Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research: an interdisciplinary perspective.

More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts.

Atopic dermatitis (AD), and psoriasis are long-term skin conditions that can significantly affect people's lives, especially when symptoms are severe. Approximately 10% of adults and 20% of children are affected by AD, while psoriasis affects around 5% of people in the UK. Both conditions are associated with debilitating physical symptoms (such as itch) and have been linked to depression and anxiety. Biomarkers are naturally occurring chemicals in the human body and have potential to enhance the longer-term management of AD and psoriasis. Currently, there are no routinely used biomarkers that can identify people who experience or will go on to develop severe AD and psoriasis. For this reason, research is under way to understand which biomarkers are linked to severity. In this study, a multidisciplinary team of skin researchers from across Europe, along with patient groups, discussed the complexities of studying severity-related biomarkers. We identified a number of severity measurement approaches and there were recommendations for future biomarker research, including (i) considering multiple measures as no single measure can encompass all aspects of severity, (ii) exploring severity measures recorded by both healthcare professionals and patients, as each may capture different aspects, and (iii) accounting for influencing factors, such as different treatment approaches, that may impact AD and psoriasis severity, which make it challenging to compare findings across studies. Overall, we anticipate that the insights gained from these discussions will increase the likelihood of biomarkers being effectively applied in real-world settings, to ultimately improve outcomes for people with AD and psoriasis.

Mapping exercise and status update of eight established registries within the TREatment of ATopic eczema Registry Taskforce.

BACKGROUND: The TREatment of ATopic eczema (TREAT) Registry Taskforce is a collaborative international network of registries collecting data of atopic eczema (AE) patients receiving systemic and phototherapy with the common goal to provide long-term real-world data on the effectiveness, safety and cost-effectiveness of therapies. A core dataset, consisting of domains and domain items with corresponding measurement instruments, has been developed to harmonize data collection. OBJECTIVES: We aimed to give an overview of the status and characteristics of the eight established TREAT registries, and to perform a mapping exercise to examine the degree of overlap and pooling ability between the national registry datasets. This will allow us to determine which research questions can be answered in the future by pooling data. METHODS: All eight registries were asked to share their dataset and information on the current status and characteristics. The overlap between the core dataset and each registry dataset was identified (according to the domains, domain items and measurement instruments of the TREAT core dataset). RESULTS AND CONCLUSIONS: A total of 4702 participants have been recruited in the eight registries as of 1st of May 2022. Of the 69 core dataset domain items, data pooling was possible for 69 domain item outcomes in TREAT NL (the Netherlands), 61 items in A-STAR (UK and Ireland), 38 items in TREATgermany (Germany), 36 items in FIRST (France), 33 items in AtopyReg (Italy), 29 items in Biobadatop (Spain), 28 items in SCRATCH (Denmark) and 20 items in SwedAD (Sweden). Pooled analyses across all registries can be performed on multiple important domain items, covering the main aims of analysing data on the (cost-)effectiveness and safety of AE therapies. These results will facilitate future comparative or joint analyses.

Rarities in rare: illuminating the microvascular and dermal status in juvenile localised scleroderma. A case series.

OBJECTIVES: To assess the (structural and functional) characteristics of the microvascular and dermal status in juvenile localised scleroderma (jLoS), using novel non-invasive standardised research tools commonly used in adult systemic sclerosis (SSc). METHODS: Ten consecutive patients with a confirmed jLoS diagnosis were studied cross-sectionally in this two-centre case series. For each patient, the most prominent lesion (i.e., "target lesion") was chosen for further examination of the centre, edge and contralateral unaffected site. High-frequency ultrasonography was used to determine dermal thickness, durometer for skin hardness, and laser speckle contrast analysis (LASCA) for a dynamical evaluation of the microcirculation. The structure of the microcirculation was evaluated at the nailfolds of the 2nd-5th finger bilaterally, using nailfold videocapillaroscopy (NVC). RESULTS: 6 linear and 4 plaque subtype jLoS lesions were included. Dermal thickness was thinner at the centre of the "target lesions" vs. the edges (p<0.001) and control sites (p<0.001). Skin hardness was harder at the centre of the "target lesions" vs. the edges (p=0.012) and control sites (p=0.003). A higher perfusion was found in the centre of the "target lesion" (124.87±66.40 PU) vs. the edges (87.27±46.40 PU; p<0.001) and control sites (67.85±37.49; p<0.001). Of note, all patients had a "non-scleroderma" pattern on NVC. CONCLUSIONS: This case series suggests the supportive value of both microcirculatory and dermal assessments of skin lesions using novel non-invasive research tools, adopted from adult SSc, for (j)LoS.

