Photodynamic therapy using intense pulsed light for treating actinic keratoses and photoaged skin of the dorsal hands: a randomized placebo-controlled study.

BACKGROUND: The efficacy of photodynamic therapy (PDT) with intense pulsed light (IPL) has been shown for treating actinic keratoses (AK) and improving photoaged skin on the face but not yet on the dorsal hands. OBJECTIVES: To evaluate the efficacy of PDT with IPL for treating AK of the dorsal hands, inducing neocollagenesis and improving photoaged skin. METHODS: In this prospective, randomized, placebo-controlled, monocentric, within-patient, observer-blinded trial, patients with one to four mild-to-moderate AK on the dorsal hands were randomly allocated to two different treatment groups: methyl aminolaevulinate (MAL) and IPL (λ ≥ 600 nm, 16·2 J cm-2 , three passes, Ellipse Flex PPT) (MAL-IPL) or placebo and IPL (λ ≥ 600 nm, 16·2 J cm-2 , three passes, Ellipse Flex PPT) (placebo-IPL). Patients received three treatments at 6-week intervals, and follow-up was 10 weeks after the last treatment. Thirty-seven patients aged 68·84 ± 9·28 years were randomized. The primary study end points were complete AK clearance per hand and neocollagenesis of subepidermal collagen 10 weeks after the last treatment. RESULTS: Ten weeks after the last treatment, complete AK clearance rates per hand were 54·5% after MAL-IPL and 3·0% after placebo-IPL (P < 0·0001); complete AK clearance rates per lesion were 69% and 15%, respectively (P < 0·001). The thickness of the subepidermal collagen band had increased by 290·6% (± 327·4%, P < 0·001) after MAL-IPL and by 215·5% (± 215·3%, P < 0·001) after placebo-IPL without any significant difference between the two groups. Ratings regarding mottled pigmentation and overall appearance by the blinded investigator were significantly higher for MAL-IPL than for placebo-IPL. Wrinkle size (MAL-IPL, -23·5%, P = 0·006; placebo-IPL, -17·7%, P = 0·010) and skin roughness (MAL-IPL, -18·3%, P < 0·001; placebo-IPL, -12·4%, P = 0·009) were significantly reduced in both groups without any significant difference between the two groups. CONCLUSIONS: On the dorsal hands, MAL-IPL reduced AK more efficaciously than placebo-IPL; both treatment modalities significantly improved photoaged skin.

Comparing cold-air analgesia, systemically administered analgesia and scalp nerve blocks for pain management during photodynamic therapy for actinic keratosis of the scalp presenting as field cancerization: a randomized controlled trial.

BACKGROUND: Photodynamic therapy (PDT) using methyl aminolaevulinate (MAL) is an effective treatment for extensive actinic keratosis (AK). However, pain is a major side-effect of this therapy. OBJECTIVES: To investigate whether scalp nerve blocks (group 1) provide adequate pain relief during MAL-PDT of the scalp and forehead in 32 men with baldness. METHODS: The patients received intravenous (IV) analgesia [piritramide 7.5 mg IV, plus oral metamizole (40 drops 30 min prior to PDT)] in combination with cold-air analgesia (group 2; IV analgesia) and cold-air analgesia alone (group 3). Maximum pain was evaluated by means of a visual analogue scale (VAS) during and up to 300 min after PDT. Pain during PDT was further analysed according to a pain perception scale. Furthermore, we measured haemodynamics and investigated stress hormone levels in blood samples at different time points. RESULTS: Maximum pain during PDT (primary end point) was significantly reduced in the treatment group receiving scalp nerve blocks (VAS 2.1 ± 1.3) compared with the treatment groups receiving IV analgesia (VAS 7.3 ± 1.1) and cold-air analgesia (VAS 8.4 ± 2.0; P < 0.05). No significant difference was found between groups 2 and 3 with regard to pain relief (P = 0.32). The increase in systolic blood pressure during the first 3 min of PDT was significantly lower for group 1 than for groups 2 and 3 (P < 0.001). No correlation between stress hormone levels and pain were found. CONCLUSIONS: Scalp nerve blocks provide an effective method for pain management during PDT for patients with extensive AK.

