Efficacy and Safety of Secukinumab in Elderly Patients with Moderate to Severe Plaque-Type Psoriasis: Post-Hoc Analysis of the SUPREME Study.

Purpose: Secukinumab is a fully human monoclonal antibody that inhibits interleukin (IL)-17A approved for the treatment of moderate to severe plaque psoriasis in adults and children. We compared the efficacy and safety of secukinumab in patients aged < 65 years (adult patients) versus patients aged ≥ 65 years (elderly patients) in a post-hoc analysis of the SUPREME study. Patients and Methods: Patients with moderate to severe plaque psoriasis received subcutaneous secukinumab 300 mg per week for the first 5 weeks, then 300 mg per month. We compared the following outcomes in patients aged ≥ 65 years vs < 65 years: baseline characteristics; PASI50/75/90/100 response rates (improvements ≥ 50%/75%/90%/100% in Psoriasis Area and Severity Index (PASI) from baseline); changes in Dermatology Life Quality Index (DLQI); Hospital Anxiety and Depression Scale (HAD-A, HAD-D) score changes; treatment-emergent adverse events (TEAEs). Results: Secukinumab was slightly less effective in elderly patients than in adult patients (response rates at week 16: PASI90, 69.4% vs 80.9%, p = 0.4528; PASI100, 44.4% vs 56.7%, p = 0.8973). Elderly and adult patients showed a similar time course of changes in absolute PASI scores. Patients aged ≥ 65 years had a statistically significantly lower improvement in quality of life (mean DLQI reduction) than patients aged < 65 years at week 16 [-5.4 (±4.3) vs -8.8 (±6.9), p = 0.0065] and at week 24 [-5.3 (±4.4) vs -9.2 (±7.1), p = 0.0038]. Secukinumab treatment resulted in comparable mean reductions in anxiety and depression scores in both cohorts at 24 weeks [HAD-A, -1.3 (±3.3) vs -2.1 (±3.8), p = 0.9004; HAD-D, -1.0 (±3.3) vs -1.5 (±3.1), p = 0.4598]. The frequency of TEAEs in the two cohorts was similar (16.7% vs 14.6%, p = 0.7391). Conclusion: Secukinumab is a valid option for the management of moderate to severe psoriasis in elderly patients.

Cryotherapy for Actinic Keratosis: Basic Principles and Literature Review.

Actinic keratoses (AKs) are pre-malignant epithelial lesions induced by chronic cumulative UV exposure. Several guidelines concerning AKs treatment have been published in the past years. Among destructive procedures, cryotherapy is today considered a standard first-line approach in case of single lesions. The aim of the present review article is to analyse the treatment technique, its efficacy and safety.

Ultrapulsed CO2 Resurfacing of Photodamaged Facial Skin in Vegan and Omnivore Patients: A Multicentric Study.

BACKGROUND AND OBJECTIVES: Skin photoaging is related to extrinsic environmental exposures, mainly represented by ultraviolet radiation. One of the treatment options is laser resurfacing. As nutritional status is involved in cutaneous photodamage, we evaluated whether dietary patterns can also influence the response to facial resurfacing. Our prospective multicentric study involves three dermatologic centers specialized in laser therapy in northern Italy. The study aims to compare the outcome of a CO2 ablative laser therapy between omnivore and vegan patients. STUDY DESIGN/MATERIALS AND METHODS: Fifty-three omnivore and fifty-three vegan women undergoing ultrapulsed CO2 resurfacing for photodamaged facial skin were enrolled in this study. Clinical improvement was evaluated 3 and 6 months after the treatment using the modified Dover score. RESULTS: After laser treatment, vegans showed slower complete re-epithelialization (P < 0.001*) and disappearance of the erythema (P < 0.001*). After 3 and 6 months, vegans showed worse outcomes in terms of fine lines (P < 0.001* and P < 0.001*, respectively) and tactile roughness (P = 0.003* and ​​​​P = 0.002*, respectively) compared with omnivores, while they did not differ in mottled pigmentation. CONCLUSIONS: The present study suggests that diet influences the clinical outcome of fractioned CO2 laser treatment. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Cold Atmospheric Plasma (CAP) for the Treatment of Actinic Keratosis and Skin Field Cancerization: Clinical and High-Frequency Ultrasound Evaluation.