Long-term effectiveness and safety of treatment with dupilumab in patients with atopic dermatitis: Results of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry.

BACKGROUND: Evidence on long-term dupilumab treatment for atopic dermatitis in daily practice is lacking. OBJECTIVE: To investigate patient characteristics, treatment aspects, effectiveness, and safety of up to 84 weeks of dupilumab treatment. METHODS: An observational prospective cohort study was conducted of patients with atopic dermatitis starting dupilumab in routine clinical care. RESULTS: Of the 221 included patients, 103 used systemic therapy at baseline. At 84 weeks, we found a change of -15.2 (SE, 1.7) for the Eczema Area and Severity Index, -16.9 (SE, 1.4) for the Patient-Oriented Eczema Measure, and -17.2 (SE, 1.6) for the Dermatology Life Quality Index. We found a trend for improvement over time for the Investigator Global Assessment and Numerical Rating Scale for pruritus. Severe (n = 79) including serious (n = 11) adverse events were observed in 69 patients. Eye complaints were most frequently reported (n = 46). Twenty-one patients adjusted the regular dosing schedule, and 14 patients discontinued treatment, mainly due to ineffectiveness (n = 7). LIMITATIONS: Only adverse events of severe and serious nature were registered for feasibility reasons. CONCLUSION: Daily practice dupilumab treatment of up to 84 weeks is generally well-tolerated, apart from the reporting of eye complaints. It can be considered a long-term effective treatment for atopic dermatitis in combination with topical and initial concomitant systemic treatment, showing a sustained improvement of signs, symptoms, and quality of life.

House dust mite allergens Der f and Der p induce IL-31 production by blood-derived T cells from atopic dermatitis patients.

Aero-allergens, such as house dust mite (HDM), have been suggested to play a role in the initiation of atopic dermatitis (AD)-related skin inflammation. Here, we analysed the proliferation and the cytokine expression of blood-derived T cells from AD and healthy individuals upon HDM-allergen stimulation. The proliferating cells from healthy individuals and AD patients had a significantly different, distinct cytokine profile: in AD blood, we found increased frequencies of HDM-reactive IL-31-producing T cells, as well as a decreased Th1/Th2 and Tc1/Tc2 ratio, suggesting that allergen-specific T cells in blood of chronic AD patients are subject to pre-existent Th2-Tc2 and "Th31-Tc31" programming.

Contact sensitization in Dutch children and adolescents with and without atopic dermatitis - a retrospective analysis.

BACKGROUND: Allergic contact dermatitis is known to occur in children with and without atopic dermatitis, but more data are needed on contact sensitization profiles in these two groups. OBJECTIVES: To identify frequent allergens in children with and without atopic dermatitis suspected of having allergic contact dermatitis. METHODS: A retrospective analysis of children aged 0-17 years patch tested between 1996 and 2013 was performed. RESULTS: Of all 1012 children tested because of suspected contact dermatitis, 46% developed one or more positive reactions, the proportions for children with (n = 526) and without (n = 395) atopic dermatitis being 48% and 47%, respectively. Children with atopic dermatitis reacted more often to lanolin alcohol (30% pet., p = 0.030), Amerchol L-101 (p = 0.030), and fragrances [fragrance mix I (p = 0.048) and Myroxylon pereirae (p = 0.005)]. Allergens outside the European baseline series that frequently gave positive reactions in these groups included cocamidopropyl betaine and Amerchol L-101. Reactivity to these allergens was significantly more common in atopic dermatitis children. CONCLUSION: Sensitization prevalences in children with and without atopic dermatitis were similar, but children with atopic dermatitis reacted significantly more often to lanolin alcohol and fragrances. Testing with additional series besides the European baseline series may be necessary, as reactions to, for example, cocamidopropyl betaine and Amerchol L-101 may otherwise be missed.

Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types.

Background: Few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types. Objective: To investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type. Methods: In an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.nl) and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register; astar-register.org) registries, data on morphological phenotypes and treatment outcomes were investigated. Results: A total of 235 patients were included (light skin types [LST]: Fitzpatrick skin type 1-3, n = 156 [Ethnicity, White: 94.2%]; dark skin types [DST]: skin type 4-6, n = 68 [Black African/Afro-Caribbean: 25%, South-Asian: 26.5%, and Hispanics: 0%]). DST were younger (19.5 vs 29.0 years; P < .001), more often had follicular eczema (22.1% vs 2.6%; P < .001), higher baseline Eczema Area and Severity Index (EASI) scores (20.1 vs 14.9; P = .009), less allergic contact dermatitis (30.9% vs 47.4%; P = .03), and less previous phototherapy use (39.7% vs 59.0%; P = .008). When comparing DST and LST corrected for covariates including baseline EASI, DST showed greater mean EASI reduction between baseline and 6 months with only dupilumab (16.7 vs 9.7; adjusted P = .032). No differences were found for adverse events for any treatments (P > .05). Limitations: Unblinded, non-randomized. Conclusion: Atopic dermatitis differs in several characteristics between LST and DST. Skin type may influence treatment effectiveness of dupilumab.

Increased frequencies of IL-31-producing T cells are found in chronic atopic dermatitis skin.

Interleukin (IL)-31 has been associated with pruritus, a characteristic feature of atopic dermatitis (AD). Local T cell responses may be responsible for the increased level of IL-31 mRNA observed in AD. We investigated the frequency of IL-31-producing T cells in AD lesions, as well as their cytokine profile. T cells were isolated from chronic AD lesions, autologous blood and healthy donor skin. Intracellular expression of IL-31, IFN-γ, IL-13, IL-17 and IL-22 was measured using flow cytometry. T cells from AD lesions contained significantly higher percentages of IL-31-producing T cells compared to autologous blood and donor skin. Many IL-31-producing T cells co-produced IL-13 and to lesser extent IL-22, but rarely IFN-γ or IL-17. A substantial part of the IL-31-producing T cells did not co-produce any of the other cytokines and could therefore not be linked to any of the known functionally different T cell subsets. The T cell infiltrates were also relatively enriched for Th2/Tc2 and Th22/Tc22 cells, while frequencies of Th1/Tc1 and Th17 cells were decreased. This is the first report describing the detection of IL-31 at protein level in skin-infiltrating T cells. We show here that T cells in chronic AD skin produce IL-31 and that AD lesions contain increased levels of these IL-31-producing T cells. This suggests that a substantial part of previously reported increased IL-31 mRNA levels in AD skin is T cell derived and that these cells may be involved in the pathogenesis of AD.

Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus: important lessons from longitudinal follow-up.

OBJECTIVES: To observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features. METHODS: Clinical and (yearly) capillaroscopy data from a longitudinal cohort of patients with cSLE (minimum of four Systemic Lupus International Collaborating Clinics (SLICC) criteria, onset <18 years) were analysed. Disease activity was measured by Systemic Lupus Erythematosus Activity Index (SLEDAI) and disease damage by SLICC Damage Index. A scleroderma pattern was defined according to the 'fast track algorithm' from the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases. An abnormal capillary pattern, not matching a scleroderma pattern, was defined as 'microangiopathy'. RESULTS: Our cohort consisted of 53 patients with cSLE with a median disease onset of 14 years (IQR 12.5-15.5 years), median SLEDAI score at diagnosis was 11 (IQR 8-16), median SLEDAI at follow-up was 2 (IQR 1-6). A scleroderma pattern (ever) was seen in 18.9%, while only 13.2% of patients had a normal capillary pattern. Thirty-three patients had follow-up capillaroscopy of which 21.2% showed changes in type of capillary pattern over time. Type of capillary pattern was not associated with disease activity. Raynaud's phenomenon (ever) was equally distributed among patients with different capillaroscopy patterns (p=0.26). Anti-ribonucleoprotein antibodies (ever) were significantly more detected (Χ2, p=0.016) in the scleroderma pattern subgroup (n=7 of 10, 70%). Already 5 years after disease onset, more than 50% of patients with a scleroderma pattern had SLE-related disease damage (HR 4.5, 95% CI 1.1 to 18.8, p=0.034), but they did not develop clinical features of systemic sclerosis at follow-up. Number of detected fingers with a scleroderma pattern was similar between cSLE, juvenile systemic sclerosis and juvenile undifferentiated connective tissue disease. CONCLUSION: This longitudinal study shows that the majority of capillary patterns in cSLE are abnormal and they can change over time. Irrespective of disease activity, a capillary scleroderma pattern in cSLE may be associated with higher risk of SLE-related disease damage.

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.

Work ability and quality of working life in atopic dermatitis patients treated with dupilumab.

Atopic dermatitis is associated with work productivity loss. Little is known about how patients perceive their work ability and quality of working life, and how this is affected by treatment. Our primary objective was to investigate work ability and quality of working life at baseline and during treatment in the long term. A registry-embedded prospective observational cohort study was conducted consisting of patients with atopic dermatitis starting dupilumab in routine clinical care. The instruments used were the Work Ability Index (WAI; questions 1, 2, and 3) and the Quality of Working Life Questionnaire (QWLQ). Ninety-three patients were included of whom 72 were (self-)employed (77%). From baseline to 48 weeks, the mean WAI-1 score (general work ability, range 0-10) improved from 6.8 (±2.0) to 7.9 (±1.3), WAI-2 (physical work ability, range 1-5) from 3.7 (±0.9) to 4.3 (±0.7), and WAI-3 (mental/emotional work ability, range 1-5) from 3.4 (±0.9) to 3.9 (±0.8) (p = 0.001, p = 0.005, p < 0.001, respectively). The mean QWLQ total score improved from 74.0 (±9.1) to 77.5 (±9.6) and subscale "Problems due to health situation" improved from 37.4 (±22.3) to 61.5 (±23.1) (range 0-100; p = 0.032, p < 0.001, respectively). In conclusion, patients with moderate-to-severe atopic dermatitis starting dupilumab report decreased work ability and quality of working life, mainly due to health-related problems. Significant improvement of work ability and quality of working life is observed with dupilumab treatment.

Atopic eczema or atopiform dermatitis.

Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL-31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation-regulated chemokine (TARC) and proliferating-inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric views on pathogenesis (the inside-outside paradigm) and the diagnostic entity atopiform dermatitis (AFD) are discussed here. We emphasize that diagnosing AE is not simple but challenging. We accentuate that a diagnosis of AE is only possible when there is allergen-specific IgE. Advice as to the need for elimination of allergens and adjustment of lifestyle are only proficient in patients having atopy and true AE, not in those having AFD.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema registries.

BACKGROUND: Patients with moderate-to-severe atopic eczema (AE) often require photo- or systemic immunomodulatory therapies to induce disease remission and maintain long-term control. The current evidence to guide clinical management is small, despite the frequent and often off-label use of these treatments. Registries of patients on photo- and systemic immunomodulatory therapies could fill this gap, and the collection of a core set concerning these therapies in AE will allow direct comparisons across registries as well as data sharing and pooling. Using an eDelphi approach, the international TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek consensus between key stakeholders internationally on a core set of domains and domain items for AE patient registries with a research focus that collect data of children and adults on photo- and systemic immunomodulatory therapies. METHODS/DESIGN: Participants from six stakeholder groups will be invited: doctors, nurses, non-clinical researchers, patients, as well as industry and regulatory body representatives. The eDelphi will comprise three sequential online rounds, requesting participants to rate the importance of each proposed domain and domain items. Participants will be able to add domains and domain items to the proposed list in round 1. A final consensus meeting will be held with representatives of each stakeholder group. DISCUSSION: Identifying a uniform core set of domains and domain items to be captured by AE patient registries will increase the utility of individual registries, and provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies to guide clinical management across dermatology centres and country borders. TRIAL REGISTRATION: Not applicable. This eDelphi study was registered in the Core Outcome Measures for Effectiveness Trials (COMET) database.

Detection of UV-induced pigmentary and epidermal changes over time using in vivo reflectance confocal microscopy.

In vivo reflectance confocal microscopy (RCM) provides high-resolution optical sections of the skin in its native state, without needing to fix or section the tissue. Melanin provides an excellent contrast for RCM, giving a bright signal in the confocal images. The pigmented guinea-pig is a common animal model to study human pigment induction and modulation, as its tanning response is comparable to human tanning after exposure to ultraviolet radiation (UVR). We investigated the applicability of RCM to detecting UVR-induced pigmentary changes in this model. Animals were exposed to solar simulator radiation for 7 days. RCM was performed during the irradiation and follow-up period. Compared to non-irradiated skin, an increase in melanocyte size, dendricity, and number, as well as increased pigment in keratinocytes, was seen in the irradiated epidermis. Interestingly, these changes could be detected even before a tanning response was clinically visible. UVR-induced epidermal hyperplasia could also be detected and quantified. In conclusion, in vivo RCM is a sensitive non-invasive imaging technique that can repeatedly measure epidermal pigmentation and thickness, as demonstrated in the guinea-pig model. This technique should greatly enhance our appreciation of dynamic pigmentary changes in human or animal skin over time and in response to specific stimuli.

