Phototherapy in the Evaluation and Management of Photodermatoses.

Ultraviolet light (UV) and visible light are important components in the diagnosis of photodermatoses, and UV has the unique ability to also be used to manage photodermatoses. Phototesting, provocative light testing, and photopatch testing can provide important information in diagnosing patients with photodermatoses; phototesting can be used to determine the starting dose for phototherapy in these patients. Once photosensitivity is established, narrowband UVB and UVA1 therapy have helped to improve the quality of life of photosensitive patients, such as those with polymorphous light eruption, chronic actinic dermatitis, and solar urticaria.

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.

Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients.

Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.

Sobre el uso de la fototerapia en el manejo de las fotodermatosis / On the Use of Phototherapy in the Management of Photodermatoses

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Successful Short Desensitization Treatment Protocol with Narrowband UVB Phototherapy (TL-01) in Polymorphic Light Eruption / Protocolo de desensibilización corto y eficaz con NB-UVB (TL-01) en la Erupción Polimorfo Lumínica

Introduction: Polymorphic light eruption (PLE) is a common idiopathic photodermatosis that typically presents with pruritic papular or papulovesicular lesions on sun-exposed skin between spring and autumn. In many subjects PLE is mild, and can usually be prevented by the use of broad-spectrum topical sunscreens and a gradual increase in sunlight exposure. However, in some individuals, sunlight exposure results in florid PLE and they often benefit from prophylactic desensitization treatment using phototherapy in early spring, an artificial method that induces a "hardening" phenomenon. Objective: To describe and evaluate the efficacy of a short desensitization protocol, based on a one-month-treatment, administered twice a week with narrow band UVB in subjects with severe polymorphic light eruption (PLE). Methods: A retrospective, open planned and non-randomized study to assess the efficacy of UVB phototherapy in prevention of polymorphic light eruption. Results: Fifteen subjects diagnosed with severe PLE were treated with the standard protocol in our Photobiology Unit between 2014 and 2015. The effect of hardening was sustained during follow up in 87.5% of desensitization treatments. A statistically significant association (p<0.05) between the years of duration of the PLE and the response to treatment was found. Conclusions: The effect of hardening was maintained in the vast majority of subjects, obtaining a good benefit with no PLE episodes during all the summer. We demonstrate that our standard protocol is effective, and produces a successful outcome for the majority of PLE subjects. Our protocol is shorter than those currently applied, being favourable both for the patient and the physician (AU)

Introducción: La erupción polimorfa lumínica (EPL) es una fotodermatosis idiopática que se presenta típicamente en forma de lesiones papulares o pápulo-vesiculosas pruriginosas en áreas fotoexpuestas, típicamente entre primavera y otoño. En la mayoría de pacientes la EPL es leve, y se previene mediante el uso de fotoprotectores y una exposición gradual a la luz solar. En algunos casos la EPL es muy florida, y requiere una desensibilización profiláctica en primavera, que induce fenómeno de hardening. Objetivo: Describir y evaluar la eficacia de un protocolo de desensibilización que se basa en la administración de UVB de banda estrecha, 2 veces a la semana, durante un mes. Resultados: Se trataron un total de 15 sujetos con el protocolo de desensibilización entre los años 2014 y 2015. Se realizaron un total de 24 tratamientos. El efecto hardening se mantuvo en el 87,5% de los casos tratados. Se encontró una asociación estadísticamente significativa (p<0,05) entre los años de progresión de la enfermedad y la respuesta al tratamiento. Conclusiones: Los efectos del hardening se mantuvieron en la mayoría de los sujetos, los cuales presentaron un buen control de la EPL y ausencia de brotes durante el verano. Se demuestra la efectividad del protocolo de desensibilización en los sujetos con EPL, el cual tiene una duración más corta que los previamente descritos en la literatura (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.

