphic light eruption (PLE) in one, and of sunlight-induced pruritus in another.
Porphyrin studies and antinuclear factor titres are normal. Cutaneous phototesting of the back by monochromator is normal in the UV-B, UV-A and visible light ranges. Irradiation from a xenon arc solar simulator in one patient induced intense pruritus with no visible skin changes on the tested sites of the anterior forearm and back in a time course mimicking that of sun-induced symptoms.
Treatment by sun avoidance, topical sunscreens and antihistamines has been only partially effective.
Two patients have subsequently developed occasional typical PLE upon sun exposure, but sun-induced pruritus alone occurs most frequently. This suggests that polymorphic light eruption sine eruptione is a variant of PLE and, to our knowledge, is the first report of this condition.     

Photoallergic contact eczema caused by 4-isopropyldibenzoylmethane

Dibenzoylmethanes are widely used in UVA absorbing sunscreens but also in cosmetics protecting against skin aging. We report on a 25 years old female with photoallergic contact dermatitis caused by 4-Isopropyl-dibenzoylmethane (Eusolex 8020, Merck), who had taken Contralum Ultra Creme because of a polymorphic light eruption.