Recent Developments in the Diagnosis and Management of Photosensitive Disorders.

Photodermatoses occur in males and females of all races and ages. Onset can be variable in timing and influenced by genetic and environmental factors. Photodermatoses are broadly classified as immunologically mediated, chemical- and drug-induced, photoaggravated, and genetic (defective DNA repair or chromosomal instability) diseases. Advances in the field have led to improved recognition and treatment of many photodermatoses. The purpose of this focused review is to provide an update on the diagnosis and management of a variety of photodermatoses, both common and less common, with review of recent updates in the literature pertaining to their diagnosis and management.

Photo-patch and patch tests in patients with dermatitis over the photo-exposed areas: A study of 101 cases from a tertiary care centre in India.

BACKGROUND: Many patients with dermatitis over photo-exposed body areas are positive to many contact allergens and have a pre-existing allergic contact dermatitis. METHODS: This study included patients who presented to a tertiary centre in India with dermatitis on photo-exposed body areas suspected of chronic actinic dermatitis. Their detailed histories were recorded and cutaneous and systemic examinations were performed. Patch testing was done in all the patients and photo-patch testing was carried out in 86 patients. RESULTS: Altogether 101 patients were included (69 males, 32 females). The most common presentation was lichenified hyperpigmented plaques on the photo-exposed sites. Photosensitivity was recorded in 64 (63%) patients and summer exacerbation in 52 (52%). Exposure to the Parthenium hysterophorus weed was recorded in 70 (69%) patients, 27 (26.7%) had a history of hair dye application and 20 (20%) had a history of atopy. Photo-patch test was positive in 11 (12.8%) patients and patch testing was positive in 71 (70%). Parthenium hysterophorus was the most common allergen implicated and was positive in three (4%) photo-patch and 52 (52%) patch tests. Other positive photo-patch test allergens were perfume mix, balsam of Peru, thiuram mix, Compositae mix and promethazine hydrochloride. Other common patch test allergens were parthenolide, colophony, fragrance mix and p-phenylenediamine (PPD) base. CONCLUSION: In the Indian population parthenium and perfume mix are the most common photoallergens in patients with dermatitis over photo-exposed areas, while parthenium, colophony, fragrance mix and PPD are the common positive allergens.

Llega la primavera y florecen los eritemas polimorfos solares / Spring arrives and with it the polymorphous light eruption

El eritema polimorfo solar es la fotodermatosis más frecuente y suele aparecer en primavera con la primera exposición intensa al sol. Sus manifestaciones cutáneas son variadas y el diagnóstico se basa en la clínica junto al antecedente de exposición solar. En los casos leves, la fotoprotección suele ser suficiente para el control de la enfermedad, pero en formas más graves se requieren otras terapéuticas, como corticoides, antihistamínicos, o fototerapia, que genera una "fotoadaptación" de las áreas de piel afectadas. Presentamos un caso típico de erupción polimorfa solar que respondió de forma adecuada a medidas de fotoprotección. (AU)

The polymorphic solar eruption is the most frequent photodermatosis, and usually appears in spring with the first intense exposure to the sun. It has multiple cutaneous manifestations, and its diagnosis is based on the clinic and the antecedent of solar exposition. In mild cases, photoprotection is usually enough to control the disease, but in more severe forms, other therapies are required, such as corticosteroids, antihistamines, or phototherapy to generate a "photo-adaptation" of the affected skin areas. We present a typical case of polymorphic solar eruption that responded adequately to photoprotection measurements. (AU)

Solar urticaria: Epidemiology and clinical phenotypes in a Spanish series of 224 patients. / Urticaria solar. Epidemiología y fenotipos clínicos en una serie española de 224 pacientes.

BACKGROUND: Solar urticaria is a chronic inducible urticaria also classified as an idiopathic dermatosis. The objective of this paper is to define the phenotypic characteristics of solar urticaria and to evaluate its incidence. MATERIAL AND METHOD: This was a retrospective multicenter study in which data were gathered on the epidemiology and clinical, photobiologic, laboratory, and therapeutic characteristics of solar urticaria. RESULTS: A total of 224 patients (141 women and 83 men) were included from 9 photobiology units. The mean age of the patients was 37.9 years (range, 3-73 years). A history of atopy was detected in 26.7%, and the most common presentation was allergic rhinitis (16.5%). Clinical signs were limited to sun-exposed areas in 75.9% of patients. The light spectrum most commonly implicated was visible light only (31.7%), and in 21% of cases it was only possible to trigger solar urticaria with natural light. The treatments most widely used by photobiology experts were oral antihistamines (65.46%), followed by different forms of phototherapy (34%). Complete resolution was observed most often in patients with solar urticaria triggered exclusively by visible or natural light, with statistically significant differences with respect to other wavelengths (P<.05). No increase in the annual incidence of solar urticaria was observed. CONCLUSIONS: We have presented the largest series of solar urticaria published to date. The epidemiological, clinical, and photobiologic findings confirm previously reported data, although there was a particularly high rate of negative phototests in our series. Reactivity exclusively to visible or natural light was associated with a higher probability of resolution. No increasing trend was observed in the annual incidence.