A double-blind randomized controlled trial to assess the efficacy of daylight photodynamic therapy with methyl-aminolevulinate vs. Placebo and daylight in patients with facial photodamage / Ensayo clínico aleatorio controlado, doble ciego para valorar la eficacia de la terapia fotodinámica con luz de día con metilaminolevulinato frente a placebo y luz de día en pacientes con fotodaño facial

BACKGROUND: Daylight PDT (dPDT) is easy to use and does not require light equipment. Such therapy has been exhaustively proved to be successful in the treatment of actinic keratosis, but its use in skin photodamage remains unclear. OBJECTIVE: To evaluate dPDT's efficacy in skin facial photodamage. PATIENTS AND METHODS: This was a parallel-group double-blind, randomized placebo-controlled trial. Sixty participants with symmetric facial photodamage were allocated to topical methyl aminolevulinate (MAL) and daylight vs. matching placebo and daylight. Primary outcome was global photodamage improvement/failure 1 month after the third session. Secondary outcomes included: pain evaluation; specific photodamage severity scores; sun irradiance quantification and Skindex-29 scores. Adverse events were also investigated. RESULTS: Primary analysis included all randomized patients. All patients sun-exposed for 120min in 3 sessions. The risk of failure was lower in the MAL-dPDT group than in the placebo plus daylight group (RR: 0.18; 95% CI: 0.08-0.41). Mean solar irradiance (W/m2) during the first, second and third sessions was 480.82, 430.07 and 435.84, respectively. Items 5 and 14 of Skindex-29 in the MAL-dPDT group showed statistical significant differences. Two patients in the MAL-dPDT group had serious and non-serious events not directly related to the product. CONCLUSION: dPDT with MAL was un-painful, effective and safe for the treatment of facial photodamage. Herpes simplex prophylaxis should be considered before sessions)

INTRODUCCIÓN: La terapia fotodinámica con luz-día (TFDd) es fácil de usar y no requiere de equipo alguno. Tal terapia ha demostrado ser útil en el tratamiento de las queratosis actínicas, pero su uso en el fotodaño no es claro. OBJETIVO: Evaluar la eficacia de la TFDd en el fotodaño facial. Pacientes y MÉTODOS: Se realizó un ensayo clínico doble-ciego controlado con placebo y con asignación aleatoria. Sesenta participantes con fotodaño facial simétrico se asignaron a recibir bien TFD con Metil-Aminolevulinato (MAL) y luz de día o placebo y luz de día. El resultado primario fue la mejoría/fracaso en el fotodaño facial global un mes después de la tercera sesión. Los resultados secundarios incluyeron: dolor; fotodaño específico, irradiancia recibida y la puntuación en el Skindex-29. RESULTADOS: Todos los pacientes se expusieron a la luz de día durante 120 minutos en 3 sesiones. El riesgo de fracaso fue menor en el grupo de TFD con MAL y luz de día que en el grupo placebo (RR:0,18; 95%; IC:0,08 a 0.41). La media de la irradiancia solar (W.m-2) durante la primera, segunda y tercera sesión fue de 480,82, 430,07 y 435,84, respectivamente. Los ítems 5 y 14 del Skindex-29 en el grupo de TFDd con MAL mostraron diferencias estadísticamente significativas. Dos pacientes en el mismo grupo presentaron eventos adversos serios y no serios pero estos no tuvieron relación directa con el producto evaluado. CONCLUSIÓN: La TFDd con MAL fue es un tratamiento indoloro, eficaz y seguro para el tratamiento del fotoenvejecimiento facial. La profilaxis del Herpes simple debe ser considerada antes de cada sesión

[Methotrexate-associated photosensitization]. / Photosensibilisierung durch Methotrexat.

BACKGROUND: Methotrexate (MTX), alongside fumaric acid esters, is the most commonly used drug in the systemic therapy of psoriasis in Germany. It is sometimes used in combination with topical therapy and/or phototherapy due to synergistic effects. CASE REPORT: Here we describe a case of phototoxic dermatitis during treatment with MTX. Other cutaneous side effects of MTX include so-called UV recall, radiation recall, and skin tumor formation.