Fractional carbon dioxide laser resurfacing of rhytides and photoageing: a prospective study using profilometric analysis.

BACKGROUND: Results of profilometric skin analyses after fractional ablative skin resurfacing are not only important for evaluating the efficacy of this therapy but are also relevant for physicians practising laser and aesthetic skin therapy. Currently, objective measurements of wrinkle reduction after fractional CO2 laser resurfacing are scarce, and it remains unclear whether the various facial areas respond differently to this therapy. OBJECTIVES: To measure wrinkle parameters, the homogeneity of melanin distribution and skin roughness in four facial areas (periorbital, perioral, forehead, cheeks) before and after three fractional CO2 laser treatments. METHODS: Twenty-five women were analysed with regard to wrinkle parameters and mottled pigmentation on the face. We measured wrinkle size, depth and width and the homogeneity of melanin distribution and skin roughness in four facial areas before and after three fractional CO2 laser treatments. Additionally, the investigators rated clinical improvement using five-point grading scales. RESULTS: Wrinkles were significantly reduced in all facial areas, and the best results for wrinkle size and depth were found for the cheeks (-58·3%, P = 0·018 and -51·3%, P = 0·018) and the periorbital area (-35·1%, P < 0·001 and -31·1%, P = 0·001, respectively). The percentage improvements of rhytides evaluated by the investigators were mostly similar to those found from in vivo measurements. The homogeneity of melanin distribution in the skin was improved by 21·4% on the cheeks (P = 0·012) and by 24·0% in the periorbital area (P < 0·001). Clinical investigators rated the improvement of mottled pigmentation considerably higher (51-75%). CONCLUSIONS: After a serial treatment with the fractional CO2 laser, we measured considerably varying wrinkle reduction depending on the area of the face, and the best results were found for the cheeks.

Indocyanine green-augmented diode laser therapy vs. long-pulsed Nd:YAG (1064 nm) laser treatment of telangiectatic leg veins: a randomized controlled trial.

BACKGROUND: Telangiectatic leg veins (TLV) represent a common cosmetic problem. Near infrared lasers have been widely used in treatment because of their deeper penetration into the dermis, but with varying degrees of success, particularly because of different vessel diameters. Indocyanine green (ICG)-augmented diode laser treatment (ICG+DL) may present an alternative treatment option. OBJECTIVES: This trial evaluates the efficacy of ICG+DL in the treatment of TLV and compares the safety and efficacy of therapy with the standard treatment, the long-pulsed neodymium-doped yttrium aluminium garnet (Nd:YAG) laser. METHODS: In a prospective randomized controlled clinical trial, 29 study participants with TLV were treated with a Nd:YAG laser (λem = 1064 nm, 160-240 J cm(-2) , 65-ms pulse duration, 5-mm spot size) and ICG+DL (λem = 810 nm, 60-110 J cm(-2) , 48-87-ms pulse duration, 6-mm spot size; total ICG dose 4 mg kg(-1) ) in a side-by-side comparison in one single treatment setting that included histological examination in four participants. Two blinded investigators and the participants assessed clearance rate, cosmetic appearance and adverse events up to 3 months after treatment. RESULTS: According to both the investigators' and participants' assessment, clearance rates were significantly better after ICG+DL therapy than after Nd:YAG laser treatment (P < 0·05). On a 10-point scale indicating pain during treatment, participants rated ICG+DL therapy to be more painful (6·1 ± 2·0) than Nd:YAG laser (5·4 ± 2·0). CONCLUSIONS: ICG+DL therapy represents a new and promising treatment modality for TLV, with high clearance rates and a very good cosmetic outcome after one single treatment session.

Photoepilation with a diode laser vs. intense pulsed light: a randomized, intrapatient left-to-right trial.