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.

Prevention of polymorphic light eruption by oral administration of a nutritional supplement containing lycopene, ß-carotene, and Lactobacillus johnsonii: results from a randomized, placebo-controlled, double-blinded study.

BACKGROUND: Polymorphic light eruption (PLE) is the most common photodermatosis. Little is known about the efficacy of systemic photoprotection provided by nutritional supplements in PLE patients. PURPOSE: The purpose of this study was to assess efficacy of nutritional supplement containing lycopene, ß-carotene, and Lactobacillus johnsonii to diminish skin lesions induced by 'photoprovocation' testing in PLE patients. METHODS: In this randomized, placebo-controlled, double-blinded study, 60 PLE patients were supplemented with the nutritional supplement or placebo. For inducing skin lesions, patient skin was exposed to single daily doses of 100 J/cm2 ultraviolet A1 (UVA1) for two consecutive days. Skin lesions were evaluated using a PLE score. Skin biopsies were taken before and after supplementation from unexposed and exposed skin, and intercellular adhesion molecule 1 (ICAM-1) mRNA expression was assessed by real-time polymerase chain reaction. RESULTS: Prior to supplementation, skin lesions were induced in all patients with comparable PLE scores. After 12 weeks, intake of the supplement significantly reduced the PLE score after one exposure as compared with patients taking placebo (P<0.001). After two exposures, these differences were no longer significant. At a molecular level, the development of skin lesions was associated with an increased expression of ICAM-1 mRNA, which was significantly reduced after supplementation (P=0.022), but not with placebo. CONCLUSION: The nutritional supplement provides protection against the development of UVA-induced PLE lesions at clinical and molecular levels.

Photosensitivity in cutaneous lupus erythematosus.

BACKGROUND: Ultraviolet radiation (UVR) is a well-known exacerbating factor for cutaneous lupus erythematosus (CLE), with photosensitivity comprising one of the American College of Rheumatology (ACR) diagnostic criteria for systemic lupus erythematosus (SLE). However, discerning true photosensitivity in this population is difficult due to the broad language utilized by the ACR and the delayed-onset nature of photosensitive lupus lesions. AIMS: The objective of this report is to provide a review of photosensitivity, photoprovocation, and phototherapy in the context of CLE patients. METHODS: A literature review in PubMed was conducted using the terms 'ultraviolet light,' 'lupus erythematosus,' 'photoprovocation,' or 'photosensitivity.' RESULTS: Self-patient reporting of photosensitivity and the broad definition of photosensitivity have led to the wide range of photosensitivity rates in CLE patients. Photoprovocation testing provides a more objective method to measure photosensitivity, but even these trials demonstrate significant differences due to protocol variations. Despite UVR's deleterious effect on lupus patients, ultraviolet A (UVA)-1 may have therapeutic benefits as shown by observations on murine models and human lupus subjects. CONCLUSIONS: Accurately discerning photosensitivity has diagnostic implications for SLE and provides motivation for greater patient adherence to photoprotective methods.

Persistent polymorphous light eruption after ultraviolet A1 phototherapy.

Polymorphous light eruption (PMLE) is the most common photodermatosis and is characterized by the development of a pruritic skin eruption within a few hours to days after sun or artificial light exposure. The eruption usually takes up to two weeks to resolve in the absence of further ultraviolet radiation. PMLE has been reported as a side effect of ultraviolet A1 (UVA1) therapy but characteristics of the eruption, especially the duration until resolution after treatment, has not been described. A 37-year-old female developed an unusually persistent PMLE that lasted for 5 weeks after completion of UVA1 phototherapy.

Phototherapeutic hardening modulates systemic cytokine levels in patients with polymorphic light eruption.

