Photodynamische Therapie (PDT) und wassergefiltertes Infrarot A (wIRA) bei Patienten mit therapierefraktären vulgären Hand- und Fußwarzen

Background: Common warts (verrucae vulgares) are human papilloma virus (HPV) infections with a high incidence and prevalence, most often affecting hands and feet, being able to impair quality of life. About 30 different therapeutic regimens described in literature reveal a lack of a single striking strategy. Recent publications showed positive results of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) in the treatment of HPV-induced skin diseases, especially warts, using visible light (VIS) to stimulate an absorption band of endogenously formed protoporphyrin IX. Additional experiences adding waterfiltered infrared A (wIRA) during 5-ALA-PDT revealed positive effects. Aim of the study: First prospective randomised controlled blind study including PDT and wIRA in the treatment of recalcitrant common hand and foot warts. Comparison of "5-ALA cream (ALA) vs. placebo cream (PLC)" and "irradiation with visible light and wIRA (VIS+wIRA) vs. irradiation with visible light alone (VIS)". Methods: Pre-treatment with keratolysis (salicylic acid) and curettage. PDT treatment: topical application of 5-ALA (Medac) in "unguentum emulsificans aquosum" vs. placebo; irradiation: combination of VIS and a large amount of wIRA (Hydrosun® radiator type 501, 4 mm water cuvette, waterfiltered spectrum 590-1400 nm, contact-free, typically painless) vs. VIS alone. Post-treatment with retinoic acid ointment. One to three therapy cycles every 3 weeks. Main variable of interest: "Percent change of total wart area of each patient over the time" (18 weeks). Global judgement by patient and by physician and subjective rating of feeling/pain (visual analogue scales). 80 patients with therapy-resistant common hand and foot warts were assigned randomly into one of the four therapy groups with comparable numbers of warts at comparable sites in all groups. Results: The individual total wart area decreased during 18 weeks in group 1 (ALA+VIS+wIRA) and in group 2 (PLC+VIS+wIRA) significantly more than in both groups without wIRA (group 3 (ALA+VIS) and 4 (PLC+VIS)): medians and interquartile ranges: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). After 18 weeks the two groups with wIRA differed remarkably from the two groups without wIRA: 42% vs. 7% completely cured patients; 72% vs. 34% vanished warts. Global judgement by patient and by physician and subjective rating of feeling was much better in the two groups with wIRA than in the two groups without wIRA. Conclusions: The above described complete treatment scheme of hand and foot warts (keratolysis, curettage, PDT treatment, irradiation with VIS+wIRA, retinoic acid ointment; three therapy cycles every 3 weeks) proved to be effective. Within this treatment scheme wIRA as non-invasive and painless treatment modality revealed to be an important, effective factor, while photodynamic therapy with 5-ALA in the described form did not contribute recognisably - neither alone (without wIRA) nor in combination with wIRA - to a clinical improvement. For future treatment of warts an even improved scheme is proposed: one treatment cycle (keratolysis, curettage, wIRA, without PDT) once a week for six to nine weeks. © 2004 Fuchs et al; licensee German Medical Science. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL : http://www.egms.de/en/gms/volume2.shtmlHintergrund: Vulgäre Warzen (Verrucae vulgares) sind humane Papillomvirus-Infektionen (HPV) mit einer hohen Inzidenz und Prävalenz, die am häufigsten Hände und Füße befallen und die in der Lage sind, die Lebensqualität zu beeinträchtigen. Etwa 30 in der Literatur beschriebene Therapieverfahren zeugen von einem Mangel an einer einzigen überzeugenden Strategie. Jüngste Veröffentlichungen zeigten positive Ergebnisse der Photodynamischen Therapie (PDT) mit 5-Aminolävulinsäure (5-ALA) in der Therapie von HPV-induzierten Hautkrankheiten, besonders Warzen, wobei sichtbares Licht (VIS) verwendet wird, um ein Absorptionsband des endogen aus 5-ALA gebildeten Protoporphyrin IX zu stimulieren. Weitere Erfahrungen, wassergefiltertes Infrarot A (wIRA) während der 5-ALA-PDT zusätzlich anzuwenden, offenbarten positive Wirkungen. Ziel der Untersuchung: Erste prospektive randomisierte kontrollierte Blind-Studie, die PDT und wIRA in die Behandlung von therapierefraktären vulgären Hand- und Fußwarzen einbezieht. Vergleich von "5-ALA-Salbe (ALA) vs. Placebo-Salbe (PLC)" und "Bestrahlung mit sichtbarem Licht und wIRA (VIS+wIRA) vs. Bestrahlung mit sichtbarem Licht allein (VIS)". Methoden: Vorbehandlung mit Keratolyse (Salizylsäure) und Kürettage. Photodynamische Therapie (PDT): topische Applikation von 5-ALA (Medac) in "Unguentum emulsificans aquosum" vs. Placebo; Bestrahlung: Kombination von sichtbarem Licht (VIS) und einem hohen Maß an wassergefiltertem Infrarot A (wIRA) (Hydrosun®-Strahler Typ 501, 4 mm Wasserküvette, wassergefiltertes Spektrum 590-1400 nm, kontaktfrei, typischerweise schmerzlos) vs. sichtbares Licht (VIS) allein. Nachbehandlung mit Vitamin-A-Säure-Salbe. Ein bis drei Therapiezyklen im Abstand von 3 Wochen. Hauptzielvariable: "Prozentuale Änderung der Gesamtwarzenfläche jedes Patienten über die Zeit" (18 Wochen). Globales Urteil von Patient und von Arzt sowie subjektive Einschätzung von Empfindung/Schmerz (visuelle Analogskalen). 80 Patienten mit therapierefraktären vulgären Hand- und Fußwarzen wurden randomisiert einer der vier Behandlungsgruppen (mit vergleichbarer Anzahl an Warzen in vergleichbaren Lokalisationen in allen Gruppen) zugeteilt. Ergebnisse: Die individuelle Gesamtwarzenfläche nahm während 18 Wochen in Gruppe 1 (ALA+VIS+wIRA) und in Gruppe 2 (PLC+VIS+wIRA) signifikant mehr als in den beiden Gruppen ohne wIRA (Gruppe 3 (ALA+VIS) und 4 (PLC+VIS)) ab: Mediane und Interquartil-Spannen: -94% (-100%/-84%) vs. -99% (-100%/-71%) vs. -47% (-75%/0%) vs. -73% (-92%/-27%). Nach 18 Wochen unterschieden sich die zwei Gruppen mit wIRA deutlich von den zwei Gruppen ohne wIRA: 42% vs. 7% komplett geheilte Patienten; 72% vs. 34% völlig verschwundene Warzen. Das globale Urteil von Patient und von Arzt und die subjektive Einschätzung des Empfindens waren in den zwei Gruppen mit wIRA viel besser als in den zwei Gruppen ohne wIRA. Folgerungen: Das oben beschriebene vollständige Therapieschema von Hand- und Fußwarzen (Keratolyse, Kürettage, Photodynamische Therapie, Bestrahlung mit VIS+wIRA, Vitamin-A-Säure-Salbe; drei Therapiezyklen im Abstand von 3 Wochen) erwies sich als effektiv. Innerhalb des Therapieschemas zeigte sich wIRA - als nicht-invasive und schmerzlose Therapiemodalität - als ein wichtiger, effektiver Faktor, während die Photodynamische Therapie mit 5-ALA in der beschriebenen Form nicht erkennbar - weder alleine (ohne wIRA) noch in Kombination mit wIRA - zu einer klinischen Verbesserung beitrug. Für die zukünftige Behandlung von Warzen wird ein weiter verbessertes Schema vorgeschlagen: ein Therapiezyklus (Keratolyse, Kürettage, wIRA, ohne PDT) einmal pro Woche für sechs bis neun Wochen

Generation of Free Fatty Acids from Phospholipids Regulates Stratum Corneum Acidification and Integrity

