Modern Approach to Topical Treatment of Aging Skin

The main processes involved in skin aging are intrinsic and extrinsic. Apart from them, so called stochastic aging connotes cell damage caused by metabolic processes, free radicals and cosmic irradiation. The clinical expression of intrinsic aging include smooth, dry, and thinned skin with accentuated expression lines. It is inevitable and time dependent. Extrinsically aged skin shows signs of photodamage which include appearance of wrinkles, pigmented lesions, actinic keratoses and patchy hypopigmentations. Therapeutic modalities imply photoprotection with sunscreens that prevent sunburns and block ultraviolet irradiation. Other modalities include use of retinoids which regulate gene transcription with subsequent cellular differentiation and proliferation. The topical and peroral administration of »network antioxidants» such as vitamin E and C, coenzyme Q10, alpha-lipoic acid and glutathione, enhance antiaging effect. The other antioxidants such as green tea, dehydroepiandrosterone, melatonin, selenium and resveratrol, have also antiaging and anti-inflammatory effects. Topical bleaching agents such as hydroquinone, kojic acid and azelaic acid can reduce signs of aging. Studies confirm the efficacy of these topical agents in combination with superficial and/or medium depth or deep peeling agents for photodamaged skin treatment. Indications for type of chemical peels according to various clinical diagnosis are done, as well as advantages and disadvantages of differetn types of chemical peels

Modern Approach to Topical Treatment of Aging Skin

The main processes involved in skin aging are intrinsic and extrinsic. Apart from them, so called stochastic aging connotes cell damage caused by metabolic processes, free radicals and cosmic irradiation. The clinical expression of intrinsic aging include smooth, dry, and thinned skin with accentuated expression lines. It is inevitable and time dependent. Extrinsically aged skin shows signs of photodamage which include appearance of wrinkles, pigmented lesions, actinic keratoses and patchy hypopigmentations. Therapeutic modalities imply photoprotection with sunscreens that prevent sunburns and block ultraviolet irradiation. Other modalities include use of retinoids which regulate gene transcription with subsequent cellular differentiation and proliferation. The topical and peroral administration of »network antioxidants» such as vitamin E and C, coenzyme Q10, alpha-lipoic acid and glutathione, enhance antiaging effect. The other antioxidants such as green tea, dehydroepiandrosterone, melatonin, selenium and resveratrol, have also antiaging and anti-inflammatory effects. Topical bleaching agents such as hydroquinone, kojic acid and azelaic acid can reduce signs of aging. Studies confirm the efficacy of these topical agents in combination with superficial and/or medium depth or deep peeling agents for photodamaged skin treatment. Indications for type of chemical peels according to various clinical diagnosis are done, as well as advantages and disadvantages of differetn types of chemical peels

Comparison of pulsed-dye laser-mediated photodynamic therapy and conventional photodynamic therapy in the treatment of multiple basal cell carcinomas