The etiopathogenesis of polymorphic light eruption (PLE) has been linked to impaired UV-immunosuppression, Langerhans cell (LC) retention, and an absence of neutrophil infiltration into UV-exposed PLE skin. We have previously shown that photohardening restores the impaired neutrophil responsiveness to the chemoattractants leucotriene B4 and formyl-methionyl-leucyl-phenylalanin in PLE patients. The aim of this study was to investigate whether photohardening modulates baseline chemokine and cytokine levels which would alter chemoresponsiveness and hence immune function in PLE patients. Sixteen PLE patients received photohardening therapy for 4-9 weeks by 311 nm UVB. Plasma samples were taken both before and within 48 h of the penultimate phototherapeutic exposure. Plasma from these 16 patients, 8 non-irradiated PLE patients, and 14 control subjects was analyzed for IL-1ß, CXCL8 (IL-8), IL-10, IL-17, TNF, CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin), and CCL22 (MDC). These cytokines and chemokines were measured in early spring (March to April) and again in late spring (April to June). PLE patients had a significantly elevated level of CCL11 (p = 0.003) and IL-1ß (p = 0.002) in early spring (before phototherapy). In late spring, after phototherapy, PLE patients had significantly elevated CCL2 (p = 0.002) and TNF (p = 0.002) but a trend for lowered plasma levels of CXCL8 (p = 0.021). When comparing the cytokine shifts from early to late spring, while healthy controls and non-UV-irradiated PLE patients showed an increase, PLE patients undergoing photohardening exhibited a trend for decrease in IL-1ß (p = 0.012). Taken together, our results indicate that photohardening may alter the complex cytokine milieu in PLE, in particular via IL-1ß, helping to normalise the pathophysiologic response to subsequent UV exposure.

Oral administration of a hydrophilic extract of Polypodium leucotomos for the prevention of polymorphic light eruption.

BACKGROUND: Polymorphic light eruption (PLE) is the most common idiopathic photodermatosis. Reactive oxygen species have been implicated in the pathogenesis of PLE. Polypodium leucotomos (PL) is a natural extract from tropical fern leaves with potent antioxidant and anti-inflammatory properties. OBJECTIVE: In this study we sought to evaluate whether a concentrated hydrophilic extract of PL might prevent or delay the photoinduction of typical PLE lesions by artificial ultraviolet (UV) radiation. METHODS: A total of 35 patients with long-standing PLE were included in this open, uncontrolled bicenter study. PLE was induced by photoprovocation with artificial UVB and UVA light, thereafter oral treatment with PL was initiated. Two weeks later a second photoprovocation was performed while the patients were still taking PL. RESULTS: Thirty patients developed PLE lesions after repeated irradiation with UVA. Of these, 18 patients also responded to UVB. After PL treatment, 9 (30%) and 5 (28%) patients, respectively, were unresponsive to repeated UVA and UVB exposure. In the remaining patients, the mean number of UVA and UVB irradiations required to elicit PLE increased significantly from 1.95 to 2.62 (P = .005) and from 2.38 to 2.92 (P = .047), respectively. LIMITATIONS: The study was open and uncontrolled and included a relatively small number of patients. CONCLUSION: Our data indicate that oral PL treatment might be beneficial for the prevention of PLE.

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.

[Chronic actinic dermatitis. Therapy with systemic PUVA and mycophenolate mofetil]. / Chronisch aktinische Dermatitis. Therapie mit systemischer PUVA und Mycophenolatmofetil.

A 66-year-old man was diagnosed with psoriasis in 2001 and treated accordingly; in 2007, the diagnosis was switched to atopic dermatitis and the therapy modified. Initially he improved with fumarates and methotrexate, but then experienced recurrent exacerbations with erythroderma and severe superinfection requiring hospitalization. Based on the modified clinical picture with striking accentuation on the head and back of the hands, we diagnosed chronic actinic dermatitis. In September 2008 immunosuppressive therapy with mycophenolate mophetil (2×500 mg/d) was started. Since the response was modest, photo-hardening with systemic photochemotherapy (PUVA) was added, producing close to complete recovery within 6 months.

Actinic conjunctivitis in children: Clinical features, relation to sun exposure, and proposed staging and treatment.

