Oral Nicotinamide for Actinic Keratosis Prevention in Kidney Transplant Recipients: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Oral nicotinamide (NAM) has shown promise in preventing actinic keratoses (AKs) in trials based outside of the United States. We assessed the efficacy of oral NAM supplementation in kidney transplant recipients with a history of keratinocyte carcinoma. MATERIAL AND METHODS: Patients enrolled in a 2-week run-in phase, during which NAM 1000 mg was taken twice daily. After a washout period, patients who tolerated the run-in phase were randomized to NAM 500 mg twice daily or placebo. At baseline, 4, 8, and 12 months, dermatologists conducted full-body skin exams to document area-specific AKs. Routine lab work was collected to ensure the stability of renal allograft function. RESULTS: The dosage was reduced from 1000 to 500 mg due to gastrointestinal symptoms in the run-in phase. Patients were randomized to NAM (n = 10) or placebo (n = 11). At 12 months, mean AK count was 30.8 (95% CI -11.7-73.4) for NAM and 26.6 (95% CI 10.8-42.5) for placebo. The difference in percent AK count change at 12 months compared with baseline was 259.8% (95% CI -385.9 to 905.5) for NAM and 72.4% (95% CI -118.6 to 263.5) for placebo. The between-group difference in percent AK change was not significant (P = .38). There was no attrition in the placebo group and 40% attrition in the NAM arm. DISCUSSION: Nicotinamide did not decrease AK development among kidney transplant recipients. Limitations include drug tolerability, small sample size, and single-center trial nature.

Plum-blossom needle tapping enhances the efficacy of ALA photodynamic therapy for facial actinic keratosis in Chinese population: a randomized, multicenter, prospective, and observer-blind study.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a reliable treatment for actinic keratosis (AK), but its effect needs to be enhanced in thick lesions. Plum-blossom needle is a traditional Chinese cost-effective instrument for enhancing the transdermal delivery of ALA. However, whether it could improve the efficacy of AK treatment has not yet been investigated. OBJECTIVE: To compare the efficacy and safety of plum-blossom needle-assisted PDT in facial AK in the Chinese population. METHODS: In this multicenter, prospective study, a total of 142 patients with AKs (grades I-III) were randomized into the plum-blossom needle-assisted PDT group (P-PDT) and control PDT group (C-PDT). In the P-PDT group, each AK lesion was tapped vertically by a plum-blossom needle before the application of 10% ALA cream. In the C-PDT group, each lesion was only wiped with regular saline before ALA cream incubation. Then, 3 hours later, all the lesions were irradiated with light-emitting diode (LED) at a wavelength of 630 nm. PDT was performed once every 2 weeks until all lesion patients achieved complete remission or completed six sessions. The efficacy (lesion response) and safety (pain scale and adverse events) in both groups were evaluated before each treatment and at every follow-up visit at 3-month intervals until 12 months. RESULTS: In the P-PDT and C-PDT groups, the clearance rates for all AK lesions after the first treatment were 57.9% and 48.0%, respectively (P < 0.05). For grade I AK lesions, the clearance rates were 56.5% and 50.4%, respectively (P = 0.34). For grade II AK lesions, the clearance rates were 58.0% and 48.9%, respectively (P = 0.1). For grade III AK lesions, the clearance rates were 59.0% and 44.2%, respectively (P < 0.05). Moreover, grade III AK lesions in the P-PDT group required fewer treatment sessions (P < 0.05). There was no significant difference in the pain score between the two groups (P = 0.752). CONCLUSION: Plum-blossom needle tapping may enhance the efficacy of ALA-PDT by facilitating ALA delivery in the treatment of AK.

Pharmacological Agents Used in the Prevention and Treatment of Actinic Keratosis: A Review.

Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.

Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial.