Bazocelularni karcinom je iznimno čest, spororastući, lokalno invazivni, maligni epidermalni tumor kože koji nastaje iz bazalnih keratinocita. Najzastupljeniji histološki podtipovi su nodularni i površinsko-šireći BCC. Zbog visoke učestalosti BCC-a važan cilj je pronalaženje optimalnog protokola liječenja, koji je jednak ili veći po učinkovitosti od dosada primijenjenih terapija, a da pri tome smanjuje nelagodnost bolesniku i potrebu za anestezijom te skraćuje vrijeme provedeno u zdravstvenoj ustanovi, posebno za bolesnike s višestrukim BCC-om. Fotodinamska terapija primjenjuje se u liječenju BCC-a niskog rizika. Pri tome se aktivira fotosenzibilizator, aminolevulinska kiselina vidljivom svjetlošću (nekoherentnim svjetlom) kako bi se proizveli reaktivni oblici kisika koji selektivno uništavaju stanice tumora. Bolovi koje bolesnik može osjećati tijekom fotodinamske terapije posljedica su nekroze, apoptoze stanica te posljedične upale. Koriste se razni izvori svjetlosti. Većina kliničkih ispitivanja je izvedena primjenom crvenog svjetla s valnim duljinama od oko 630 nm, što dopušta dublje prodiranje svjetla u kožu. No, definirani su i drugi niži vrhovi apsorpcije, pronađeni na 510, 545 i 580 nm. Pulsed-dye laser s koherentnim svjetlom valne duljine od 585 nm inducira blagu, ali primjetnu fotodinamičku reakciju. Budući da BCC sadržava krvne žile neposredno ispod epidermisa, veličine 0,2 mm ili šire, PDL se primjenjivao za liječenje BCC-a, ali kao vaskularni laser (principom selektivne fototermolize), bez fotosenzibilizatora. Fotodinamska terapija može biti dugotrajan terapijski postupak, osobito ako se izvodi u više navrata kao u bolesnika s višestrukim BCC-evima. Stoga bi bilo prikladnije tretirati višestruke niskorizične BCC-e fotodinamskom terapijom posredovanom PDL-om (PDL-PDT), jer to zahtijeva znatno manje vremena (ukupno 3 – 5 minuta). Pretpostavili smo da bi primjenom PDL-a sa specifičnim postavkama i u kombinaciji s fotosenzibilizatorom (ALA) postigli sinergistički učinak dva svojstva PDL-a: fotodinamski učinak te učinak selektivne fototermolize koje PDL ima kao vaskularni laser. Time bismo ostvarili učinkovitost usporedivu s učinkovitošću konvencionalnog PDT-a. U ovoj studiji usporedili smo jednokratan tretman PDL-PDT-om s konvencionalnim PDT-om u liječenju BCC-a u smislu učinkovitosti, kozmetskog učinka i razine boli u bolesnika s višestrukim BCC-ima. Studija je intraindividualna, odnosno dva terapijska modaliteta primjenjivala su se na različitim tumorima istog bolesnika. Istraživanje je bilo prospektivno, kontrolirano, intraindividualno i za istraživača zaslijepljeno. Provedeno je na 15 bolesnika sa 62 BCC-a. Višestruki tumori na pojedinačnom bolesniku podijeljeni su u dvije slične skupine i tretirani s kPDT-om (630 nm, nekoherentno LED svjetlo, intenzitetom od 30 mW/cm2 i ukupnom dozom od 150 J/cm2) i s 585 nm-PDLPDT- om (nastavkom od 7 mm, dozom od 10 J/cm2, trajanjem pulsa od 10 ms, s 10 % preklapanja i s tri prolaza uz hlađenje hladnim zrakom). Primarni ishod istraživanja je učinkovitost, odnosno potpuna regresija BCC-a u 3. i 12. mjesecu nakon intervencija. Sekundarni ishodi su usporedba razine boli tijekom PDL-PDT-a s boli tijekom kPDT-a te kozmetskog učinka (procjenjenog od zasljepljenog ispitivača) u 12. mjesecu nakon intervencija primijenjenih na istim bolesnicima s višestrukim BCC-ima (intraindividualna studija). Analiziran je i utjecaj veličine tumora te lokalizacije tumora na učinkovitost PDL-PDT-a i kPDT-a. Nije bilo značajnih razlika u terapijskom učinku između dva tretmana (P = 0,285). Potpuna regresija BCC-a nakon 3-mjesečnog praćenja vidjela se u 79 % BCC-a tretiranih kPDT-om i 74 % BCC-a tretiranih PDL-PDT-om. U 12. mjesecu potpuna regresija BCC-a tretiranih kPDT-om bila je 75 % (95 % CI 0,55-0,89) u usporedbi s 59 % (95 % CI 0,41-0,75) za područja tretirana PDL-PDT-om. Obje terapije pokazuju niske prosječne vrijednosti boli: 1,7 za kPDT i 2,6 za PDL-PDT (P = 0,049) te sličan kozmetski učinak (P = 0,763). Zaključno, jednokratno liječenje s tri prolaza PDL-PDT-om djelotvorno je u liječenju niskorizičnih BCC-a, ali je stopa recidiva viša nego u konvencionalnog PDT-a. PDL-PDT je povezan s niskom razinom boli, ima slične kozmetske prednosti kao kPDT, ali zahtijeva znatno kraće vrijeme liječenja te je prikladan za liječenje bolesnika s višestrukim BCC-ima.Conventional photodynamic therapy (kPDT) is used in the treatment of low risk basal cell carcinomas (BCC). Conventional PDT involves the activation of photosensitizer with visible red light to produce reactive oxygen species that selectively destroy the tumour cells. Pulsed Dye Laser (PDL) induces mild but noticeable photodynamic response. PDT can be a time-consuming procedure. Multiple low-risk BCCs could be treated with PDL as the source of light for PDT (PDL-PDT), as this requires significantly less time. In this prospective, controlled, intra-individual, investigator-blinded study we compared a single treatment of PDL-PDT with kPDT for BCCs in terms of efficacy, aesthetic outcome, and pain in patients with multiple BCCs. It was conducted on 15 patients with 62 BCCs. The BCCs on an individual patient were divided into two similarly-sized groups and treated with kPDT and PDL-PDT. Primary outcomes were complete BCC regression at months 3. and 12. Secondary outcomes were pain immediately after treatment, aesthetic outcome, evaluated by a blinded investigator and influence of tumor size and tumor localization on the efficacy of PDL-PDT and kPDT. The study showed that a single treatment with PDL-PDT is effective in clearing BCCs, but the recurrence rate is higher than in case of conventional PDT. PDL-PDT is associated with low treatment related pain and has similar cosmetic advantages

Apremilast Use in Severe Psoriasis: Real-World Data from Central and Eastern Europe

Introduction: The broad and sustained efficacy of apremilast for psoriasis has been demonstrated in randomized and real-world observational studies. Data from Central and Eastern Europe (CEE) are lacking. Moreover, apremilast use in this region is limited by country-specific reimbursement criteria. This is the first study to report data on the real-world use of apremilast in the region. Methods: APPRECIATE (NCT02740218) was an observational, retrospective, cross-sectional study assessing psoriasis patients 6 (± 1) months after apremilast treatment initiation. The study aimed to describe the characteristics of patients with psoriasis receiving apremilast, estimate treatment outcomes, including Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI), and assess dermatologists' and patients' perspectives on treatment using questionnaires including the Patient Benefit Index (PBI). Adverse event reports were taken from the medical records. Results: Fifty patients (Croatia: 25; Czech Republic: 20; Slovenia: 5) were enrolled. In patients continuing apremilast at 6 (± 1) months, mean (± SD) PASI score was reduced from 16.2 ± 8.7 points at treatment initiation to 3.1 ± 5.2 at 6 (± 1) months; BSA from 11.9% ± 10.3% to 0.8% ± 0.9%; DLQI from 13.7 ± 7.4 points to 1.6 ± 3.2. PASI 75 was reached by 81% of patients. Physicians reported that the overall treatment success fulfilled their expectations in more than two thirds of patients (68%). At least three-quarters of patients reported apremilast had a quite or very high benefit on the needs they identified as being most important. Apremilast was well tolerated; no serious or fatal adverse events were identified. Conclusion: Apremilast was effective in reducing skin involvement and improving quality of life in CEE patients having severe disease. Treatment satisfaction among physicians and patients was very high. These data add to the growing body of evidence showing consistent effectiveness of apremilast across the continuum of psoriasis disease severity and manifestations

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis

Abstract Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, setting, and participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main outcomes and measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients with Psoriasis

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.