Author Correction: c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies.

Here we identify a group 2 innate lymphoid cell (ILC2) subpopulation that can convert into interleukin-17 (IL-17)-producing NKp44- ILC3-like cells. c-Kit and CCR6 define this ILC2 subpopulation that exhibits ILC3 features, including RORγt, enabling the conversion into IL-17-producing cells in response to IL-1ß and IL-23. We also report a role for transforming growth factor-ß in promoting the conversion of c-Kit- ILC2s into RORγt-expressing cells by inducing the upregulation of IL23R, CCR6 and KIT messenger RNA in these cells. This switch was dependent on RORγt and the downregulation of GATA-3. IL-4 was able to reverse this event, supporting a role for this cytokine in maintaining ILC2 identity. Notably, this plasticity has physiological relevance because a subset of RORγt+ ILC2s express the skin-homing receptor CCR10, and the frequencies of IL-17-producing ILC3s are increased at the expense of ILC2s within the lesional skin of patients with psoriasis.

Safety and efficacy of bimekizumab through 2 years in patients with moderate-to-severe plaque psoriasis: longer-term results from the BE SURE randomized controlled trial and the open-label extension from the BE BRIGHT trial.

BACKGROUND: BE SURE 1-year results demonstrated the superior efficacy of bimekizumab compared with adalimumab with no unexpected safety findings. OBJECTIVES: To provide efficacy and safety data over 2 years of bimekizumab treatment compared with adalimumab from BE SURE and the BE BRIGHT open-label extension (OLE) in patients with moderate-to-severe plaque psoriasis. METHODS: The 56-week double-blinded BE SURE phase III randomized controlled trial randomized patients 1 : 1 : 1 to bimekizumab 320 mg every 4 weeks (Q4W), bimekizumab 320 mg Q4W to week 16 then every 8 weeks (Q8W), or adalimumab 40 mg every 2 weeks to week 24 then bimekizumab 320 mg Q4W. After completing BE SURE, patients could enter the ongoing BE BRIGHT OLE, with possible dosing adjustments based on Psoriasis Area and Severity Index (PASI). The primary outcome in BE BRIGHT was incidence of treatment-emergent adverse events (TEAEs); safety data are reported by study period through week 104. Efficacy data are reported for the intention-to-treat population through week 104 by initial randomization group, with ≥ 90% improvement from baseline PASI (PASI 90) and 100% improvement (PASI 100) as key outcomes. RESULTS: Of the patients randomized to bimekizumab, 158 were assigned to Q4W, and 161 to Q4W/Q8W. At week 104, PASI 90 was achieved by 91.2% and 89.7%, and PASI 100 was achieved by 72.3% and 68.1%, for Q4W and Q4W/Q8W, respectively; comparable to week 16 results. Among the 159 patients randomized to adalimumab, responses rapidly and substantially increased after the week 24 bimekizumab switch; at week 104, 96.9% and 70.2% of patients achieved PASI 90 and PASI 100 respectively. Through weeks 24-104, the three most common TEAEs in any bimekizumab-treated group were nasopharyngitis, oral candidiasis and upper respiratory tract infection. Rates of serious TEAEs were low. CONCLUSIONS: Clinical responses observed through week 16 of BE SURE in patients randomized to bimekizumab were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Response rates were also sustained through week 104 in patients who switched from adalimumab to bimekizumab at week 24, and were similar to those observed in the bimekizumab groups. Bimekizumab was well tolerated with no new safety signals.

Enhanced topical cutaneous delivery of indocyanine green after various pretreatment regimens: comparison of fractional CO2 laser, fractional Er:YAG laser, microneedling, and radiofrequency.