BACKGROUND: Actinic conjunctivitis is an ocular photosensitivity reaction found mainly in children in certain populations in the Andean regions of South America, Mexico, and in the southwestern United States. Its clinical features, treatment, and possible relation to duration of sun exposure have not been fully described in the ophthalmologic literature. METHODS: A 20-member ophthalmic team traveled to an Andean region of Ecuador to provide ophthalmic care to children. All children with conjunctivitis were examined. A novel 3-stage classification of actinic conjunctivitis, devised by one of the authors, was used to stage the disease. The parents of each child with actinic conjunctivitis were asked how much time the child spent outside. Histopathological evaluations were performed on children who underwent surgery. RESULTS: A total of 206 children were examined, of whom 36 had changes consistent with actinic conjunctivitis. Stage 1 disease was diagnosed in 17 children, stage 2 in 9, and stage 3 in 10 in the most severely affected eye. The amount of time the child spent outside correlated with disease severity (r = 0.77, p < 0.001). Histopathologic samples showed an intense inflammatory response with hyperplasia of the vascular endothelium, pigmentary migration, and occasional eosinophilia. CONCLUSIONS: Actinic conjunctivitis is prevalent among children of the highlands of Ecuador. Although it has an allergic component, our data suggest that the severity of the disease is significantly associated with sun exposure. The finding that the lesions are found only in the exposed conjunctiva supports the hypothesis that UV exposure is the main cause of the disease.

LED photoprevention: reduced MED response following multiple LED exposures.

BACKGROUND AND OBJECTIVES: As photoprotection with traditional sunscreen presents some limitations, the use of non-traditional treatments to increase skin resistance to ultraviolet (UV) induced damage would prove particularly appealing. The purpose of this pilot study was to test the potential of non-thermal pulsed light-emitting diode (LED) treatments (660 nm) prior to UV exposure in the induction of a state of cellular resistance against UV-induced erythema. STUDY DESIGN/MATERIALS AND METHODS: Thirteen healthy subjects and two patients with polymorphous light eruption (PLE) were exposed to 5, 6, or 10 LED treatments (660 nm) on an EXPERIMENTAL anterior thigh region. Individual baseline minimal erythema doses (MED) were then determined. UV radiation was thereafter performed on the LED EXPERIMENTAL and CONTROL anterior thigh areas. Finally, 24 hours post-UV irradiation, LED pre-treated MED responses were compared to the non-treated sites. RESULTS: Reduction of erythema was considered significant when erythema was reduced by >50% on the LED-treated side as opposed to CONTROL side. A significant LED treatment reduction in UV-B induced erythema reaction was observed in at least one occasion in 85% of subjects, including patients suffering from PLE. Moreover, there was evidence of a dose-related pattern in results. Finally, a sun protection factor SPF-15-like effect and a reduction in post-inflammatory hyperpigmentation were observed on the LED pre-treated side. CONCLUSIONS: Results suggest that LED based therapy prior to UV exposure provided significant protection against UV-B induced erythema. The induction of cellular resistance to UV insults may possibly be explained by the induction of a state a natural resistance to the skin via specific cell signaling pathways and without the drawbacks and limitations of traditional sunscreens. These results represent an encouraging step towards expanding the potential applications of LED therapy and could be useful in the treatment of patients with anomalous reactions to sunlight.

Plasma skin resurfacing for regeneration of neck, chest, and hands: investigation of a novel device.

BACKGROUND: Many noninvasive treatments to rejuvenate photodamaged skin are characterized by an unattainable balance between effectiveness and morbidity. The demand for safe, effective procedures has fueled the emergence of plasma skin regeneration (PSR). Preliminary studies have elaborated on the safety and efficacy of PSR for facial skin; however, no evaluation in nonfacial areas has been made. OBJECTIVE: This study was conducted to evaluate the efficacy and safety of PSR in the treatment of moderately photodamaged skin on the neck, chest, and dorsal hands. MATERIALS AND METHODS: Thirty skin areas in 10 patients were selected. Each area received one of three discrete energy settings using a commercially available PSR system. Clinical evaluations of skin texture, pigmentation, wrinkle severity, and side effects were conducted immediately and at 4, 7, 14, 30, and 90 days after treatment. RESULTS: Mean clinical improvements of 57, 48, and 41% were observed in chest, hands, and neck sites, respectively. Significant reduction in wrinkle severity, hyperpigmentation, and increased skin smoothness were achieved. Higher-energy settings yielded greater benefit but also prolonged tissue healing. CONCLUSIONS: PSR offers improvement of moderately photodamaged skin of the neck, chest, and dorsal hands with limited side effects. Further studies are needed to determine the effect of multiple treatment sessions, optimal treatment parameters, and intervals for each site and longevity of clinical results.

Characteristics of diagnosed polymorphous light eruption.