There is evidence that the “acid mantle” of the stratum corneum is important for both permeability barrier formation and cutaneous antimicrobial defense. The origin of the acidic pH of the stratum corneum remains conjectural, however. Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed. We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to stratum corneum acidification and function. Topical applications of two chemically unrelated secretory phospholipase sPLA2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered stratum corneum integrity (number of strippings required to break the barrier) and decreased stratum corneum cohesion (protein weight removed per stripping). Not only stratum corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors. Moreover, exposure of intact murine stratum corneum to a neutral pH for as little as 3 h produced comparable abnormalities in stratum corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations. Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in stratum corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels. Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the stratum corneum (shown by immunofluorescence staining and vizualized by confocal microscopy). Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal stratum corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of stratum corneum integrity and cohesion

Activity of different desoximetasone preparations compared to other topical corticosteroids in the vasoconstriction assay

Introduction: We report on a double-blind, vehicle-controlled, single-center confirmatory study with random assignment. The purpose of the study was to investigate the topical bioavailability of different topical corticosteroid formulations in healthy human beings focussing on desoximetasone (DM). Materials and Methods: Two DM 0.25% formulations {[}ointment (DM-o) and fatty ointment (DM-fo, water-free); class III corticosteroids], the corresponding active ingredient-free vehicles and three comparators of different strength {[}clobetasol propionate 0.05% (CP 0.05%), fatty ointment, class IV; hydrocortisone (HC) 1%, fatty ointment, class I, and betamethasone (BM) 0.05%, fatty ointment, class III] were tested using the vasoconstriction assay. The degree of vasoconstriction (blanching) in the treatment field was compared to the one found in untreated control fields using chromametric measurements and clinical assessment. Results/Conclusion: DM-o 0.25%, DM-fo 0.25% and BM 0.05% showed similar vasoconstrictive potential, i.e., clear blanching. In fact, both DM preparations were proven to be non-inferior to BM 0.05%, while CP 0.05% was found a little less active. HC 1.0% and the DM vehicles showed no clear-cut vasoconstrictive effect. No adverse events related to the study medications were observed. Good topical bioavailability of both DM formulations was detected by chromametric measurement and clinical assessment. Copyright (C) 2008 S. Karger AG, Basel

Topical Peroxisome Proliferator Activated Receptor Activators Accelerate Postnatal Stratum Corneum Acidification

Previous studies have shown that pH declines from between 6 and 7 at birth to adult levels (pH 5.0–5.5) over 5–6 days in neonatal rat stratum corneum (SC). As a result, at birth, neonatal epidermis displays decreased permeability barrier homeostasis and SC integrity, improving days 5–6. We determined here whether peroxisome proliferator-activated receptor (PPAR) activators accelerate postnatal SC acidification. Topical treatment with two different PPARα activators, clofibrate and WY14643, accelerated the postnatal decline in SC surface pH, whereas treatment with PPARγ activators did not and a PPARβ/δ activator had only a modest effect. Treatment with clofibrate significantly accelerated normalization of barrier function. The morphological basis for the improvement in barrier function in PPARα-treated animals includes accelerated secretion of lamellar bodies and enhanced, postsecretory processing of secreted lamellar body contents into mature lamellar membranes. Activity of β-glucocerebrosidase increased after PPARα-activator treatment. PPARα activator also improved SC integrity, which correlated with an increase in corneodesmosome density and increased desmoglein-1 content, with a decline in serine protease activity. Topical treatment of newborn animals with a PPARα activator increased secretory phospholipase A2 activity, which likely accounts for accelerated SC acidification. Thus, PPARα activators accelerate neonatal SC acidification, in parallel with improved permeability homeostasis and SC integrity/cohesion. Hence, PPARα activators might be useful to prevent or treat certain common neonatal dermatoses