Terapia fotodinámica con luz de día en España: ventajas y limitaciones / Daylight-Mediated Photodynamic Therapy in Spain: Advantages and Disadvantages

La terapia fotodinámica (TFD) constituye una alternativa terapéutica para las queratosis actínicas, la enfermedad de Bowen y determinados carcinomas basocelulares. Se utiliza además para el tratamiento de otras enfermedades cutáneas de diversa naturaleza, incluyendo enfermedades inflamatorias e infecciosas. Los principales inconvenientes de la TDF convencional son el tiempo que consume su realización (al paciente y al personal sanitario) y el dolor que produce. Recientemente se ha descrito la TFD con luz de día (TFDLD) como alternativa al procedimiento convencional. En diversos estudios se ha mostrado similar en eficacia y mejor tolerada que la TFD clásica en el tratamiento de queratosis actínicas leves-moderadas. No obstante, la mayoría de los estudios realizados proceden del norte de Europa, y no existen por ahora resultados en países de la latitud de España. El presente artículo revisa los principales estudios publicados hasta el momento, expone el protocolo de utilización y resume nuestra experiencia en un grupo de pacientes tratados

Photodynamic therapy (PDT) is an option for the treatment of actinic keratosis, Bowen disease, and certain types of basal cell carcinoma. It is also used to treat various other types of skin condition, including inflammatory and infectious disorders. The main disadvantages of PDT are the time it takes to administer (both for the patient and for health professionals) and the pain associated with treatment. Daylight-mediated PDT has recently been reported to be an alternative to the conventional approach. Several studies have shown it to be similar in efficacy to and better tolerated than classic PDT for the treatment of mild to moderate actinic keratosis. Nevertheless, most of these studies are from northern Europe, and no data have been reported from southern Europe. The present article reviews the main studies published to date, presents the treatment protocol, and summarizes our experience with a group of treated 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.

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.

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.

Chronic actinic dermatitis: two patients with successful management using narrowband ultraviolet B phototherapy with systemic steroids.

BACKGROUND: Chronic actinic dermatitis (CAD) is a debilitating photodermatosis with characteristic clinical, histological and photobiological features (reduced minimal erythema dose: MED). Its management involves various therapeutic approaches, among them there is phototherapy. Efficacy of psoralen ultraviolet therapy (PUVA therapy) was previously demonstrated but there are no current data on the use of narrowband ultra violet B (UVB) therapy (NB-UVB) in CAD. NB-UVB has already been proven to be effective and safe in several other photodermatoses. CASE REPORTS: We report here two dark-skinned patients (skin type IV and V) with CAD, successfully treated with an incremental regimen of NB-UVB phototherapy coupled to a 3 month-course of systemic steroids (1mg/Kg/day). CONCLUSION: Our protocol of NB-UVB with steroids seems to be effective for the management of CAD with a good short term safety profile.

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.

[Avene-50 and Ebastine in treatment and prevention of photodermatosis].

The clinical efficacy of antihistaminic preparation "Kestine" (Ebastine) in combined treatment of 50 patients suffering from photo-allergic dermatosis (15 - solar urticaria, 20 - solar erythema and 15 - solar eczema) are evaluated. Kestine in dosage of 10 mg a day was prescribed in duration of 10 days. Itch disappearance was observed in 87% of patients, reduction of itching - in 10% and in 3% of patients an itch was remain. Photo protector Avene-50 as sunburn preparation, assigned for different type of skins, has been used. This preparation fit for different demands (including prevention of both beginnings and exacerbation of photo allergic reactions) of patients. Water- and sweat-resistance of Avene-50 formula has been taken in account. Treatment caused increasing of some indices of non specific reactions (Kavetski skin test) that confirms recovery of conjunctive tissue elements' activity. Efficacy and safety of this combined method of photodermatosis treatment allow us to use it widely in dermatologic clinic.

Solar urticaria.

Solar urticaria is a relatively rare immunoglobulin E-mediated photodermatosis that is caused by specific, yet diverse wavelengths of light. The history, epidemiology, clinical manifestations, histology, etiology/pathogenesis, differential diagnosis, treatment, course, and prognosis of solar urticaria are reviewed herein.

Polymorphous light eruption.

Polymorphous light eruption is the most common photodermatosis, with a prevalence of as high as 10-20% in Western Europe and in the USA. It starts during the second and third decades of life. Although not life-threatening it can severely impair the quality of life, in particular during leisure activities and in outdoors workers. Polymorphous light eruption belongs to the group of so-called idiopathic photodermatoses. This term denotes dermatoses that occur in otherwise healthy individuals from exposure to sunlight or artificial light without the intervention of an exogenous photosensitizing agent. These diseases have two factors in common: they are precipitated by ultraviolet or visible radiation; and their exact pathomechanism remains obscure but is presumably immunologic in nature.