INTRODUCTION: Cold atmospheric plasma (CAP) has been clinically demonstrated to be an effective treatment for actinic keratosis (AK) in a number of case series. In this study, we evaluated the efficacy of CAP in the treatment of multiple AKs and assessed morphological changes induced on the skin field of cancerization both clinically and by high-frequency ultrasound (HFUS). METHODS: Patients with multiple grade I-II AKs of the scalp and/or face who were resistant or intolerant to conventional field-directed treatments were enrolled. CAP treatments were performed using a microwave-driven argon plasma jet. At baseline and 3 months after the last CAP session, performance indexes were determined using three-dimensional digital pictures and HFUS investigations were performed on a representative Olsen grade II AK and a small spot of clinically unaffected skin within the test area. RESULTS: Twelve patients were enrolled in the study. All clinical variables showed a statistically significant reduction after CAP. HFUS evaluation revealed that the total, epidermal and dermal thicknesses of the target AKs had not changed with treatment. CAP therapy significantly increased dermal density in both the target AK and the surrounding photodamaged skin and signficantly decreased the thickness of the subepidermal low-echogenic band in the perilesional skin, which is an ultrasound sign of photodamage. CONCLUSIONS: Cold atmospheric plasma was found to be an effective treatment for patients with multiple AKs. CAP was not followed by skin atrophy. HFUS examiniation showed the CAP improved features of chronic photodamage of the dermis of the skin underlying and surrounding the AK spots.

Photodynamic therapy for actinic keratosis in vegan and omnivore patients: the role of diet on skin healing.

Background: Photodynamic therapy (PDT) is an approved and effective treatment for actinic keratosis (AK). The time of complete skin healing is estimated to range between 5 and 10 days, but the role of nutrition in influencing it has never been evaluated.Objective: The aim of this study was to compare the time of skin healing and side effects in omnivores and vegans treated with PDT for AK.Materials and methods: Thirty omnivore and thirty vegan patients, treated with PDT for AK, were enrolled. Side effects, according to local skin response (LSR) score, were compared after 3, 7, and 30 days; the time of complete skin healing was recorded.Results: At day 3, day 7, and day 30 post treatment, vegan group showed higher total LSR score (p = .008, p < .001, p < .001, respectively), highlighting higher edema and vesiculation at day 3 (p < .001, p = .002, respectively), erythema, desquamation, edema, and vesiculation at day 7 (p < .001, p < .001, p < .001, p < .001, respectively) and erythema and desquamation after 30 days (p < .001, p < .001, respectively). The difference of complete skin healing was statistically significant (p < .001).Conclusions: The present study suggests that diet may have a prognostic and predictive role on PDT outcomes in term of side effects and time of skin repair.

Italian expert consensus paper on the management of patients with actinic keratoses.

Two round tables involving experts were organized in order to reach a consensus on the management of patients with actinic keratosis (AK). In the first, seven clinical questions were selected and analyzed by a systematic literature review, using a Population, Intervention, Control, and Outcomes framework; in the second, the experts discussed relevant evidences and a consensus statement for each question was developed. Consensus was reached among experts on how to best treat AK patients with respect to different clinical scenarios and special populations. Lesion-directed treatments are preferred in patients with few AKs. Patients with multiple AKs are challenging, with more than one treatment usually needed to achieve complete lesion clearance or a high lesion response rate, therapy should be personalized, based on previous treatments, patient, and lesion characteristics. Methyl aminolevulinate-PDT, DL (day light) PDT, and imiquimod cream were demonstrated to have the lowest percentage of new AKs after post treatment follow-up. For IMQ 5% and 3.75%, a higher intensity of skin reactions is associated with higher efficacy. Photodynamic therapy (PDT) is the most studied treatment for AKs on the arms. Regular sunscreen use helps preventing new AKs. Oral nicotinamide 500 mg twice daily, systemic retinoids and regular sunscreen use were demonstrated to reduce the number of new squamous cell carcinomas in patients with AKs. Limited evidence is available for the treatment of AKs in organ transplant recipients. There is no evidence in favor or against the use of any of the available treatments in patients suffering from hematological cancer.