BACKGROUND: Safe and efficient options for removing unwanted hair are in great demand. Laser devices and intense pulsed light (IPL) sources are the most commonly used treatment modalities. Yet, only a few randomized controlled trials (RCTs) comparing laser and IPL devices are available, and RCTs with long-term results are missing from the literature. OBJECTIVES: To compare the safety and long-term efficacy of diode lasers (DL) and IPL sources for axillary hair removal, we conducted an intrapatient, left-to-right, assessor-blinded and controlled trial. METHODS: IPL (Ellipse Flex PPT; Danish Dermatological Development, Hoersholm, Denmark; λem=600-950 nm) and DL (LightSheer XC system; Lumenis Inc., Santa Clara, CA, U.S.A.; λem=800 nm) treatments were evaluated in 30 study participants (skin type II-III) with unwanted axillary hair growth. Six treatments with each device were carried out at 4-week intervals. Final assessment was conducted 12 months after the last treatment by means of hair counts using close-up photographs. The primary endpoint was reduction in hair growth, analysed on an intention-to-treat and last-observation-carried-forward basis (n=30), and secondary endpoints were patient-rated efficacy, treatment-related pain, adverse effects and treatment duration. RESULTS: Both devices significantly reduced hair counts. Mean reductions from baseline (3 and 12 months after the last treatment) were 59·7% and 69·2% for DL and 42·4% and 52·7% for IPL treatment (P<0·01), respectively. DL treatment induced significantly more pain [3·7±2·1 (DL) vs. 1·6±1·4 (IPL); P<0·01; visual analogue scale] but could be conducted faster [33·1±3·8 s (DL) vs. 40·1±5·0 s (IPL); P<0·01]. No severe side-effects were observed for either therapy. CONCLUSIONS: Both DL and IPL treatments are highly effective, long lasting and safe. DL was found to be more effective than IPL treatment. DL treatment was more painful but less time-consuming than IPL therapy.

Intravenous injection of indocyanine green to enhance laser-assisted coagulation of blood vessels in skin - an animal study.

BACKGROUND: Laser therapy of vascular lesions, such as port wine stains (PWS) or leg veins are still imperfect due to different diameters and depth of vessels in tissue. We propose to improve blood vessel coagulation by intravenous introduction of an exogenous chromophore (indocyanine green, ICG) that effectively converts near-infrared (NIR) laser light into heat. OBJECTIVE: The purpose of this study was to determine the plasma clearance rate, systemic toxicity and histological effects of ICG-assisted laser therapy in an animal model. METHODS: Piglets received intravenous injection of ICG. Blood samples were collected at different times. Systemic toxicity was assessed by measuring liver enzyme levels and other indicators of liver function. The plasma clearance rate of ICG was determined by light absorption measurement in blood samples. The skin was irradiated with a diode laser (810 nm) using radiant exposures from 31 to 80 J/cm². Skin reaction at the treatment site was graded, and punch biopsies were taken for histological examination at 24 and 72 h after treatment. RESULTS: No hepatic toxicity was observed. The clinical examination revealed no adverse skin reactions at 24 or 72 h after laser irradiation. This was confirmed by histological evaluation that showed efficient vessel coagulation without damage of the epidermis or dermis. CONCLUSIONS: In light of these in vivo results, we suggest that ICG-assisted laser therapy could substantially improve clinical outcomes of PWS or leg veins treatment with minimal risk of adverse reactions.

A randomized two-sided placebo-controlled study on the efficacy and safety of atmospheric non-thermal argon plasma for pruritus.

BACKGROUND: To look into new potential indications for physical plasma and because some reports suggest plasma having antipruritic effects, we investigated the treatment of pruritus that often represents a therapeutic challenge. OBJECTIVES: To assess the efficacy and safety of cold atmospheric argon plasma as add-on-therapy in pruritic diseases. METHODS: We treated 46 patients with various pruritic diseases with cold plasma for 2 min daily in addition to standard treatment. All patients served as their own control, when their pruritic disease was treated with argon gas (placebo). The outcome measure was a long-term and short-term reduction in itching measured by means of a visual analogue score (VAS). RESULTS: The VAS scores at baseline were comparable (plasma 4.57, SD 2.38, argon 4.34, SD 2.35). We did not find any significant differences in VAS reduction between plasma and argon: long-term VAS difference of 1.97 (SD 1.33) for plasma and 1.74 (SD 2.37) for argon [P = 0.224, 95% CI: (-0.15; 0.60)], short-term VAS difference of 1.92 (SD 1.33) for plasma and 1.97 (SD 1.29) for argon [P = 0.544, 95% CI: (-0.21; 0.11)]. In both groups, patients experienced a significant reduction of pruritus at the end of therapy compared to baseline [plasma 1.97 (P < 0.0001), placebo 1.74 [P < 0.0001)]. No relevant side effects occurred, and treatment was well tolerated. CONCLUSIONS: Treatment with cold plasma did not result in higher pruritus reduction than treatment with placebo. A significant reduction of pruritus compared to no effect was found at the end of therapy in both groups. Both treatment options had similar safety profiles.