BACKGROUND: In mouse models of skin cancer, high-dose oral vitamin D3 (VD3; cholecalciferol) combined with photodynamic therapy (PDT) can improve the clearance of squamous precancers (actinic keratoses [AKs]). OBJECTIVE: To determine whether oral VD3 can improve the clinical efficacy of a painless PDT regimen in humans with AK. METHODS: The baseline lesion counts and serum 25-hydroxyvitamin D3 levels were determined. In group 1, 29 patients underwent gentle debridement and 15-minute aminolevulinic acid preincubation with blue light (30 minutes; 20 J/cm2). In group 2, 29 patients took oral VD3 (10,000 IU daily for 5 or 14 days) prior to debridement and PDT. Lesion clearance was assessed at 3 to 6 months. RESULTS: In group 1, the mean clearance rates of facial AK were lower in patients with VD3 deficiency (25-hydroxyvitamin D3 level < 31 ng/dL; clearance rate, 40.9% ± 42%) than in patients with normal 25-hydroxyvitamin D3 levels (62.6% ± 14.2%). High-dose VD3 supplementation (group 2) significantly improved the overall AK lesion response (72.5% ± 13.6%) compared with that in group 1 (54.4% ± 22.8%). No differences in side effects were noted. LIMITATIONS: Nonrandomized trial design (interventional cohort matched to registry-based controls). CONCLUSIONS: Oral VD3 pretreatment significantly improves AK clinical responses to PDT. The regimen appears promising and well tolerated.

Actinic keratosis: where do we stand and where is the future going to take us?

Introduction: Actinic keratosis (AK) is a chronic disease which is mainly located across areas of sun-exposed skin. Clinical and subclinical lesions coexist across a large area resulting in a field cancerization. As these lesions have the potential to transform into invasive squamous cell carcinoma (iSCC), treatment is crucial. With global prevalence increasing, AK is expected to be the most common in situ carcinoma of the skin.Areas covered: In this article, we cover the established algorithm of treating AK and give an insight into the drugs under development. There are six compounds under development covering different treatment angles, from Sinecatechin a Polyphenon E which targets the link between HPV infection and development of AK, over Tirbanibulin which targets the SRC proto-oncogene and fast proliferating cells, to Tuvatexib a small-molecule dual VDAC/HK2 modulator that has shown that it can compete with the established therapies.Expert opinion: These new treatment options are moving us further toward a more individually tailored treatment for each patient considering his abilities, the size and location of his lesions but also the genetic bases as well as individual risk of transforming into a iSCC and possibly other factors contributing to each patients individual AK lesions.

Photodynamic therapy activated by intense pulsed light in the treatment of actinic keratosis.

BACKGROUND: Actinic keratosis (AK), a hyperkeratotic lesion induced by solar exposure, is the precancerous lesion that most frequently develops into squamous cell carcinoma. Cryotherapy, topical fluorouracil 5, topical diclofenac 3% gel and, more recently, ingenol mebutate are used in addition to surgery. However, these treatments have varying degrees of effectiveness and are not always tolerated due to side effects. In recent years, photodynamic therapy (PDT), has asserted itself as a new effective and safe method for the treatment of actinic keratoses with almost no side effects. The aim of this study is to verify whether a third treatment may now be added to the "Conventional -PDT" and "Daylight-PDT": PhotoDynamic Therapy activated by Intense Pulsed Light (IPL-PDT). METHODS: Thirty-one patients, 24 males and 7 females, in most cases elderly, were included in the trial. As in the previous methods, also in IPL-PDT, 5-methylaminolevulinic acid (MAL) was applied topically for a period of 3 hours. Thereafter, the occlusive dressing and the topical cream, were removed and the neoformation was irradiated with IPL, with a 640 nm filter with variable power. Irradiation was performed in single or multiple sessions, depending on the type of keratosis, to completely cover the lesion and the apparently healthy surrounding areas, i.e. the cancerization field. RESULTS: Results were evaluated 3, 6 and 9 months after treatment. Treatment achieved a 95% complete clearance rate, with a 5% partial relapse, 9 months after the last treatment. CONCLUSIONS: The above method is a valid alternative to methods already in use. The results obtained demonstrate the efficacy and tolerability of the treatment described which, due to its versatility and speed of use, is preferable to the methods used so far.

Long-term clinical outcomes of imiquimod 5% cream vs. diclofenac 3% gel for actinic keratosis on the face or scalp: a pooled analysis of two randomized controlled trials.