Pediatric dermatologic surgery: our experience.

BACKGROUND: Surgical treatment for pediatric skin disorders is used for diagnostic and therapeutic reasons. We underline these procedures are usually easy and uncomplicated without the need for general anesthesia. Objective of this study was to share our experience in the field of pediatric dermatologic surgery. METHODS: We retrospectively analysed records of all pediatric patients receiving surgical therapy at the Dermatology Department of Spedali Civili of Brescia. Demographic data and treatments characteristics were recorded and analyzed. RESULTS: During the study period of one year, 670 surgical treatments concerning pediatric patients were collected. Number of procedures progressively grows with increasing age. All treatments were performed under local anesthesia except for a dermatofibrosarcoma protuberans for which general anesthesia was needed. CONCLUSIONS: Our data show that cryosurgery, electrodessication and excisional surgery constitute with equal proportion almost the whole of surgical procedures in dermatologic pediatric patients. Dermatologist's habit to perform surgery in local anesthesia avoids the risk of overtreatments, limits discomfort, anxiety, and pain perception linked to procedures performed.

Sun Exposure and Melanoma, Certainties and Weaknesses of the Present Knowledge.

Sun exposure is the main risk factor for cutaneous malignant melanoma (CMM). However, the UV-related pathogenetic mechanisms leading to CMM are far to be fully elucidated. In this paper we will focus on what we still don't fully know about the relationship between UVR and CMM. In particular, we will discuss: the action spectrum of human CMM, how different modalities of exposure (continuous/ intermittent; erythemal/ suberythemal) relate to different CMM variants, the preferential UVR induced DNA mutations observed in different CMM variants, the role of UV-related and UV-unrelated genetic damages in the same melanoma cells. Moreover, we will debate the importance of UVA induced oxidative and anaerobic damages to DNA and other cell structures and the role of melanins, of modulation of innate and acquired immunity, of vitamin D and of chronic exposure to phototoxic drugs and other xenobiotics. A better understanding of these issues will help developing more effective preventative strategies and new therapeutic approaches.

Prevalence of Phototherapy in the Age of Biologics.

BACKGROUND: The prevalence of narrow-band ultraviolet B (NB-UVB) use in Europe for moderate and severe psoriasis is unknown, because national registries for psoriasis do not monitor this treatment. OBJECTIVES: To quantify the use of phototherapy, biologics or conventional treatments in psoriasis, in a setting where European Medicines Agency (EMA) eligibility criteria for biologics were strictly applied, and phototherapy was included among first-line treatments. METHODS: We followed a cohort of 1,090 patients who were referred to the only centre entitled to prescribe biologics and phototherapy during a 5-year period. RESULTS: The cumulative number of treatment cycles was: 1,047 with NB-UVB phototherapy, 650 with systemic treatments and 239 with biologics; 754 patients received at least 1 course of NB-UVB phototherapy, 422 at least 1 course with a systemic treatment and 137 with a biologic; 595 patients were treated only with phototherapy. CONCLUSIONS: Regular use of NB-UVB as first-line treatment for moderate and severe psoriasis and adherence to the EMA eligibility criteria for biologics led to a relatively restricted use of biologics.

Evaluation of the costs of topical treatments for actinic keratosis based on lesion response and the affected area.