[Erythema scarlatiniforme desquamativum generalisatum]. / Erythema scarlatiniforme desquamativum generalisatum.

Erythema scarlatiniforme desquamativum generalisatum (Féréol-Besnier disease) is a rare skin disease characterized by generalized erythematous rash with subsequent desquamation. An 86-year-old woman presented with generalized erythema followed by an extensive, scarlatiniform peeling especially of the hands and feet. This generalized episode may be followed by erythema scarlatiniforme desquamativum localisatum recidivans, which is a recurring variant of the disease, localized to the hands and feet.

FGFR3, PIK3CA and RAS mutations in benign lichenoid keratosis.

BACKGROUND: Benign lichenoid keratoses (BLKs) are solitary skin lesions which have been proposed to represent a regressive form of pre-existent epidermal tumours such as solar lentigo or seborrhoeic keratosis. However, the genetic basis of BLK is unknown. OBJECTIVES: FGFR3, PIK3CA and RAS mutations have been shown to be involved in the pathogenesis of seborrhoeic keratosis and solar lentigo. We thus investigated whether these mutations are also present in BLK. METHODS: After manual microdissection and DNA isolation, 52 BLKs were screened for FGFR3, PIK3CA and RAS hotspot mutations using SNaPshot(®) multiplex assays. RESULTS: We identified 6/52 (12%) FGFR3 mutations, 10/52 (19%) PIK3CA mutations, 6/52 (12%) HRAS mutations and 2/52 (4%) KRAS mutations. FGFR3 and RAS mutations were mutually exclusive. One BLK showed a simultaneous PIK3CA and HRAS mutation. In nine BLKs with a mutation, nonlesional control tissue from the epidermal margin and the dermal lymphocytic infiltrate were wild-type, indicating that these mutations are somatic. To demonstrate that these findings are specific, 10 samples of lichen planus were analysed without evidence for FGFR3, PIK3CA or RAS mutations. CONCLUSIONS: Our results indicate that FGFR3, PIK3CA and RAS mutations are present in approximately 50% of BLKs. These findings support the concept on the molecular genetic level that at least a proportion of BLKs represents regressive variants resulting from former benign epidermal tumours such as seborrhoeic keratosis and solar lentigo.

Indocyanine green-augmented diode laser treatment of port-wine stains: clinical and histological evidence for a new treatment option from a randomized controlled trial.

BACKGROUND: Complete clearance of port-wine stains (PWS) is difficult to achieve, mainly because of the resistance of small blood vessels to laser irradiation. Indocyanine green (ICG)-augmented diode laser treatment (ICG+DL) may overcome this problem. OBJECTIVES: To evaluate the feasibility of ICG+DL therapy of PWS and to compare the safety and efficacy of ICG+DL with the standard treatment, flashlamp-pumped pulsed dye laser (FPDL). METHODS: In a prospective randomized controlled clinical study, 31 patients with PWS were treated with FPDL (λ(em)=585 nm, 6 J cm(-2) , 0.45 ms pulse duration) and ICG+DL (λ(em)=810 nm, 20-50 J cm(-2) , 10-25 ms pulse duration, ICG-concentration: 2 mg kg(-1) body weight) in a split-face modus in one single treatment setting that included histological examination (haematoxylin and eosin, CD34). Two blinded investigators and the patients assessed clearance rate, cosmetic appearance and side-effects up to 3 months after treatment. RESULTS: ICG+DL therapy induced photocoagulation of medium and large blood vessels (>20 µm diameter) but not of small blood vessels. According to the investigators' assessment, clearance rates and cosmetic appearance were better after ICG+DL therapy than after FPDL treatment (P=0.114, P=0.291, respectively), although not up to a statistically significant level, whereas patients considered these parameters superior (P=0.003, P=0.006, respectively). On a 10-point scale indicating pain during treatment, patients rated ICG+DL to be more painful (5.81 ± 2.12) than FPDL treatment (1.61 ± 1.84). CONCLUSION: ICG+DL represents a new and promising treatment modality for PWS, but laser parameters and ICG concentration need to be further optimized.

Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial.

BACKGROUND: The development of antibiotic resistance by microorganisms is an increasing problem in medicine. In chronic wounds, bacterial colonization is associated with impaired healing. Cold atmospheric plasma is an innovative promising tool to deal with these problems. OBJECTIVES: The 5-min argon plasma treatment has already demonstrated efficacy in reducing bacterial numbers in chronic infected wounds in vivo. In this study we investigated a 2-min plasma treatment with the same device and the next-generation device, to assess safety and reduction in bacterial load, regardless of the kind of bacteria and their resistance level in chronic wounds. METHODS: Twenty-four patients with chronic infected wounds were treated in a prospective randomized controlled phase II study with 2 min of cold atmospheric argon plasma every day: 14 with MicroPlaSter alpha device, 10 with MicroPlaSter beta device (next-generation device) in addition to standard wound care. The patient acted as his/her own control. Bacterial species were detected by standard bacterial swabs and bacterial load by semiquantitative count on nitrocellulose filters. The plasma settings were the same as in the previous phase II study in which wounds were exposed for 5 min to argon plasma. RESULTS: Analysis of 70 treatments in 14 patients with the MicroPlaSter alpha device revealed a significant (40%, P<0.016) reduction in bacterial load in plasma-treated wounds, regardless of the species of bacteria. Analysis of 137 treatments in 10 patients with the MicroPlaSter beta device showed a highly significant reduction (23.5%, P<0.008) in bacterial load. No side-effects occurred and the treatment was well tolerated. CONCLUSIONS: A 2-min treatment with either of two cold atmospheric argon plasma devices is a safe, painless and effective technique to decrease the bacterial load in chronic wounds.

Cytokines, chemokines and growth factors in wound healing.

In wound healing, a variety of mediators have been identified throughout the years. The mediators discussed here comprise growth factors, cytokines and chemokines. These mediators act via multiple (specific) receptors to facilitate wound closure. As research in the last years has led to many new findings, there is a need to give an overview on what is known, and on what might possibly play a role as a molecular target for future wound therapy. This review aims to keep the reader up to date with selected important and novel findings regarding growth factors, cytokines and chemokines in wound healing.

Skin signs in diabetes mellitus.

Diabetes mellitus is the most common endocrine disorder with continuously increasing prevalence. Blood vessels, nerves, eyes, kidneys and skin are affected, which causes both an enormous financial burden and a reduced quality of life of the affected patients. Long-standing diabetes may impair skin homeostasis resulting in skin manifestations in at least one third of all diabetics. The skin involvement may be the first presenting sign of diabetes, thus the respective skin signs should lead to diabetes focused diagnostic. Besides, the skin signs may be considered as a marker for the course of the disease or for the success of therapeutic interventions.

Off-label use of fumarate therapy for granulomatous and inflammatory skin diseases other than psoriasis vulgaris: a retrospective study.