BACKGROUND: Actinic keratosis (AK) is an early in situ epidermal cancer which can progress to invasive squamous cell carcinoma (SCC). Imiquimod 5% cream (IMIQ) and diclofenac 3% gel (DIC) are frequently used to treat AK; however, their long-term effects following repeated treatment cycles have never been compared. OBJECTIVE: To compare IMIQ and DIC in the treatment of AK with respect to the risk of change to grade III AK or invasive SCC, after 3 years. METHODS: Data were pooled from two randomized, active-controlled, open-label, multicentre, multinational, phase IV studies (Clinicaltrials.gov NCT00777127/NCT01453179), with two parallel groups. Studies were conducted between 2008 and 2015 and were almost identical in design. Patients eligible for inclusion were immunocompetent adults with 5-10 visible AK lesions on the face/scalp and grade I/II AK. The primary endpoint was inhibition of histological change to grade III AK or invasive SCC in the study treatment area, observed until month 36. Patients applied either IMIQ or DIC for a maximum of six treatment cycles. RESULTS: In total, 479 patients (IMIQ 242; DIC 237) were included in the full analysis set. Histological change to grade III AK or invasive SCC was observed until month 36 in 13 (5.4%) patients treated with IMIQ, compared with 26 (11.0%) patients treated with DIC (absolute risk difference -5.6% [95% confidence interval -10.7%, -0.7%]). Time to histological change was greater in the IMIQ group than the DIC group (P = 0.0266). Frequency of progression to invasive SCC was lower with IMIQ than with DIC at all time points. Initial clearance rate was higher in the IMIQ group compared with the DIC group, while recurrence rate was lower. Both treatments were well tolerated. CONCLUSIONS: Over 3 years, IMIQ was superior to DIC in clearing AK lesions and preventing histological change to grade III AK or invasive SCC and recurrence.

Single Ablative Fractional Resurfacing Laser Treatment For Forearm Actinic Keratoses: 6-Month Follow-Up Data From An Intrapatient Comparison Between Treated and Untreated Sites.

BACKGROUND AND OBJECTIVES: Actinic keratoses (AK) are common pre-cancerous lesions, which are associated with ultraviolet light exposure and aging. Wounding therapies such as fractionated laser resurfacing (FLR) have been previously demonstrated to effectively treat facial AK. However, the effectiveness of FLR on other sites commonly afflicted with AK has not been studied in detail. Previously, our group has reported that treatment of aged skin with wounding therapies including dermabrasion and ablative fractionated resurfacing results in the removal of senescent fibroblasts and normalizing the pro-carcinogenic acute ultraviolet B radiation responses associated with aged skin. The current studies were designed to test the effectiveness of FLR of the forearm skin of subjects aged 60 and older to remove AKs. STUDY DESIGN/MATERIALS AND METHODS: Between February 2018 and March 2019, 30 subjects were enrolled in a study, in which they underwent a single FLR treatment of one extremity including the dorsal forearm, wrist, and dorsal hand. The number of AKs was recorded on both extremities at baseline, 3 and 6 months in a blinded fashion. Side effects of the FLR were documented. RESULTS: A single FLR treatment resulted in a 62% reduction in the absolute number of AK in the treated arm at 6 months post-treatment. The laser treatment was well-tolerated without major complications. CONCLUSIONS: These studies demonstrate that FLR using settings, which have demonstrated to remove senescent fibroblasts and normalize the pro-carcinogenic UVB-response of aged skin is a potentially effective and safe field therapy treatment that should be studied for long-term efficacy for use in treating upper extremity AKs. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Low-level light-assisted photodynamic therapy using a wearable cap-like device for the treatment of actinic keratosis of the scalp.

BACKGROUND: Daylight photodynamic therapy (dlPDT) is a painless and increasingly cost-effective treatment for actinic keratosis (AK). New protocols avoid incubation, minimizing pain and adverse events. However, it is time-consuming and dependent on specific weather conditions. In patients with AK of the scalp, we evaluated the efficacy of indoor photodynamic therapy (PDT) using a wearable low-level light therapy (LLLT) device, without pre-incubation with a photosensitizing agent. METHODS: In this pilot study, 27 patients with thin and moderately thick AK (Olsen Grades I-II) underwent a single 15-minute session of LLLT using a wearable cap-like device immediately after application of methyl-aminolevulinate (MAL) cream, with no prior preparation of the affected area. Treatment efficacy was quantified by measuring the reduction in AK lesion number and the AK quality of life (AKQoL) score. All AK lesions were mapped at baseline for follow-up 2 months later. Paired pre/post scalp biopsies from 5 patients were analysed using histological and immunohistochemical techniques (p53, p27, cyclin D1, p63, and Ki67 expression). Data were analysed using the Wilcoxon signed-rank test. RESULTS: In all patients we observed a global reduction in the number of AK lesions (71%; p < 0.0001) and AKQoL score (from 5.6 to 4.4; p = 0.034) 2 months after treatment. Histology and immunohistochemistry of skin biopsies from 5 patients also revealed marked improvements after LLLT. No patients reported any pain during treatment. CONCLUSION: PDT using LLLT is a rapid, painless, and efficacious modality for the treatment of AK.