BACKGROUND: The cost of topical treatments for actinic keratosis (AK) has never been evaluated with respect to the actual cancerization field treated and the corresponding lesion response rate. Traditionally, evaluation in AK has been done in the context of patient response rate alone. The current study aimed to develop an economic model assessing the cost of topical treatments for the management of AK in Italy. METHODS: Data from Italian patients (N.=100) with five or more mild/moderate lesions on the face and/or scalp was used. The efficacy of the topical treatments which are available for the treatment of AK in Italy was considered. The outcome of interest was lesion response rates at three months and was based on published literature. The cost of each treatment was estimated according to the approval status of the drug and the cancerization area that required treatment. The analysis was replicated for four other European countries. RESULTS: The average costs of treatment with c-PDT, DL PDT, DHA, InMeb and IMQ were € 364.2, € 255.5, € 848.7, € 1039.1, and € 628.3, respectively. Taking into account the number of lesions cleared per patient, the cancerization area treated, and the number of visits required with each treatment, the total costs per lesion treated per patient were estimated at € 37.9, € 29, € 264.7, € 103.5, and € 115.4, respectively. The analysis produced consistent results when it was replicated for other countries. CONCLUSIONS: Daylight therapy with methyl aminolevulinate (DL PDT) is an effective treatment option for AK management with a favourable value for money profile.

Pulsed CO2 Laser Ablation of Superficial Basal Cell of Limbs and Trunk: A Comparative Randomized Clinical Trial With Cryotherapy and Surgical Ablation.

BACKGROUND: Pulsed CO2 laser is a treatment of superficial basal cell carcinoma (sBCC) although robust clinical evidence has not been reported so far. OBJECTIVE: The authors investigated efficacy, safety, time to wound healing, cosmetic outcome, patient satisfaction, and cost-effectiveness ratio of pulsed CO2 laser in comparison to cryotherapy and surgery. MATERIALS AND METHODS: BCCs of the trunk and extremities were randomized to one of the treatments. After 90 days, efficacy and cosmetic outcome were assessed. Patients recorded the time to complete healing of the wound and scored their overall satisfaction. RESULTS: Two hundred forty patients were randomized. After 3 months, complete remission (CR) rate with pulsed CO2 laser was 78.8%. This was significantly lower than surgery, whereas the CR rate with cryotherapy was not significantly different. Cosmetic result was better with surgery. High satisfaction was reported by 65.0% of patients treated with CO2 ablation. Time of wound healing was significantly shorter with CO2 laser. CONCLUSION: In comparison to cryotherapy, pulsed CO2 laser showed no statistically significant difference in efficacy, cosmetic outcome, and patient satisfaction. Time to healing was shorter; the cost and cost-effectiveness ratio were similar. Surgery had the greatest efficacy rate. The main limitation of this study was the short duration of follow-up (3 months).

A Randomized Split-Face Clinical Trial of Photodynamic Therapy with Methyl Aminolevulinate versus Ingenol Mebutate Gel for the Treatment of Multiple Actinic Keratoses of the Face and Scalp.

BACKGROUND: Photodynamic therapy with methyl aminolevulinate (MAL-PDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs). OBJECTIVE: The aim of this intraindividual, split-face, randomized clinical trial was to compare treatment outcomes of MAL-PDT and IMB. METHODS: Two symmetrical contralateral areas with a similar number of AKs were selected and randomly assigned to 3 days of an IMB treatment cycle or a single session of MAL-PDT. The next day, the local skin reaction (LSR) score was registered. The patients scored pain and time to healing of the treatment area. RESULTS: After 90 days, the complete remission rate of lesions, the number of patients with complete remission of all lesions, cosmetic outcome, and patient preference were assessed. CONCLUSION: According to our results, IMB and MAL-PDT had a similar efficacy, but the cosmetic outcome was superior with MAL-PDT. Pain was higher with PDT, but LSR was more severe and time to healing was longer with IMB. Patients preferred MAL-PDT.

A randomized split-face clinical trial analyzing daylight photodynamic therapy with methyl aminolaevulinate vs ingenol mebutate gel for the treatment of multiple actinic keratoses of the face and the scalp.

