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.

[The perception of care received by patients with actinic keratosis]. / La percepción del proceso asistencial de pacientes con queratosis actínica.

OBJECTIVE: To analyse barriers limiting an integral approach in the care process of patients with actinic keratosis, and to validate a questionnaire of their perception in order to assess this approach. METHOD: A qualitative study (Focus Group) was conducted to assess the perception of the healthcare process of professionals (dermatologists, family doctors, nurses, pharmacists and managers), and patients. A validation study of a new tool was conducted, defining the scope and contents of a questionnaire of perceived quality. Reliability, consistency and validity were analysed after inviting a convenience sample of 225 patients to respond. RESULTS: Underdiagnosis in primary care, a higher variability in resources, and access to the health care circuit, together with gaps in patient information about actinic keratosis, are relevant barriers to achieve comprehensive care in this disease condition. The result of the focus groups advised to elaborate 14 reactive items. A total of 224 patients responded (mean age 71.6, SD 11.1), of which 153 (68%) were men. Two factors were isolated including 12 items (explained variance of 58%). The consistency of this factorial solution was .87, the split-half reliability being .76, with the scores in the factors showing an adequate predictive capacity. CONCLUSIONS: The coordination between levels and to reduce to variability in equipment and clinical decision making in Primary Care are the most prominent barriers. The questionnaire has appropriate metric properties and it explores the information and care by the medical staff and the information and advice provided by the pharmacist.

Efficacy, Safety, and Tolerability of 4% 5-Fluorouracil Cream in a Novel Patented Aqueous Cream Containing Peanut Oil Once Daily Compared With 5% 5-Fluorouracil Cream Twice Daily: Meeting the Challenge in the Treatment of Actinic Keratosis.

BACKGROUND: Actinic keratosis (AK) is a neoplastic keratosis and a precursor of squamous cell carcinoma (SCC). OBJECTIVE: We are presenting data on a novel formulation of 4% 5-Fluorouracil (5-FU) in an aqueous vehicle cream containing peanut oil (Tolak) with once daily application versus treatment with 5% 5-FU twice daily for 4 weeks. METHODS: 1) A dose ranging study of 4% 5-FU cream once or twice daily for 2 or 4 weeks and its vehicle, compared to 5% 5-FU cream twice daily for 4 weeks in 121 subjects. 2) A double-blinded multicenter study involving 841 subjects for non-inferiority and safety of 4% 5-FU cream once daily vs 5% 5-FU cream twice daily over 4 weeks with 100% and 75% clinical clearance of AK's. RESULTS: 4% 5-FU qd q4wks achieved 100% clearance in 80% and 75% clearance in 100% of subjects vs 75% and 95% respectively with 5% 5-FU bid q4wks. 4% 5-FU qd2wks achieved 100% clearance in 60% and 75% clearance in 85% of subjects. 4% 5-FU qd q4wks recorded 65 adverse events and 30% application site skin irritation versus 71 events and 60% with 5% 5-FU bid q4wks. 4% 5-FU exceeded non-inferiority by 1.32% with sub-analysis for higher percentage of severely affected patients. 4% 5-FU showed 75% clearance of AK's in 80.5% vs 80.2% for 5% 5-FU with superior tolerability. CONCLUSIONS: 4% 5-FU cream is a novel, efficacious, superior tolerated once daily topical treatment for better compliance and treatment outcome. The peanut oil component is safe even in peanut-allergic patients.

J Drugs Dermatol. 2016;15(10):1218-1224.

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

Managing actinic keratosis in primary care.