Local interventions for actinic keratosis in organ transplant recipients: a systematic review.

BACKGROUND: Actinic keratosis (AK) in organ transplant recipients (OTRs) has a high risk of progressing to invasive squamous cell carcinoma of the skin. Thus, early and consequent treatment of AKs is warranted in OTRs. OBJECTIVES: To summarize the current evidence for nonsystemic treatments of AKs in OTRs. METHODS: We performed a systematic literature search in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) and hand-searched pertinent trial registers up to 22 August 2018. Randomized controlled trials (RCTs) evaluating nonsystemic interventions for AKs in OTRs were included. The risk of bias was estimated using the Cochrane Risk of Bias Tool. RESULTS: Of 663 records initially identified, eight RCTs with 242 OTRs were included in a qualitative synthesis. Most studies evaluated methyl aminolaevulinate photodynamic therapy (MAL-PDT), followed by ablative fractional laser (AFXL) and diclofenac sodium 3% in hyaluronic acid, imiquimod 5% cream and 5-fluorouracil 5% cream (5-FU). MAL-PDT showed the highest rates of participant complete clearance (40-76·4%), followed by imiquimod (27·5-62·1%), diclofenac (41%) and 5-FU (11%). Similar results were observed for lesion-specific clearance rates. Treatment with AFXL alone revealed low lesion clearance (5-31%). Local skin reactions were most intense in participants treated with a combination of AFXL and daylight MAL-PDT. There were no therapy-related transplant rejections or worsening of graft function in any trial. The overall risk of bias was high. CONCLUSIONS: Limited evidence is available for the treatment of AKs in OTRs. MAL-PDT is currently the best-studied intervention. Lesion-specific regimens may not be sufficient to achieve disease control. Field-directed regimens are preferable in this high-risk population.

Efficacy and safety of topical SR-T100 gel in treating actinic keratosis in Taiwan: A Phase III randomized double-blind vehicle-controlled parallel trial.

BACKGROUND: Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. OBJECTIVES: To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. METHODS: A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. RESULTS: 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p < 0.001). Severe local reactions were reported by only one subject using SR-T100. CONCLUSION: The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK.

Efficacy of iontophoresis-assisted ablative fractional laser photodynamic therapy with short incubation time for the treatment of actinic keratosis: 12-month follow-up results of a prospective, randomised, comparative trial.

BACKGROUND: Iontophoresis is a transdermal drug-delivery technique that enhances the transport of ionic species across membranes and may have significant benefit for the treatment of actinic keratosis (AK) by ablative fractional laser-primed photodynamic therapy (AFL-PDT). The aims of this study were to compare the efficacy, recurrence rate, cosmetic outcome and safety of iontophoresis-assisted AFL-PDT with 2h of incubation vs. those of conventional AFL-PDT with 2- and 3-h incubation in patients with facial and scalp AK. METHODS: Patients were randomly assigned to iontophoresis-assisted AFL-PDT with a 2-h incubation time (group A) and conventional AFL-PDT with a 2-h (group B) and 3-h (group C) incubation time. All patients underwent AFL-PDT, and group A patients were assigned to treatment with iontophoresis after methyl-aminolevulinate (MAL) application. After 2 or 3h, MAL-applied lesions were irradiated using a red light. Patients were followed up at 1-week, 3 months and 12 months after treatment. Efficacy, cosmetic outcomes and adverse events were assessed. RESULTS: In total, 41 patients (160 AK lesions) completed the study and were evaluated. Efficacy was significantly higher in Group A (88.7%) than in Group B (73.2%); the efficacy of groups A and C (92.2%) at 3 months follow-up was comparable. The recurrence rates were not significantly different between the groups at 12 months (P=0.841). The three groups did not differ in terms of cosmetic outcomes and safety. CONCLUSIONS: Iontophoresis-assisted AFL-PDT showed higher efficacy than AFL-PDT with short incubation time. Iontophoresis may effectively reduce the incubation time in AFL-PDT.