INTRODUCTION: Daylight photodynamic therapy with methyl aminolaevulinate (dlPDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs). The aim of this comparative, intra-patient, split-face, randomized clinical trial was to compare treatment outcomes of dlPDT and IMB. METHODS: Two symmetrical contralateral areas of 25cm2, harboring a similar (5-10) number of AKs, were selected and randomly assigned either to a 3days' IMB treatment cycle or to a single session of dlPDT. The day after the local skin reaction (LSR) score was registered. Patients' scored pain (assessed through VAS method) after the treatment, and time needed for wound closure, were subsequently registered. After 90days, the complete remission (CR) rate recorded for both single lesions and patients, the cosmetic outcome and the patients' preference, were assessed. RESULTS: 22 patients with a total of 311 AKs were enrolled. The mean pain VAS score was 3.55±1.82 with IMB and 2.05±0.72 with dlPDT (p<0.01). The mean LSR score was 9.91±4.24 and 4.59±4.03 (p<0.01), respectively. The mean days necessary for wound closure were 9.45±3.51 and 4.36±1.18days (p<0.01), respectively. After 3 months, 119 lesions with IMB and 120 lesions with dlPDT were healed and the CR rate with IMB (75.8%) was non-inferior to the CR rate with dlPDT (77.9%). The comparisons of CR rates of grade I and II AKs did not show any inferiority for one treatment compared to the other. Eight patients (36.4%) had all lesions cleared with IMB and 7 (31.8%) with dlPDT (p=NS). The cosmetic outcome was better with dlPDT and 17 patients evaluated dlPDT as their preferred treatment. CONCLUSIONS: A 3days' treatment cycle with IMB and a single session of dlPDT had a similar efficacy for both grade I AKs and grade II AKs but dl PDT showed lower pain and inflammation scores, quicker wound closure, better cosmetic outcome and higher patients' preference.

Bucher's indirect comparison of daylight photodynamic therapy with methyl aminolevulinate cream versus diclofenac plus hyaluronic acid gel for the treatment of multiple actinic keratosis.

Actinic keratosis (AK) is a pre-cancerous condition characterised by patches of thick, scaly skin developing on sun-exposed areas of the body. When multiple AKs develop on severely photodamaged skin, commonly used treatments include photodynamic therapy and diclofenac plus hyaluronic acid gel (DHA). Methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) is an alternative to conventional photodynamic therapy (MAL c-PDT). Trials have indicated that MAL DL-PDT is as effective as MAL c-PDT but reduces treatment-related pain and dermatological side effects. To indirectly compare between MAL DL-PDT and DHA in patients with AK. A total of three randomised trials were collected using a systematic literature review. An adjusted indirect comparison was conducted on complete lesion response rate at 12 weeks. The data indicated that mild lesions, moderate lesions, and mild and moderate lesions treated with MAL DL-PDT were more than four times more likely to undergo a complete response than lesions treated with DHA at 12 weeks, with ORs ranging from 4.23 to 4.81. Results were all statistically significant. This is the first indirect comparison demonstrating the effectiveness of MAL-PDT over DHA for the treatment of AK, and further research is needed to assess the long-term efficacy of these interventions (i.e. six months and beyond), as well as safety and patient-reported outcomes.

Carcinoma Cuniculatum of the Foot Invading the Bone Mimicking a Pseudo-Epitheliomatous Reaction to an Acute Osteomyelitis.

Carcinoma cuniculatum is a rare variant of squamous cell carcinoma. The clinical presentation is usually a non-verrucous exophytic plaque or tumor of the plantar region with a penetration in the deep tissues. Histological examination shows a proliferation of well-differentiated keratinocytes. We describe a patient affected by a slowly enlarging tumoral lesion overlying the fifth metatarsum of the left foot. Clinical examination and radiological investigations suggested a chronic osteomyelitis and a first histological examination of a punch biopsy was suggestive of a pseudo-epitheliomatous hyperplasia. The patient underwent several cycles with systemic antibiotics without improvement. Finally, the fifth metatarso was amputated and the skin lesion was completely removed. The histological examination of the whole operatory mass allowed a diagnosis of carcinoma cuniculatum invading the bone.

Variables affecting clinical response to treatment of facial port-wine stains by flash lamp-pumped pulsed dye laser: the importance of looking beyond the skin.