Actinic, or solar, keratosis is caused by chronic ultraviolet-induced damage to the epidermis. In the UK, 15-23% of individuals have actinic keratosis lesions. Risk factors include: advanced age; male gender; cumulative sun exposure or phototherapy; Fitzpatrick skin phototypes I-II; long-term immuno-suppression and genetic syndromes e.g. xeroderma pigmentosum and albinism. Actinic keratoses are regarded by some authorities as premalignant lesions that may transform into invasive squamous cell carcinoma (SCC) and by others as in situ SCC that may progress to an invasive stage. The risk of malignant change appears low; up to 0.5% per lesion per year. Up to 20-30% of lesions may spontaneously regress but in the absence of any reliable prognostic clinical indicators regarding malignant potential active treatment is considered appropriate. Actinic keratosis lesions may present as discrete hyperkeratotic papules, cutaneous horns, or more subtle flat lesions on sun-exposed areas of skin. The single most helpful diagnostic sign is an irregularly roughened surface texture: a sandpaper-like feel almost always indicates actinic damage. Dermatoscopy can be helpful in excluding signs of basal cell carcinoma when actinic keratosis is non-keratotic. It is always important to consider the possibility of SCC. The principal indication for referral to secondary care is the possibility of cutaneous malignancy. However, widespread and severe actinic damage in patients who are immunosuppressed is also a reason for referral.

Laser-mediated Photodynamic Therapy: An Alternative Treatment for Actinic Keratosis?

Photodynamic therapy (PDT) with light emitting diode (LED) illumination is a frequently used treatment modality for actinic keratosis (AK) with excellent cosmetic outcome. A major disadvantage, however, is the high pain score. Pulsed dye laser (PDL) illumination has been suggested, but the long-term efficacy of this treatment is unknown. In this split-face study we prospectively treated 61 patients with AK, with both LED-PDT and PDL-PDT. The mean change in the number of lesions between the end of follow-up and start of therapy was -4.25 (95% confidence interval (95% CI) -5.07; -3.43) for LED-PDT and -3.88 (95% CI -4,76; -2.99) for PDL-PDT, with a non-significant difference (p = 0.258) of -0.46 (95% CI -1.28; 0.35). The percentage decrease from baseline in the total number of AK was 55.8% and 47.8%, respectively, at 12-month follow-up. Visual analogue scale pain score was lower after PDL (mean 2.64) compared with LED illumination (mean 6.47). These findings indicate that PDL-PDT is an effective alternative illumination source fo.

Photodynamic Therapy for Actinic Keratoses: A Randomized Prospective Non-sponsored Cost-effectiveness Study of Daylight-mediated Treatment Compared with Light-emitting Diode Treatment.

Daylight-mediated photodynamic therapy (DL-PDT) is considered as effective as conventional PDT using artificial light (light-emitting diode (LED)-PDT) for treatment of actinic keratoses (AK). This randomized prospective non-sponsored study assessed the cost-effectiveness of DL-PDT compared with LED-PDT. Seventy patients with 210 AKs were randomized to DL-PDT or LED-PDT groups. Effectiveness was assessed at 6 months. The costs included societal costs and private costs, including the time patients spent in treatment. Results are presented as incremental cost-effectiveness ratio (ICER). The total costs per patient were significantly lower for DL-PDT (€132) compared with LED-PDT (€170), giving a cost saving of €38 (p = 0.022). The estimated probabilities for patients' complete response were 0.429 for DL-PDT and 0.686 for LED-PDT; a difference in probability of being healed of 0.257. ICER showed a monetary gain of €147 per unit of effectiveness lost. DL-PDT is less costly and less effective than LED-PDT. In terms of cost-effectiveness analysis, DL-PDT provides lower value for money compared with LED-PDT.

[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.

Italian guidelines and therapeutic algorithm for actinic keratoses.

The prevalence of actinic keratosis (AK) continues to rise among white people throughout the world and it is necessary to increase the level of attention paid to it from a diagnostic and a preventive point of view. Today, AK must be considered an in situ squamous cell carcinoma and as such, must be managed using one of the available approved therapeutic alternatives. However, when multiple AKs develop on severely photodamaged skin, the treatment of the lesion together with that of the field of cancerization is part of an optimal strategy that aims not only to solve alterations clinically evident but also those in the surrounding skin field cancerization, that most likely hosts genetic alterations and is the site of initial gradual replacement of normal cells with tumoral cells. This paper reports the most recent evidences from a careful review of the literature's key articles of the treatment of AKs and suggests guidelines for the clinicians. The guidelines indicated by the authors have also been based on practical evaluations and their own clinical experience. The present conclusions may be modified by new findings in the field of oncologic research.