Plum-blossom needling promoted PpIX fluorescence intensity from 5-aminolevulinic acid in porcine skin model and patients with actnic keratosis.

BACKGROUND AND OBJECTIVES: Plum-blossom needling might enhance transdermal penetration of topically applied drugs by creating vertical channels. The purpose of this study was to evaluate drug delivery assisted by plum-blossom needling comparing with CO2 laser ablative fractional resurfacing (AFR) using 5-aminolevulinic acid (5-ALA), a porphyrin precursor, as a test drug. MATERIALS AND METHODS: Ex vivo porcine skin was treated with plum-blossom needle(HWATO, Suzhou medical supplies factory Co., Ltd. China) or CO2 laser AFR before topical application of 20% 5-ALA(Sigma-Aldrich, Co., USA)cream, placebo cream and no cream. ALA-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1800µm. Needling was done by tapping the skin vertically from 5cm high above quickly. AFR was performed with a 10.6µm wavelength prototype CO2 laser, using stacked single pulses of 3 millisecond and 91.6mJ per pulse. Plum-blossom needling after ALA application was also done. Fluorescence intensity on lesion surface was examined by curalux spectrum analyzer (Laser Institute of Munich University, Germany) and VAS pain score was recorded in a randomized split-lesion clinical trial including 6 patients, 8 actinic keratosis lesions. RESULTS: AFR created regular cone-shaped channels surrounded by a 70µm thin layer of thermally coagulated dermis, respectively. The cone is approximately 200µm in diameter at the opening and 1850µm in depth. Plum-blossom needle created irregular cone-shaped channels of approximately 180µm in diameter at the opening and it always drags a tail-which was shaped from the closed deeper channels. There was no porphyrin fluorescence in placebo cream or untreated skin sites. Plum-blossom needling followed by ALA application enhanced drug delivery with significantly higher porphyrin fluorescence at the edge of hole (P<0.005) and 100µm far from the hole (P=0.000) versus AFR followed by ALA application at skin depths of 120 and 500µm. Needling after ALA application presented higher porphyrin fluorescence at the edge of hole at skin depths of 120µm (P<0.005) and lower porphyrin fluorescence at 1000µm deep hole edge, and 100µm far from the hole at 120µm, 500µm and 1000µm depths versus AFR followed by ALA application (P<0.005). Skin massage after ALA application did not affect ALA-induced porphyrin fluorescence after pretreatment of plum-blossom needling or AFR. ALA application after plum-blossom needling was better than before plum-blossom needling. The clinical trial showed that the surface fluorescence intensity was stronger in needle-pretreated-lesion than in laser-pretreated-lesion. While the VAS pain score between needle treatment and laser treatment was almost the same. CONCLUSIONS: Plum-blossom needling facilitates delivery of topical ALA into the dermis. It may help ALA to diffuse a little more broadly than AFR does in superficial dermis and obtain similar clinical effect with a much lower cost. Plum-blossom needling treatment appears to be a clinically practical and economical means for enhancing transdermal delivery of ALA, a photodynamic therapy drug, and presumably many other topical skin medications.

Queilitis actínica: aspectos histológicos, clínicos y epidemiológicos / Actinic cheilitis: histological, clinical and epidemiological characteristics