Impact of Age and Body Site on Adult Female Skin Surface pH

Background: pH is known as an important parameter in epidermal barrier function and homeostasis. Aim: The impact of age and body site on skin surface pH (pH(SS)) of women was evaluated in vivo. Methods: Time domain dual lifetime referencing with luminescent sensor foils was used for pH(SS) measurements. pH(SS) was measured on the forehead, the temple, and the volar forearm of adult females (n = 97, 52.87 +/- 18.58 years, 20-97 years). Every single measurement contained 2,500 pH values due to the luminescence imaging technique used. Results: pH(SS) slightly increases with age on all three investigated body sites. There are no significant differences in pH(SS) between the three investigated body sites. Conclusion: Adult pH(SS) on the forehead, the temple and the volar forearm increases slightly with age. This knowledge is crucial for adapting medical skin care products. Copyright (C) 2012 S. Karger AG, Base

Glycerol accelerates recovery of barrier function in vivo.

Two studies were performed to evaluate the influence of glycerolon the recovery of damaged stratum corneum barrier function.Measurements of transepidermal water loss and capacitancewere conducted in a 3-day follow-up after tape stripping (study1) and a 7-day follow-up after a barrier damage due to arepeated washing with sodium lauryl sulphate. In study 1 afaster barrier repair (transepidermal water loss) was monitoredin glycerol-treated sites. Significant differences between glycerolopen vs. untreated and glycerol occluded vs. untreated wereobserved at day 3. Stratum corneum hydration showedsignificantly higher values in the sites treated with glycer-olzocclusion, compared with all other sites. In study 2 a fasterbarrier repair was seen in glycerol-treated sites, with significantdifferences against untreated and base-treated sites 7 days afterthe end of the treatment. Stratum corneum hydration showedhighest values in the glycerol treated sites after 3 days oftreatment. Glycerol creates a stimulus for barrier repair andimproves the stratum corneum hydration; stratum corneumhydration is not strictly related to barrier homeostasis and canbe optimized by different mechanisms and pathways. Theobserved effects were based on the modulation of barrier repairand were not biased by the humectant effect of glycerol. As theglycerol-induced recovery of barrier function and stratumcorneum hydration were observed even 7 days after the endof treatment, glycerol can be regarded as a barrier stabilizingand moisturizing compound. Key words: tape stripping; SLSwashing; transepidermal water loss (TEWL); capacitance;occlusion; barrier repair.(Accepted May 19, 1999.)Acta Derm Venereol 1999; 79: 418–421.Joachim Fluhr, Department of Dermatology, KarlsruheHospital, Sta¨dt. Klinikum, Moltkestrasse 120, D-76133Karlsruhe, Germany.The mechanisms promoting barrier repair in vivo afterstripping of the stratum corneum (SC) and repeated irritationwith sodium lauryl sulphate (SLS) are not completely clear:the modulation of water flux is probably a key factor involvedin barrier repair (1–7). It is known, that glycerol represents ahygroscopic compound capable of absorbing water from theenvironment and deeper parts of the SC.The purpose of the present study was to evaluate in vivothe effects of glycerol and occlusion in the promotion ofbarrier repair. Two studies were performed to evaluate theeffect of a repeated application of glycerol on damaged SCbarrier. The barrier disruption was performed by tapestripping (study 1) and by repeated washing with SLS over4 days (study 2).MATERIALS AND METHOD

Environmental Risk Factors for Chronic Pancreatitis and Pancreatic Cancer

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke

An Expert Position Paper from the Special Interest Group on Sensitive Skin of the International Forum for the Study of Itch

Sensitive skin is a frequent complaint in the general population, in patients, and among subjects suffering from itch. The International Forum for the Study of Itch (IFSI) decided to initiate a special interest group (SIG) on sensitive skin. Using the Delphi method, sensitive skin was defined as “A syndrome defined by the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) in response to stimuli that normally should not provoke such sensations. These unpleasant sensations cannot be explained by lesions attributable to any skin disease. The skin can appear normal or be accompanied by erythema. Sensitive skin can affect all body locations, especially the face”. This paper summarizes the background, unresolved aspects of sensitive skin and the process of developing this definition

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio