Degree of Actinic Elastosis Is a Surrogate of Exposure to Chronic Ultraviolet Radiation and Correlates More Strongly with Cutaneous Squamous Cell Carcinoma than Basal Cell Carcinoma.

(1) Background: Keratinocyte cancer (KC) is associated with exposure to ultraviolet (UV) radiation. However, data are controversial as to whether chronic UV exposure or high intermittent UV exposure are key drivers of carcinogenesis in cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC). Prolonged sun exposure of the skin causes photo-aging, which is associated with actinic elastosis, a condition characterized by the degeneration of elastin in the upper dermis, which is assessable via conventional histology. In this study, we aimed to compare the degree of actinic elastosis in different types of KC with regard to various patient characteristics. (2) Methods: We defined a semiquantitative score for the degree of actinic elastosis ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration). The extent was measured histometrically by two independent dermatohistopathologists in the immediate vicinity of 353 KC. The scores were merged and matched with tumor types (cSCC and BCC with subtypes), and clinical variables such as body site, sex and age. (3) Results: As expected, the degree of actinic elastosis correlated with age. However, it was significantly higher in cSCC compared to BCC irrespective of age, sex, body site and tumor subtypes. (4): Conclusions: Lifetime sun exposure may be estimated via routine histology using this scoring technique for actinic elastosis as a surrogate marker. cSCCs are more strongly associated with chronic UV exposure than BCCs, even in sun-exposed localizations such as the face.

Phototherapy-induced elevation of serum level of melanoma inhibitory activity.

BACKGROUND: Phototherapy is a frequently used treatment modality for a variety of dermatologic diseases. UV radiation has different effects on the skin, for example increased production and release of cytokines and other proteins, and is involved in the initiation and progression of skin cancer. Objective of this clinical trial was to investigate potential systemic effects of UV phototherapy on cytokine profiles in blood. METHODS: In a prospective, mono-centric, one-armed study, the serum levels of the melanoma tumour marker "melanoma inhibitory activity" (MIA), Il-1α, Il-4, Il-6, Il-10, TNF-α and IFN-γ of 115 patients with different skin diseases were compared before and 24-48 hours as well as 2-4 weeks after the first phototherapy with PUVA (psoralen and ultraviolet A), UVA or UVB, or both. Data were analysed using linear mixed models. RESULTS: Estimated marginal means of MIA levels were 6.05 ng/mL (95%-CI: 5.37-6.72, range: 2.83-14.49) before the first treatment, which had significantly increased to 6.79 ng/mL 2-4 weeks after the first phototherapy (CI 95%: 6.12-7.47, range: 3.09-15.45; P = 0.0042). MIA levels 2-4 weeks after the first phototherapy were significantly higher than 24-48 hours after the first phototherapy (P = 0.0083). 2-4 weeks after the first treatment, TNF-α levels had decreased significantly (P = 0.033) more in patients with psoriasis who had responded well to phototherapy than in patients unresponsive to treatment. Serum levels of the other cytokines had not changed significantly. CONCLUSIONS: Short-term phototherapy significantly increased the serum levels of the melanoma tumour marker MIA. The potential clinical relevance of these findings (ie an increased risk of melanoma) is unclear and should be further investigated.

Fractional carbon dioxide laser resurfacing of skin grafts: long-term results of a prospective, randomized, split-scar, evaluator-blinded study.

BACKGROUND: Fractional ablative resurfacing is frequently used for treating atrophic and acne scars as well as for the early improvement of scars after surgery. No evidence-based clinical data on improving the appearance of skin grafts by fractional CO2 -laser resurfacing have been available so far. OBJECTIVES: The primary outcome parameter was the adaptation of the skin graft to the surrounding skin 2, 6, and 12 months after the second laser treatment. Secondary outcome parameters were melanin variation, skin roughness, resizing of the skin graft, and patient satisfaction with cosmetic results. METHODS: The randomized half of the skin graft was treated with the fractional CO2 -laser two times in a 4-week interval, whereby the first laser treatment was conducted 3-8 weeks after surgery. Two independent dermatologists assessed the adaptation of the treated area and the untreated control of the skin graft to the surrounding skin using follow-up pictures and an 11-point scale (0 representing no adaptation at all and 10 complete adaptation). RESULTS: Adaptation to the surrounding skin was significantly improved after laser therapy. The mean investigator ratings showed poor adaptation to the surrounding skin before the first treatment (treatment: 2.24 ± 1.00; control group: 1.95 ± 1.27; P < .001; n = 26) but significant improvement at the follow-up visits (8 weeks: treatment: 6.38 ± 1.47; control group 5.29 ± 1.27; P < .001; 6 months: treatment: 7.31 ± 1.24; control group 6.04 ± 0.91; 12 months: treatment: 7.6 ± 1.26; control group: 6.57 ± 1.02; n = 26). After fractional ablative laser treatment, appearance of the skin grafts was significantly improved for all time points. Profilometric analysis showed significantly reduced skin roughness 1 year after laser treatment compared to control (P = .003). Pigmentary irregularities were improved. Melanin distribution was significantly more uniform 1 year after laser treatment compared to control (P = .034). Patients were reasonably satisfied with both sides of the skin graft before treatment but more satisfied with the laser-treated side at the other time points (P < .001). CONCLUSIONS: Adaptation of the skin graft to the surrounding skin was significantly improved after ablative fractional skin resurfacing. Skin roughness and melanin variation were also improved. Patient satisfaction with the appearance of the skin graft was significantly higher after graft resurfacing. Thus, this treatment modality can be recommended for patients wishing to improve the appearance of their skin graft. Lasers Surg. Med. 50:1010-1016, 2018. © 2018 Wiley Periodicals, Inc.

KRAS, HRAS and EGFR Mutations in Sporadic Sebaceous Gland Hyperplasia.

Sporadic sebaceous gland hyperplasia (SGH) is a benign skin lesion, with a high prevalence in the general population. Although SGH has been attributed to both extrinsic and intrinsic factors, the underlying genetic changes have not yet been characterized. Recently, HRAS and KRAS mutations have been identified in sebaceous naevus, a hamartoma sharing histological characteristics with SGH. Therefore we screened 43 SGH for activating mutations in RAS genes and other oncogenes. We identified a wide spectrum of mutually exclusive activating HRAS (8/43), KRAS (11/43) and EGFR mutations (7/31) in altogether 60% of the lesions investigated. A RAS and EGFR wildtype status was found in 15 normal sebaceous glands in the head and neck area. Our findings indicate that activating HRAS, KRAS and EGFR mutations play a major role in the pathogenesis of sporadic SGH. These results support the concept that SGH is a true benign neoplasm rather than a reactive hyperplasia.

BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma.

Pyogenic granuloma (PG) is a common benign vascular skin lesion presenting as a rapidly growing angiomatous papule. The pathogenesis of most sporadic PGs and PGs associated with port wine stains (PWSs) remains elusive. We report that of 10 PGs secondarily arisen on a PWS, 8 showed a BRAF c.1799T>A (p.(Val600Glu)) and 1 a NRAS c.182A>G (p.(Gln61Arg)) mutation. The GNAQ c.548G>A mutation was identified in the PG and in the respective underlying PWS, indicating that PGs originate from cells of the PWS. In contrast to PG, 12 papulonodular lesions, which had developed in the PWSs of seven patients, showed a RAS and BRAF wild-type status. In sporadic PG we identified the BRAF c.1799T>A mutation in 3 of 25, a BRAF c.1391G>A mutation in 1 of 25, and a KRAS c.37G>C mutation in 1 of 25. Mutation-specific immunohistochemical detection of BRAF p.(Val600Glu) confirmed endothelial cells as carriers of the mutation in secondary and sporadic PG. Our study identifies the BRAF c.1799T>A mutation as a major driver mutation in the pathogenesis of, particularly, secondary PG. These data shed light on the hitherto undetermined genetic basis of PG and classify PG as a benign neoplasm.

Effects of cold atmospheric plasma (CAP) on ß-defensins, inflammatory cytokines, and apoptosis-related molecules in keratinocytes in vitro and in vivo.

Cold atmospheric plasma (CAP) has been gaining increasing interest as a new approach for the treatment of skin diseases or wounds. Although this approach has demonstrated promising antibacterial activity, its exact mechanism of action remains unclear. This study explored in vitro and in vivo whether CAP influences gene expression and molecular mechanisms in keratinocytes. Our results revealed that a 2 min CAP treatment using the MicroPlaSter ß in analogy to the performed clinical studies for wound treatment induces expression of IL-8, TGF-ß1, and TGF-ß2. In vitro and in vivo assays indicated that keratinocyte proliferation, migration, and apoptotic mechanisms were not affected by the CAP treatment under the applied conditions. Further, we observed that antimicrobial peptides of the ß-defensin family are upregulated after CAP treatment. In summary, our results suggest that a 2 min application of CAP induces gene expression of key regulators important for inflammation and wound healing without causing proliferation, migration or cell death in keratinocytes. The induction of ß-defensins in keratinocytes describes an absolutely new plasma strategy. Activation of antimicrobial peptides supports the well-known antibacterial effect of CAP treatment, whereas the mechanism of ß-defensin activation by CAP is not investigated so far.

Fractional carbon dioxide laser resurfacing of rhytides and photoaged skin--a prospective clinical study on patient expectation and satisfaction.

BACKGROUND: Fractional CO2 -laser resurfacing is increasingly used for treating rhytides and photoaged skin because of its favorable benefit-risk ratio. A key outcome measure and treatment goal in aesthetic laser therapy is patient satisfaction. However, few data are available on patient-reported outcomes after fractional ablative skin-resurfacing. OBJECTIVES: To compare patient expectations before and patient satisfaction after three fractional CO2 -laser treatments and to correlate objectively measured wrinkle reduction with patient satisfaction after treatment. METHODS: We investigated patient expectation and satisfaction using a 14-item questionnaire in 24 female patients. We assessed the skin-related quality of life and patient satisfaction with skin appearance. We profilometrically measured wrinkle size in four facial areas before and three months after treatment and investigated correlations between wrinkle reduction and patient satisfaction. RESULTS: The high patient expectations before treatment (ceiling effect) were actually slightly exceeded. The average score of 14 items delineating patient satisfaction with laser treatment was higher (4.64 ± 0.82; n = 24) than the respective expectations before treatment (4.43 ± 0.88; n = 24). Skin-related quality of life and patient satisfaction with skin appearance had significantly improved after the last treatment. Patients dissatisfied with their skin appearance before treatment (mean 2.1 ± 1.5; evaluated on a scale ranging from 0-6) were satisfied (mean 5.1 ± 1.2) (P < 0.001) with skin appearance at the follow-up. Patient satisfaction with skin appearance was not correlated to the profilometrically measured reduction of wrinkle size of any facial area. CONCLUSIONS: Our results show high patient satisfaction with ablative fractional skin resurfacing, also regarding improved self-esteem and self-satisfaction despite high pre-treatment expectations. Skin-specific quality of life had significantly improved. Thus, this treatment modality can be recommended for patients with photoaged skin wishing to improve skin appearance.

Activating mutations in the RAS/mitogen-activated protein kinase signaling pathway in sporadic trichoblastoma and syringocystadenoma papilliferum.

Trichoblastoma (TB) and syringocystadenoma papilliferum (SCAP) are both rare adnexal skin lesions occurring either sporadically or as secondary neoplasms in sebaceous nevi. TB and SCAP associated with sebaceous nevi have been shown to carry the same HRAS mutation as the underlying nevus. However, the genetic background of sporadic TB and SCAP has remained unknown. Therefore, we screened 18 sporadic TBs and 23 sporadic syringocystadenoma papillifera from 41 patients for the presence of activating mutations in RAS genes and other oncogenes. Using a RAS SNaPshot assay, HRAS mutations were detected in 2 (11%) of 18 sporadic TB and 6 (26%) of 23 sporadic syringocystadenoma papillifera. A KRAS mutation was identified in 1 sporadic SCAP. High-throughput oncogene mutation profiling furthermore identified BRAF V600E mutations in sporadic syringocystadenoma papillifera, which could be validated in 12 (52%) of 23 lesions using a BRAF SNaPshot assay. BRAF and RAS mutations were mutually exclusive in sporadic syringocystadenoma papillifera. No BRAF mutation could be detected in 3 syringocystadenoma papillifera secondarily arisen from a sebaceous nevus as well as in sporadic TB. In 14 lesions carrying an oncogenic mutation, nonlesional control tissue from the epidermal margin revealed a wild-type sequence, thus proving the somatic character of the mutation. Our results indicate that activation of the RAS-mitogen-activated protein kinase pathway by BRAF and RAS mutations contributes significantly to the tumorigenesis of sporadic SCAP and, less frequently, of sporadic TB.