The response of port-wine stains (PWS) to conventional laser treatment in adults is difficult to predict. To assess the influence of local or systemic hemodynamic variables on the clearance of PWS by using flash lamp-pumped pulsed (FLPP) dye laser. All consecutive patients ages 18 years or older undergoing laser treatment for a facial PWS were eligible. Laser sessions were scheduled every 8 weeks. All patients were evaluated based on a standard scale with four evaluation categories, from no or minimal improvement to total or almost total clearance. Clearance was achieved by 50.1 % (95 % confidence interval 35.6-64.7) of patients after a maximum of 15 treatment sessions. In multivariate analysis, increased age, a newly described Type III capillaroscopic pattern, and presence of lesions in dermatome V2 were all associated with a reduced clinical response to treatment. In a model restricted to demographic pattern and patient characteristics, arterial hypertension was also associated with a lower clinical response. A strong association was found between arterial hypertension and the Type III capillaroscopic pattern. Age, arterial hypertension, capillaroscopic pattern, and body location should be considered when planning laser treatment of PWS.

Detection and management of latent tuberculosis infections before biologic therapy for psoriasis.

The biologic agents can be highly efficacious in the treatment of psoriasis and psoriatic arthritis; however, their use is associated with an increased risk of developing active TB. In particular, TNF-α plays critical role in preventing TB infection and reactivation of latent TB infection (LTBI). Therefore, it is critical that all patients be screened for LTBI prior to initiating therapy. An expert panel of Italian dermatologists met recently with the goal of producing a consensus paper on screening and chemoprophylaxis for LTBI in Italian psoriasis patients treated with biologics. Current recommendations for the screening algorithm include medical history, chest x-ray, and tests that evaluate immunologic response to the presence of Mycobacterium tuberculosis. Patients with positive screening results and without active disease are to be treated with a full course of chemoprophylaxis; however, if the patient is compliant and tolerating the regimen, biologic therapy for psoriasis may be started after at least 1 month on prophylactic therapy when prompt control of disease is required.

Narrowband ultraviolet B phototherapy is a suitable treatment option for solar urticaria.

BACKGROUND: Narrowband (NB) ultraviolet (UV) B lamps are widely used for treatment and prophylaxis of several skin diseases. OBJECTIVE: We sought to assess the efficacy of two protocols of NB-UVB therapy for the prophylaxis of UVB-sensitive and UVB-insensitive solar urticaria (SU). METHODS: Subjects affected by SU underwent phototesting for assessment of the minimal erythemal dose and minimal urticarial dose. Patients without urticarial response to UVB underwent a single daily exposure every other day for 4 weeks (group A). Patients with a urticarial test response to broadband UVB or NB-UVB (group B) received 3 daily exposures (on working days) for the first week. Afterward, they were treated as the patients of group A for 3 weeks. Follow-up visits took place after 1 and 3 months. RESULTS: A total of 39 patients completed the study. In groups A (29 patients) and B (10 patients), the median total number of exposures was 12 (interquartile range [IQR]: 12; 15) and 25.5 (IQR 24; 27), respectively. The median total NB-UVB dose was 10.3 J/cm(2) (IQR 9.9; 11) for group A and 9.1 J/cm(2) (IQR 8.5; 10.6) for group B. At follow-up visits, patients reported good tolerance to the sun. LIMITATIONS: A direct comparison of NB-UVB with UVA or psoralen plus UVA for the photoprophylaxis of SU is still lacking. CONCLUSION: NB-UVB phototherapy was well-tolerated and effectively prevented SU relapses.

Cutaneous melanoma in patients in treatment with biological therapy: review of the literature and case report.

Herein we report a case of a melanoma arising in a patient receiving adalimumab and methotrexate for rheumatoid arthritis. A limited number of studies reported melanoma growth in patients undergoing treatment with biologics. This case report with a brief review of literature suggests that patients under treatment with biologics should be counseled to identify new pigmented lesions or changes in preexisting nevi. Clinicians' collaboration will facilitate recognition and timely diagnosis of early melanoma. If there is any doubt, excision for histological evaluation should be considered. Pending new studies, careful observation is encouraged.