Introducción: la destrucción de la capa de ozono ha provocado un aumento en la incidencia de lesiones de la piel, a la que se suma la queilitis actínica. Objetivo: describir los aspectos histológicos, clínicos y epidemiológicos de la queilitis actínica a partir de la literatura reciente. Métodos: se revisaron las bases electrónicas PubMed, SciELO y Google Scholar con los términos claves en inglés y español: queilitis, queratosis, actínica, solar. Se incluyeron artículos originales, de revisión, reportes de casos, tesis y libros de la especialidad publicados preferentemente en el período 2005-2014. Resultados: La queilitis actínica es un trastorno potencialmente maligno inducido por la exposición solar y caracterizado por alteraciones micro y macroestructurales del labio. Factores de riesgo que interaccionan con la exposición solar son el fototipo (piel clara), hábito tabáquico, sexo (hombres), edad y ocupación (aire libre). Entre las alteraciones histológicas se encuentran la displasia epitelial y la elastosis solar; sin embargo, la severidad de estas no correlacionan con la gravedad clínica. Los pacientes con queilitis actínica presentan alteraciones de color, descamación, ulceraciones, difuminación del bermellón, entre otras. En muchas ocasiones la consulta y el diagnóstico son tardíos; se realizan cuando el cuadro ha evolucionado a cáncer. El diagnóstico es principalmente clínico, sumado a la biopsia de las lesiones con presentaciones moderadas y severas. Actualmente la terapia incluye métodos quirúrgicos y farmacológicos, y métodos innovadores como la fototerapia. Sin duda, la estrategia de prevención más importante es aumentar el uso de protectores solares, especialmente en la población de alto riesgo ocupacional. Conclusiones: la queilitis actínica es una patología relevante para los países sudamericanos, debido a que los factores de riesgo están presentes diariamente en las actividades de millones de trabajadores de nuestra región, por eso es necesario potenciar la investigación que permita mejorar la prevención, tratamiento y rehabilitación de esta patología(AU)

Introduction: depletion of the ozone layer has brought about an increase in the incidence of skin lesions, including actinic cheilitis. Objective: describe the histological, clinical and epidemiological characteristics of actinic cheilitis based on a review of recent literature. Methods: a search was conducted in the databases PubMed, SciELO and Google Scholar using the descriptors cheilitis, keratosis, actinic, solar, and their counterparts in Spanish. The search included original papers, review papers, case reports, theses and books about the specialty preferably published from 2005 to 2014. Results: actinic cheilitis is a potentially malignant condition induced by sun exposure and characterized by micro- and macrostructural alterations of the lip. The risk factors interacting with sun exposure are the skin phototype (light skin), smoking, gender (male), age and occupation (outdoor jobs). Histological alterations include epithelial dysplasia and solar elastosis, though their severity does not correlate with the degree of clinical seriousness. Patients with actinic cheilitis present color alterations, desquamation, ulceration and blurring of the vermillion border, among other signs and symptoms. On many occasions patients do not seek care during the early stages of the disease. As a result, diagnosis is made when the condition has already evolved into cancer. The diagnosis is basically clinic, with the support of the biopsy of lesions with moderate to severe characteristics. Current therapy includes surgery and medication, as well as innovative techniques like phototherapy. The most important strategy is no doubt the use of sunscreens, especially by the population at high occupational risk. Conclusions: actinic cheilitis is a condition relevant to South American countries, since its risk factors are present in the daily activities of millions of workers from our region. It is therefore necessary to foster research aimed at improving its prevention, treatment and rehabilitation(AU)

Temperature-Modulated Photodynamic Therapy for the Treatment of Actinic Keratosis on the Extremities: A One-Year Follow-up Study.

BACKGROUND: The efficacy of photodynamic therapy (PDT) using topical 5-aminolevulinic acid (ALA) for the treatment of actinic keratosis (AK) is lower on the distal extremities compared with head and neck areas. A recent pilot study demonstrated increased efficacy of ALA PDT when the skin is warmed during ALA incubation. Prolonged clearance rates on the heated extremity were noted in 3 subjects that were evaluated after the study ended. The aim of this study was to evaluate the longevity of clearance rates after temperature-modulated PDT for the treatment of AKs on the extremities. MATERIALS AND METHODS: A total of 18 subjects (20 pairs of extremities) with at least 10 AKs on the upper or lower extremities were enrolled in the single-center study. Twenty percent ALA was applied to both extremities and heated during the 1-hour incubation period, followed by exposure to 10 J/cm 417-nm blue light. Lesions were photographed, counted, and templated at baseline, 1 week, and 3, 6, 9, and 12 months after treatment. RESULTS: A total of 17 subjects completed the 1-year study. The total number of lesions counted at baseline was 724 Grade 1 and 2 AKs (median 15 on each extremity). The lesion count at 3 and 12 months was 70 (9.6%) and 72 (9.9%), respectively. Grade 3 AKs did not resolve with treatment. The median baseline temperature of the treated extremities was 31.6°C. The median maximum temperature during the 1-hour incubation period was 41.2°C. The median clearance at 3 months was 90% and the same was maintained at 12 months. No new AK lesions formed in the treated areas within the 12-month follow-up period. CONCLUSION: Warming the skin after application of ALA is well tolerated, does not increase side effects, and increases the long-term efficacy of PDT for the treatment of AKs. The authors suggest that mild skin warming may both improve efficacy and reduce variability of response to PDT in practice.