CHILD syndrome with mild skin lesions: histopathologic clues for the diagnosis.

CHILD syndrome is an acronym signifying congenital hemidysplasia with ichthyosiform nevus and limb defects. A 27-year-old woman presented with chronic verrucous and hyperkeratotic skin lesions involving the left genital area, left hand and left foot since childhood. The histopathologic findings were consistent with verruciform xanthoma. In correlation with the clinical picture of a linear lesion, the diagnosis of CHILD nevus was made. Subsequent genetic analysis identified a germline c.324C>T (p.A105V) NSDHL mutation and confirmed a diagnosis of CHILD syndrome. This syndrome can be associated with only minimal clinical symptoms. The anatomical distribution of the lesions, a static clinical course and the typical histopathologic features of a CHILD nevus can serve as the clue to a diagnosis of CHILD syndrome in such cases.

Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic wounds that disrupt epidermal repair.

Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing. Extracellular pH (pHe) is precisely regulated and potentially important in signaling within wounds due to its diverse cellular effects. Additionally, sufficient oxygenation is a prerequisite for cell proliferation and protein synthesis during tissue repair. It was, however, impossible to study these parameters in vivo due to the lack of imaging tools. Here, we present luminescent biocompatible sensor foils for dual imaging of pHe and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI), respectively. With these dual sensors, we discovered centripetally increasing pHe-gradients on human chronic wound surfaces. In a therapeutic approach, we identify pHe-gradients as pivotal governors of cell proliferation and migration, and show that these pHe-gradients disrupt epidermal barrier repair, thus wound closure. Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe-gradients in perturbed healing. We also found that pHe-gradients on chronic wounds of humans are predominantly generated via centrifugally increasing pHe-regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of pHe on chronic wound surfaces poses a promising strategy to improve healing. The study has broad implications for cell science where spatial pHe-variations play key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented herein can be used to visualize pHe and oxygenation in various biomedical fields.

Black tattoos entail substantial uptake of genotoxicpolycyclic aromatic hydrocarbons (PAH) in human skin and regional lymph nodes.

Hundreds of millions of people worldwide have tattoos, which predominantly contain black inks consisting of soot products like Carbon Black or polycyclic aromatic hydrocarbons (PAH). We recently found up to 200 µg/g of PAH in commercial black inks. After skin tattooing, a substantial part of the ink and PAH should be transported to other anatomical sites like the regional lymph nodes. To allow a first estimation of health risk, we aimed to extract and quantify the amount of PAH in black tattooed skin and the regional lymph nodes of pre-existing tattoos. Firstly, we established an extraction method by using HPLC-DAD technology that enables the quantification of PAH concentrations in human tissue. After that, 16 specimens of human tattooed skin and corresponding regional lymph nodes were included in the study. All skin specimen and lymph nodes appeared deep black. The specimens were digested and tested for 20 different PAH at the same time.PAH were found in twelve of the 16 tattooed skin specimens and in eleven regional lymph nodes. The PAH concentration ranged from 0.1-0.6 µg/cm2 in the tattooed skin and 0.1-11.8 µg/g in the lymph nodes. Two major conclusions can be drawn from the present results. Firstly, PAH in black inks stay partially in skin or can be found in the regional lymph nodes. Secondly, the major part of tattooed PAH had disappeared from skin or might be found in other organs than skin and lymph nodes. Thus, beside inhalation and ingestion, tattooing has proven to be an additional, direct and effective route of PAH uptake into the human body.

Diet-induced pigmented purpuric dermatosis.

Pigmented purpuric dermatoses (PPD) are chronic and relapsing disorders characterised by a localised or generalised purpuric rash. Even though the clinical presentation of PPD subtypes varies, they have a similar histopathology. The aetiology is largely unknown, but trigger factors, such as drugs, infections and systemic illnesses have been described. To our knowledge, this is the only case showing widespread PPD lesions not only induced but also rapidly provoked by dietary factors, namely Coca Cola and apple-cherry fruit spritzer.

Low incidence of oncogenic EGFR, HRAS, and KRAS mutations in seborrheic keratosis.