Topical application of a protein kinase C inhibitor reduces skin and hair pigmentation.

To determine whether inhibition of PKC-beta activity decreases pigmentation, paired cultures of primary human melanocytes were first pretreated with bisindolylmaleimide (Bis), a selective PKC inhibitor, or vehicle alone for 30 min, and then treated with TPA for an additional 90 min to activate PKC in the presence of Bis. Bis blocked the expected induction of tyrosinase activity by activation of PKC. Addition of a peptide corresponding to amino acids 501-511 of tyrosinase containing its PKC-beta phosphorylation site, a presumptive PKC-beta pseudosubstrate, gave similar results. To determine whether Bis reduces pigmentation in vivo, the backs of four shaved and depilated pigmented guinea pigs were UV irradiated with a solar simulator for 2 wk excluding weekends. Compared to vehicle alone, Bis (300 microM), applied twice daily to paired sites for various periods encompassing the irradiation period, decreased tanning. Bis also, although less strikingly, reduced basal epidermal melanin when topically applied twice daily, 5 d per wk, for 3 wk to shaved and depilated unirradiated skin. Moreover, topical application of Bis (100 microM) once daily for 9 d to the freshly depilated backs of 8-wk-old mice markedly lightened the color of regrowing hair. These results demonstrate that inhibiting PKC activity in vivo selectively blocks tanning and reduces basal pigmentation in the epidermis and in anagen hair shafts.

Photodynamic therapy for cutaneous proliferative vascular tumors in a mouse model.

Photodynamic therapy with benzoporphyrin derivative monoacid ring A and red light (PDT-BPD) has been used to treat human choroidal hemangiomas, and may be useful for cutaneous vascular lesions. The potential for PDT-BPD to inhibit selectively vascular tumor growth was tested in a mouse angiosarcoma model, of which the tumor growth mimics the proliferative phase of hemangiomas. Vascular tumors arising after intradermal injection of immortalized murine endothelial cells were exposed to 50 to 150 J per cm2 of 690 nm laser light 15 min after intravenous injection of 1 mg per kg BPD. Tumor volume and gross response were followed after PDT-BPD and compared with control tumors receiving no treatment, light alone, or BPD alone. At 2 wk, hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling stained tumor sections was performed. There was a selective, fluence-dependent inhibition of tumor growth after PDT-BPD (p< or =0.05), typically with eradication of tumors exposed to higher fluences. A common effect was the replacement of tumor by small scar. Surrounding PDT-BPD exposed normal skin showed no changes. Based on these results, we conclude that PDT-BPD can lead to selective eradication of these tumors. Further studies investigating the efficacy of PDT-BPD for human hemangiomas are warranted.

Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin.

BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). METHODS: A total of 9 healthy participants of skin types II to III were exposed to varying doses of artificial UV radiation without and after oral administration of PL (7.5 mg/kg). At 24 hours after exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PL-treated and untreated skin. RESULTS: A significant decrease in erythema was found in PL-treated skin (P < .01). Histologically, PL-treated biopsy specimens showed less sunburn cells (P < .05), cyclobutane pyrimidine dimers (P < .001), proliferating epidermal cells (P < .001), and dermal mast cell infiltration (P < .05). A trend toward Langerhans cell preservation was seen. CONCLUSION: Oral administration of PL is an effective systemic chemophotoprotective agent leading to significant protection of skin against UV radiation.

Skin barrier in atopic dermatitis.

The skin represents the largest organ of the body and provides a vital interface between the body and the environment. Hereditary and acquired alterations of structural proteins and lipids of the stratum corneum and epidermal tight junctions leading to a diminished skin barrier function are major causative factors for a number of skin diseases, in particular atopic dermatitis (AD). This review summarizes current knowledge on the role of the skin barrier in AD with regard to pathogenesis and treatment, on the relationship between skin barrier abnormalities and immune aberrations, and on potential therapies aimed at repair of the skin barrier. Furthermore recent advances in the genetics of AD will be addressed.