Topical AC-11 abates actinic keratoses and early squamous cell cancers in hairless mice exposed to Ultraviolet A (UVA) radiation.

AC-11 is an aqueous extract of the botanical, Uncaria tomentosa, which has a variety of effects that enhance DNA repair and down regulate inflammation. AC-11 is essentially free of oxindole alkaloids (< 0.05%, w/w) but contains more than 8% carboxy alkyl esters (CAEs) as their active ingredients. Three groups of 10 outbred SK-1 hairless or SK-II hairless strains of mice each were treated with AC-11 at 0.5%, 1.5%, and 3.0% in a non-irritating, dye-free, perfume-free, and fragrance-free vanishing cream vehicle. Ten mice used vehicle only and 10 were untreated. Each concentration of AC-11 and was applied daily to the backs of the mice prior to exposure to a 1,600-watt solar simulator used in this work (Solar Light Co. Philadelphia, PA) emitting (mainly Ultraviolet A (UVA) and B (UVB) radiation) duration of the experimental period with UVB wavelengths was filtered out with a 1.0 cm Schott WG 345 filter. AC-11 with a peak absorption at 200nm does act as a sun block. We tested for and focused on clinical appearance of mice and histological appearance of tumors in mice rather than metrics of radiation generated inflammation. Tumor progression scores were assigned as follows: 4+ = extensive tumor development; 3+ = early malignancies (raised palpable plaques)(early squamous cell cancers) 2+ = firm scaling, palpable keratosis (actinic keratoses); 1+ = light scaling with erythema. Following a total cumulative dose of 738 J/cm2, 85.7% all of the irradiated control animals, which did not receive AC-11 had precancerous actinic keratosis (AK)-type lesions (2+) (64.3% versus 42.9%) or early squamous cell carcinoma (SCC) (3+) (21.4% vs. 4.8%), in comparison with 47.7 % of AC-11-treated animals. There were no significant differences between the AC-11 groups. Three months after cessation of exposure to UVA radiation, the lesions in all but three of the 14 animals which were treated with AC-11 that were still evaluable irradiated with UVA radiation progressed to papillomas and frank squamous cell carcinomas (+4 responses). AC-11 retarded, but did not stop, carcinogenesis progression. It is possible that if AC-11 was continuously applied tumors would not have in mice treated with AC-11 for a limited period. While we do not know how AC-11 exerts its DNA repair and anti-inflammatory effects, AC-11 is therapeutic for the treatment at the time of development of actinic keratoses and squamous cell carcinomas in mice and by extension humans. Without the constant presence of AC-11 these protective effects do not occur.

Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) of actinic keratosis (AK) has shown preliminary efficacy and safety results comparable to conventional photodynamic therapy (c-PDT), using methyl aminolevulinate (MAL) cream. OBJECTIVES: To demonstrate the efficacy and safety of DL-PDT vs. c-PDT in treating mild facial/scalp AK. MATERIALS AND METHODS: This 24-week randomized, controlled, investigator-blinded, multicentre, intra-individual efficacy (non-inferiority) and safety (superiority regarding pain) study enrolled 100 subjects. AKs on the face/scalp were treated once, with DL-PDT on one side and c-PDT on the contralateral side. Primary end points for DL-PDT at week 12 were efficacy [non-inferiority regarding complete lesion response (mild AK)] and safety (superiority regarding subject's assessment of pain). Lesions with complete response 12 weeks after one treatment session were followed until week 24. The safety evaluation included incidence of adverse events. Subject satisfaction was classified using a questionnaire. RESULTS: At week 12, the complete lesion response rate with DL-PDT was non-inferior to c-PDT (89·2% vs. 92·8%, respectively; 95% confidence interval -6·8 to -0·3), confirmed by intention-to-treat analysis. Additionally, regardless of the treatment used, 96% of mild lesions were maintained in complete response 24 weeks after the PDT session. For DL-PDT, subject-reported pain was significantly lower (0·8 vs. 5·7, respectively; P < 0·001), with better tolerability and significantly higher subject satisfaction regarding convenience and outcome. CONCLUSIONS: Daylight-mediated PDT was not inferior in efficacy to Metvix c-PDT (mild AK response rate), better tolerated, nearly painless and more convenient for patients.