Seborrheic keratosis (SK) represents a frequent epidermal skin tumor. Although lacking a malignant potential, these tumors reveal multiple oncogenic mutations. A previous study identified activating mutations in 89% of SK, particularly in FGFR3 and PIK3CA genes. The aim of this study was to identify further oncogenic mutations in human SK. Therefore, we screened for mutations in EGFR, FGFR2, PIK3R1, HRAS, KRAS, and NRAS genes using both Sanger sequencing of selected exons and a multiplex SNaPshot assay in 58 SK of 14 patients. We identified a somatic EGFR p.L858R mutation in 1 SK. Furthermore, the HRAS mutations p.G13R (2/58 SK) and p.Q61L (2/58 SK) were found. These mutations have not been described in human SK yet. In addition, 1 SK revealed the KRAS p.G12V mutation, which has already been reported in SK. No mutations were detected in FGFR2, PIK3R1, and NRAS genes. The results of this study suggest that activating mutations of EGFR, HRAS, and KRAS contribute to the pathogenesis of human SK, although at a lower frequency than FGFR3 and PIK3CA mutations. FGFR2, PIK3R1, and NRAS mutations obviously do not have a significant role in the development of SK.

An Internet-based survey on characteristics of laser tattoo removal and associated side effects.

Tattoo removal by laser therapy is a frequently performed procedure in dermatological practices. Quality-switched ruby, alexandrite, or Nd:YAG lasers are the most suitable treatment devices. Although these techniques are regarded as safe, both temporary and permanent side effects might occur. Little has been published on the frequency of complications associated with laser tattoo removal. We performed an Internet survey in German-speaking countries on characteristics of laser tattoo removal and associated side effects. A total number of 157 questionnaires entered the final analysis. Motivations for laser tattoo removal were mainly considering the tattoo as youthful folly (29%), esthetic reasons (28%), and 6% indicated medical problems. One third of participants were unsatisfied with the result of laser tattoo removal, and a complete removal of the tattoo pigment was obtained in 38% only. Local transient side effects occurred in nearly all participants, but an important rate of slightly visible scars (24%) or even important scarring (8%) was reported. Every fourth participant described mild or intense tan when the laser treatment was performed, and the same number of people indicated UV exposure following laser therapy, which should normally be avoided in these circumstances. As reported in the literature, nearly half of the participants experienced hypopigmentation in the treated area. Our results show that from the patients' point of view there is an important rate of side effects occurring after laser tattoo removal. Appropriate pretreatment counseling with regard to realistic expectations, possible side effects, and the application of test spots is mandatory to ensure patient satisfaction. Laser treatment should be performed by appropriately trained personnel only.

Contact-free inactivation of Trichophyton rubrum and Microsporum canis by cold atmospheric plasma treatment.

AIM: Cold atmospheric plasma (CAP) has already proven efficient at disinfection of microorganisms including biofilms. The objective of the present study is to assess the efficacy of CAP against the dermatophytes Trichophyton rubrum and Microsporum canis in vitro. MATERIALS & METHODS: T. rubrum and M. canis were exposed to CAP for different treatment times and time intervals in vitro. Treatment with ciclopirox olamine or UVC radiation (0.120 J/cm(2)) served as controls. CAP was generated by the surface microdischarge technology. Fungal colony growth was measured upon CAP treatment. RESULTS: Repeated daily CAP treatments of 10 min demonstrated an inhibition of growth during the treatment period of 9 days. Single CAP treatment sessions for 5, 8 and 10 min, as well as treatments for 5 or 8 min daily, resulted in less fungal growth inhibition. UVC radiation treatment failed, but not ciclopirox olamine. CONCLUSION: CAP shows promising potential for future application in the treatment of dermatophyte infections.

Randomized placebo-controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites.

Cold atmospheric plasma has already been shown to decrease the bacterial load in chronic wounds. However, until now it is not yet known if plasma treatment can also improve wound healing. We aimed to assess the impact of cold atmospheric argon plasma on the process of donor site healing. Forty patients with skin graft donor sites on the upper leg were enrolled in our study. The wound sites were divided into two equally sized areas that were randomly assigned to receive either plasma treatment or placebo (argon gas) for 2 minutes. Donor site healing was evaluated independently by two blinded dermatologists, who compared the wound areas with regard to reepithelialization, blood crusts, fibrin layers, and wound surroundings. From the second treatment day onwards, donor site wound areas treated with plasma (n = 34) showed significantly improved healing compared with placebo-treated areas (day 1, p = 0.25; day 2, p = 0.011; day 3, p < 0.001; day 4, p < 0.001; day 5, p = 0.004; day 6, p = 0.008; day 7, p = 0.031). Positive effects were observed in terms of improved reepithelialization and fewer fibrin layers and blood crusts, whereas wound surroundings were always normal, independent of the type of treatment. Wound infection did not occur in any of the patients, and no relevant side effects were observed. Both types of treatment were well tolerated. The mechanisms contributing to these clinically observed effects should be further investigated.

Evidence-based topical management of chronic wounds according to the T.I.M.E. principle.

The number of patients suffering from chronic wound healing disorders in Germany alone is estimated to be 2.5-4 million. Therapy related expenses reach 5-8 billion Euros annually. This number is partially caused by costly dressing changes due to non-standardized approaches and the application of non-evidence-based topical wound therapies. The purpose of this paper is to elucidate a straightforward principle for the management of chronic wounds, and to review the available evidence for the particular therapy options. The T.I.M.E.-principle (Tissue management, Inflammation and infection control, Moisture balance, Epithelial [edge] advancement) was chosen as a systematic strategy for wound bed preparation. Literature was retrieved from the PubMed and Cochrane Library databases and subjected to selective analysis. Topical wound management should be carried out according to a standardized principle and should further be synchronized to the phases of wound healing. Despite the broad implementation of these products in clinical practice, often no benefit exists in the rate of healing, when evaluated in meta-analyses or systematic reviews. This insufficient evidence is additionally limited by varying study designs. In case of non-superiority, the results suggest to prefer relatively inexpensive wound dressings over expensive alternatives. Arbitrary endpoints to prove the effectiveness of wound dressings, contribute to the random use of such therapies. Defining rational endpoints for future studies as well as the deployment of structured therapy strategies will be essential for the economical and evidence-based management of chronic wounds.

Adverse reactions after tattooing: review of the literature and comparison to results of a survey.

The number of tattooed people has substantially increased in the past years. Surveys in different countries reveal this to be up to 24% of the population. The number of reported adverse reactions after tattooing has also increased including infections, granulomatous and allergic reactions and tumors. However, the case reports do not reflect the frequency of adverse reactions. This review compares the medically documented adverse reactions published in 1991-2011 with the findings of a nation-wide survey that recently revealed the features and health problems associated with tattoos. To compare the data with the survey, the sex of patients was reported and the location and color of tattoos were evaluated. The results show clearly that colored tattoo inks are mainly responsible for adverse skin reactions and that tattoos on the extremities are involved most.

A randomized controlled trial to optimize indocyanine green-augmented diode laser therapy of capillary malformations.

BACKGROUND: Indocyanine green (ICG)-augmented diode laser therapy (ICG + DL) represents a new treatment modality for capillary malformations (CM). However, an increase of the ICG-concentration or the use of an intense pulsed light (IPL) device as light source may further optimize treatment outcomes in CM. OBJECTIVE: This proof-of-concept trial including 15 patients (skin type II to III) with CM evaluated the efficacy and safety of ICG-augmented diode laser therapy (808 nm) at a total dose of 4 mg/kg body weight (b.w.). Additionally, five patients with extensive CM received IPL therapy before and after ICG-administration (ICG + IPL). METHODS: ICG was intravenously administered to 15 patients with CM at a total dose of 4 mg/kg b.w. Immediately after ICG injection, diode laser pulses with different radiant exposures (20-110 J/cm(2) ) were applied as one single treatment. Five patients with extensive CM additionally received IPL (555-950 nm) therapy. Safety and efficacy were assessed both 1 and 3 months after the single treatment by a blinded investigator and the patient. Furthermore, color of the CM was objectively measured by means of a color meter (colorStriker™, Eduard Mathai GmbH, Hannover, Germany). Treatment with the flashlamp-pumped pulsed dye laser (FPDL) and the IPL alone (five patients) served as reference treatment. RESULTS: According to the assessment by the patients and the blinded investigator, the clearance rate was slightly better after ICG + DL therapy than after FPDL treatment (P = 0.1, P = 0.8). In one out of five patients, IPL with and without ICG injection induced poor to moderate clearance of CM and persisting erythema in another patient. The correlation between the visual assessment by the blinded investigator and the colorimetric measurements was poor. CONCLUSION: A minority of patients with CM may benefit from ICG + DL therapy, but efficacy cannot be improved by higher ICG doses.