BACKGROUND: Fumarates are approved for the systemic treatment of moderate and severe psoriasis vulgaris in Germany. However, a number of studies and case reports indicate their efficacy in the treatment of further inflammatory skin disorders or granulomatous skin diseases. OBJECTIVES: To examine the efficacy and safety of fumarates for the treatment of granulomatous and inflammatory skin diseases other than psoriasis vulgaris. PATIENTS AND METHODS: The therapeutic efficacy and side-effects of fumarate therapy were analysed retrospectively in patients with granuloma annulare (GA, n = 4), cutaneous sarcoidosis (SA, n = 1), lichen planus (LP, n = 3), pityriasis rubra pilaris (PRP, n = 1) or chronic discoid lupus erythematosus (CDLE, n = 1). RESULTS: Six patients (GA: 3/4; LP: 2/3; PRP: 1/1) showed complete clearance and two patients (GA: 1/3; SA: 1/1) had a partial response, and the CDLE patient showed stable disease under a combination therapy with hydroxychloroquine. Side-effects associated with fumarate therapy were seen in seven of ten patients and resolved spontaneously upon dose reduction or discontinuation of the therapy. CONCLUSION: According to this data, fumarates may represent a new approach in the treatment of granulomatous and inflammatory skin diseases other than psoriasis vulgaris. For the first time, the successful treatment of LP and CDLE with fumarates is reported. Side-effects are not limiting in most cases, but can hamper a dose escalation.

Development of a targeted risk-group model for skin cancer screening based on more than 100,000 total skin examinations.

BACKGROUND: Skin cancer screening aims to detect potentially metastasizing skin cancers at an early and surgically curable stage. This may take the form of mass screening, as currently occurs in Germany, or of targeted screening of those at greatest risk. OBJECTIVE: To develop a model to identify patients at high risk of developing skin cancer who would benefit from regular skin cancer screening. METHODS: This was an open prospective point-prevalence study of consecutive patients presenting to dermatologists for a total skin check. Demographic and skin cancer risk factors were recorded and, for the first time, histology of skin lesions was documented. Results were analysed by univariate and multivariate analyses and, after logistic regression with stepwise forward selection, a risk-group model was developed. RESULTS: The results of 108,281 total skin examinations were available for analysis. 142 definite melanomas, 108 severely dysplastic naevi/cannot-exclude-melanoma, 491 basal cell carcinomas (BCC) and 93 squamous cell carcinomas (SCC) were excised. A risk model was developed for melanoma and SCC based on mathematical e-functions. The model had >92% sensitivity for melanoma and SCC and an overall 67.24% specificity for melanoma, SCC and BCC. This targeted risk model identified one-third of the study population as being at risk for the development of melanoma and SCC. CONCLUSIONS: Using the risk calculator developed from this study, targeted screening of the identified at-risk population reduces the numbers needed to be screened regularly by 50%, yet has better sensitivity for melanoma and similar sensitivity for SCC compared to the current mass screening programme in Germany.

The impact of 10% α-hydroxy acid emulsion on skin pH.

BACKGROUND/AIMS: The effects of a 10% α-hydroxy acid (AHA) oil/water (O/W) emulsion on the pH of human skin surface (pH(ss)) and stratum corneum (SC; pH(sc)) were evaluated in vivo. METHODS: The AHA O/W emulsion was applied to an area on the volar forearm of male volunteers (n = 12), and then wiped off after 10 min. Prior to application and over the following 3 h, the pH(ss) was measured. We used glass electrode measurements and time domain dual lifetime referencing (tdDLR) with luminescent sensor foils. In another experiment (n = 5), the impact of the AHA O/W emulsion on the pH(sc) gradient was measured by tape stripping of the SC of the volar forearm after application of the AHA O/W emulsion. RESULTS: Compared with pH(ss) values prior to treatment [5.2 ± 1.7 (tdDLR) or 4.8 ± 0.5 (electrode)], the pH(ss) was significantly reduced 10 min after application [4.0 ± 0.3 (tdDLR) or 4.1 ± 0.1 (electrode)] and the pH(ss) remained significantly reduced over the measurement period of 3 h [after 3 h: 4.4 ± 0.2 (tdDLR) or 4.5 ± 0.3 (electrode)]. The AHA O/W emulsion significantly reduced the pH(sc) even down to deep layers of the SC. CONCLUSION: After a 10-min application time, the 10% AHA O/W emulsion reduces the pH(ss) (for at least 3 h) and pH(sc) in deep layers of the SC.

[New developments in laser therapy]. / Neue Entwicklungen in der Lasertherapie.