[Actinic keratosis: when is a skin biopsy necessary?]. / Kératoses actiniques : quand biopsier ?

The diagnosis of actinic keratosis is generally established by clinical examination. However, actinic keratosis can progress into an invasive squamous cell carcinoma, therefore biopsy and histological examination may be needed. The risk of progression into an invasive carcinoma is not well established; it varies in the literature between 0.025% and 20% for a given lesion. Some clinical aspects suggest transformation into an invasive carcinoma; they include inflammation, induration, size > 1 cm, rapid enlargement of the lesion, bleeding or ulceration, and should prompt the clinician to perform a skin biopsy. In case of resistance after a well-driven treatment, a biopsy may be necessary. Finally, in cases of atypical clinical aspect, a biopsy may be useful in order to obtain a correct diagnosis.

Nonablative fractional photothermolysis for facial actinic keratoses: 6-month follow-up with histologic evaluation.

BACKGROUND: A number of epidermal and papillary dermal skin conditions can be treated safely and effectively with fractional photothermolysis (FP). OBJECTIVE: We sought to evaluate the effectiveness of FP with a 1550-nm fractionated erbium-doped fiber laser for the treatment of facial actinic keratoses (AKs). METHODS: Fourteen men, ages 59 to 79 years, underwent 5 laser treatments (2- to 4-week intervals) at an energy fluence of 20 to 70 mJ and treatment level of 11 (8-10 passes), corresponding to 32% to 40% surface area coverage. AK counts and photographs were taken at baseline, before each treatment, and at 1-, 3-, and 6-month follow-ups after the last treatment. Biopsies were performed at baseline and at the 3-month follow-up. The clinical improvement of the actinic lesions was evaluated by a dermatologist using digital photography and lesion counts at all 3 follow-up visits. RESULTS: The AK count for each patient was reduced on average by 73.1% (67.5%-77.7%) at the 1-month, 66.2% (60.0%-71.5%) at the 3-month, and 55.6% (43.9%-64.8%) at the 6-month follow-up visit. Excluding two cases, all biopsy specimens (baseline and at the 3-month follow-up) were positive for histologic features of AK and/or squamous cell carcinoma. LIMITATIONS: This study is limited by a small number of patients; therefore further clinical studies are warranted. CONCLUSIONS: FP decreases the number of clinical AKs; however, posttreatment biopsy specimens indicate the histologic persistence of AKs (epidermal tumors). FP is not an adequate single-treatment modality for AKs.

Modes of action of diclofenac 3%/hyaluronic acid 2.5% in the treatment of actinic keratosis.

BACKGROUND: The efficacy of topically applied diclofenac 3 % in combination with hyaluronic acid 2.5 % in the treatment of actinic keratoses (AKs) has been demonstrated in several clinical studies, but the exact mode of action is still unclear. This study evaluates the potential molecular and cellular main modes of action of topically applied diclofenac in the treatment of AKs. PATIENTS AND METHODS: In this prospective study 20 male patients with AKs were treated for 90 days with topically applied diclofenac 3 %/hyaluronic acid 2.5 %. Before and after treatment, skin biopsies were taken from the treatment area and were investigated histologically and immunohistochemically as well as compared to healthy skin. For this purpose, markers for inflammation (COX-2, CD3, CD8), apoptosis (p53), cell cycle arrest (p53, p21), proliferation (Ki67), and angiogenesis (CD31) were examined. RESULTS: The immunohistochemical analysis demonstrated a significant decrease in expression of COX-2, CD3 and CD8. Furthermore, there was a clear reduction of CD31 expression as a marker for angiogenetic processes. Additionally, there was a tendency toward a reduction in markers for proliferation and apoptosis. CONCLUSIONS: The efficacy of diclofenac 3 %/hyaluronic acid 2.5 % in the treatment of AKs is probably due to anti-inflammatory and anti-angiogenic effects, potentially associated with anti-proliferative and apoptosis-inducing underlying mechanisms.