BACKGROUND: The characteristics of polymorphous light eruption (PMLE) have been described in patients evaluated and diagnosed at specialized photodermatology centers. Our goal was to describe the characteristics of PMLE diagnosed in a general clinic setting. METHODS: We used electronic medical records to identify patients diagnosed with PMLE from 2000 to 2002 within a large group practice. We then collected additional information from medical records about patient demographics, lesion morphology, diagnostic testing, and therapies for the selected patients. RESULTS: We identified 142 patients with diagnosed PMLE. After manual chart review, we excluded 18 patients with other forms of photosensitivity, eczema, or collagen vascular disease. Eighty-percent of the remaining 124 patients were diagnosed by a dermatologist during the study period. Females predominated in our patient series and the mean age of PMLE onset was 37.8 years. Lesions were commonly described as papular, edematous papulare, papulo-vesicular, eczematous, and plaque-like. Few skin biopsies were performed, and no patient had phototesting or photopatch testing. Topical corticosteroids and antihistamines were the most commonly prescribed therapies. Only four patients were treated with phototherapy. CONCLUSIONS: Patient demographics and lesion morphology in our cohort were similar to other reports, but patterns of diagnostic testing and treatment were somewhat different than those observed in photodermatology clinics.

Inflammation of actinic keratoses subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase inhibitor.

The Ras-Raf-MEK-ERK signalling pathway is frequently dysregulated in human malignancies, as is angiogenesis and the vascular endothelial growth factor receptor (VEGF/VEGFR) pathway. These kinases are therefore important anticancer targets. The novel, oral treatment sorafenib (BAY 43-9006), has been shown to be an inhibitor of VEGFR, Raf and platelet-derived growth factor in clinical trials against a variety of cancers, with the greatest activity to date observed in metastatic renal cancer. Although side-effects with this targeted therapy are usually not dose-limiting, they frequently involve the skin, and consist of a maculopapular rash, palmar-plantar dysaesthesia, alopecia and xerosis. In this report, we present two patients in whom treatment with sorafenib resulted in inflammation of actinic keratosis, which in some cases progressed to invasive squamous cell carcinoma. This side-effect is of clinical importance, as early recognition is critical for early treatment and may represent a source of additional morbidity to these patients.

Curso clínico de la erupción polimorfa lumínica con medidas de fotoprotección con categoría ULTRA / Evolution of polymorphic light eruption using category ULTRA photoprotective measures

La erupción polimorfa lumínica (EPL) es la fotodermatosis idiopática más común. Suele presentarse en primavera y se caracteriza por la aparición de lesiones pruriginosas de diferente morfología en las zonas expuestas al sol. Aunque existen distintos tratamientos, se considera que la mejor medida consiste en restringir la exposición y utilizar fotoprotectores del factor alto. En este estudio epidemiológico se han evaluado las características clínicas y la revolución de la EPL con medidas de fotoprotección con categoría ULTRA (FPS 90) durante tres meses es una muestra de 26 pacientes. La gravedad de los síntomas y la intensidad de prurito disminuyeron significativamente en tan sólo 15 días hasta niveles irrelevantes y siguió disminuyendo hasta el final del estudio. Los resultados sugieren que la utilización del fotoprotector FPS 90 ayuda a la resolución de las lesiones del brote agudi del EPL.

Photoaggravated pityriasis rubra pilaris.

Pityriasis rubra pilaris (PRP) is a rare papulosquamous condition with an estimated incidence of one in 35,000 to one in 50,000. Psoralen and ultraviolet A (UVA) therapy has been used in its treatment but some patients are reported to be clinically photosensitive. We describe the photoinvestigation of a patient with PRP in whom sensitivity to broadband UVA was demonstrated.

Effectiveness and safety of ALA-IPL in treating actinic keratoses and photodamage.

BACKGROUND: Photorejuvenation involves the use of a light source or laser in reversing the signs of aging. The Intense Pulsed Light (IPL) has demonstrated effectiveness in treating signs of photodamage. Photodynamic therapy is a relatively new and promising treatment for actinic keratoses. OBJECTIVE: To determine the effectiveness of ALA-IPL in treating actinic keratoses as well as reversing the signs of aging. METHODS: A retrospective trial of 17 patients treated with ALA-IPL. Patients were evaluated for improvement of telangiectasias, blotchy pigment, fine wrinkles, coarseness of skin and number of actinic keratoses. All side effects were recorded. RESULTS: 68% of actinic keratoses resolved after one treatment. There was a 55% improvement in telangiectasias, a 48% improvement in pigmentary irregularities and a 25% improvement in coarseness of skin texture. There was minimal change in fine wrinkle appearance. Side effects were minimal including mild erythema and edema for 3-5 days on average. No infections were noted. CONCLUSIONS: ALA-IPL treatment is effective in treating both actinic keratoses and signs of photodamage. In this study, we achieved significant improvement after just one treatment. ALA-IPL is a safe, effective way to treat both actinic keratoses and photodamage with little down time.