Based on the theory of stimulated emission of radiation that was proposed by Albert Einstein in 1916, the first lasers were developed in the 1960s. The first clinical use of laser technology in a German university took place in 1978 in the Department of Dermatology of the Ludwig-Maximilian-University in Munich under the guidance of the former director, Prof. Dr. med. Dr. h.c. mult. Otto Braun-Falco. In the following years, laser technology developed rapidly. Today laser technology is a widely used interdisciplinary therapeutic procedure that has deep clinical and scientific roots in dermatology. There are many conditions in both classic and aesthetic dermatology that are routinely - and sometimes exclusively - treated with lasers. Here we review recent developments in laser medicine. There seems to be a trend to combination procedures. To enhance efficacy, different laser systems are together or lasers are combined with specific topical medications.

Absence of BRAF and HRAS mutations in eruptive Spitz naevi.

BACKGROUND: Eruptive Spitz naevi have been reported rarely in the literature. In solitary Spitz naevi, BRAF and HRAS mutations, as well as increased copy numbers of chromosome 11p have been identified. OBJECTIVES: To investigate the genetic changes underlying eruptive Spitz naevi. METHODS: We report on a 16-year-old boy who developed multiple disseminated eruptive Spitz naevi within a few months. We analysed BRAF, HRAS, KRAS and NRAS genes in 39 naevi from this patient for hotspot mutations. Furthermore, comparative genomic hybridization analysis was performed in three lesions. RESULTS: None of the Spitz naevi displayed a mutation in the analysed genes, and no chromosomal imbalances were observed. Conclusions Our results indicate that the typical genetic alterations described in solitary Spitz naevi appear to be absent in eruptive Spitz naevi. Yet unknown alternative genetic alterations must account for this rare syndrome.

Skin ageing.

Similar to the entire organism, skin is subject to an unpreventable intrinsic ageing process. Additionally, skin ageing is also influenced by exogenous factors. Ultraviolet radiation in particular results in premature skin ageing, also referred to as extrinsic skin ageing or photoageing, which is the main cause of the changes associated with the ageing process in sun-exposed areas. Despite their morphological and pathophysiological differences, intrinsic and extrinsic ageing share several molecular similarities. The formation of reactive oxygen species and the induction of matrix metalloproteinases reflect the central aspects of skin ageing. Accumulation of fragmented collagen fibrils prevents neocollagenesis and accounts for the further degradation of the extracellular matrix by means of positive feedback regulation. The importance of extrinsic factors in skin ageing and the detection of its mechanisms have furthered the development of various therapeutic and preventive strategies.

A randomized clinical trial in psoriasis: synchronous balneophototherapy with bathing in Dead Sea salt solution plus narrowband UVB vs. narrowband UVB alone (TOMESA-study group).

BACKGROUND: Synchronous balneophototherapy (sBPT) simulates treatment conditions at the Dead Sea for outpatient use. In the past, sBPT proved to be an effective treatment for psoriasis. However, there is a lack of sufficiently large randomized controlled clinical trials evaluating the additional benefit of sBPT compared with ultraviolet B (UVB) monotherapy. OBJECTIVES: The purpose of this study was to compare the effectiveness and safety of sBPT with UVB phototherapy (PT) alone in a randomized controlled effectiveness study. METHODS: In this phase III, multicentre effectiveness study, 367 patients with moderate to severe psoriasis were randomly allocated in a 1 : 1 ratio to receive either sBPT consisting of narrowband UVB PT with 311 nm and synchronous bathing in 10% Dead Sea salt solution or PT with 311 nm alone. Primary endpoint, analysed on an intention-to-treat basis (n = 356), was the relative improvement of the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment (35 sessions or clearance). Sample size calculation aimed at the detection of superiority of at least 10%. RESULTS: Median PASI values were comparable at baseline (sBPT: 15.1, interquartile range: 10.9-24.3; PT: 15.3, interquartile range: 10.0-23.7). A clinically relevant and statistically significant difference of 49.5% between sBPT and PT could be proven at the end of the therapy phase (P < 0.001; Wilcoxon-Mann-Whitney test). Exploratory testing showed a statistically significant superiority of sBPT after 6 months. CONCLUSIONS: In routine clinical practice, sBPT is superior to PT alone after 35 treatment sessions and a follow-up of 6 months. Both treatments demonstrated to be safe.