Different devices have been used to enhance topical drug delivery. Aim of this study was to compare the efficacy of different skin pretreatment regimens in topical drug delivery. In six ex vivo human abdominal skin samples, test regions were pretreated with fractional CO2 and Er:YAG laser (both 70 and 300 µm ablation depth, density of 5%), microneedling (500 µm needle length), fractional radiofrequency (ablation depth of ± 80-90 µm), and no pretreatment. The fluorescent agent indocyanine green (ICG) was applied. After 3 h, fluorescence intensity was measured at several depths using fluorescence photography. Significantly higher surface fluorescence intensities were found for pretreatment with fractional Er:YAG and CO2 laser and for microneedling vs. no pretreatment (p < 0.05), but not for radiofrequency vs. no pretreatment (p = 0.173). Fluorescence intensity was highest for the Er:YAG laser with 300 µm ablation depth (mean 38.89 arbitrary units; AU), followed by microneedling (33.02 AU) and CO2 laser with 300 µm ablation depth (26.25 AU). Pretreatment with both lasers with 300 µm ablation depth gave higher fluorescence intensity than with 70 µm ablation depth (Er:YAG laser, 21.65; CO2 laser, 18.50 AU). Mean fluorescence intensity for radiofrequency was 15.27 AU. Results were comparable at 200 and 400 µm depth in the skin. Pretreatment of the skin with fractional CO2 laser, fractional Er:YAG laser, and microneedling is effective for topical ICG delivery, while fractional radiofrequency is not. Deeper laser ablation results in improved ICG delivery. These findings may be relevant for the delivery of other drugs with comparable molecular properties.

Drug penetration enhancement techniques in ablative fractional laser assisted cutaneous delivery of indocyanine green.

BACKGROUND AND OBJECTIVES: Topical drug delivery can be increased by pretreatment of the skin with ablative fractional laser (AFXL). Several physical penetration enhancement techniques have been investigated to further improve AFXL-assisted drug delivery. This study investigated the influence of three of these techniques, namely massage, acoustic pressure wave treatment, and pressure vacuum alterations (PVP) on the distribution of the fluorescent drug indocyanine green (ICG) at different depths in the skin after topical application on AFXL pretreated skin. MATERIALS AND METHODS: In ex vivo human skin, test regions were pretreated with AFXL (10,600 nm, channel depth 300 µm, channel width 120 µm, density 15%). Subsequently, ICG was applied, followed by massage, acoustic pressure wave treatment or PVP. ICG fluorescence intensity (FI) was assessed after 1, 3, and 24 hours at several depths using fluorescence photography. RESULTS: FI was higher when using enhancement techniques compared to control (AFXL-only) up to 3 hours application time (P < 0.05). After 3 hours, mean surface FI was highest after acoustic pressure wave treatment (61.5 arbitrary units; AU), followed by massage (57.5AU) and PVP (46.9AU), respectively (for comparison: AFXL-only 31.6AU, no pretreatment 14.9AU). Comparable or higher FI was achieved already after 1 hour with enhancement techniques compared to 3-24 hours application time without. After 24 hours, no significant differences between enhancement techniques and AFXL-only were observed (P = 0.31). CONCLUSION: Penetration enhancement techniques, especially acoustic pressure wave treatment and massage, result in improved drug accumulation in AFXL-pretreated skin and reduce the application time needed. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Parameters in fractional laser assisted delivery of topical anesthetics: Role of laser type and laser settings.

BACKGROUND AND OBJECTIVES: Efficacy of topical anesthetics can be enhanced by pretreatment of the skin with ablative fractional lasers. However, little is known about the role of parameters such as laser modality and laser density settings in this technique. Aims of this study were to compare the efficacy of pretreatment with two different ablative fractional laser modalities, a CO2 laser and an Er:YAG laser, and to assess the role of laser density in ablative fractional laser assisted topical anesthesia. STUDY DESIGN/MATERIALS AND METHODS: In each of 15 healthy subjects, four 10 × 10 mm test regions on the back were randomized to pretreatment (70-75 µm ablation depth) with CO2 laser at 5% density, CO2 laser at 15% density, Er:YAG laser at 5% density or Er:YAG laser at 15% density. Articaine hydrochloride 40 mg/ml + epinephrine 10 µg/ml solution was applied under occlusion to all four test regions. After 15 minutes, a pass with the CO2 laser (1,500 µm ablation depth) was administered as pain stimulus to each test region. A reference pain stimulus was given on unanesthetized skin. The main outcome parameter, pain, was scored on a 0-10 visual analogue scale (VAS) after each pain stimulus. RESULTS: Median VAS scores were 1.50 [CO2 5%], 0.50 [CO2 15%], 1.50 [Er:YAG 5%], 0.43 [Er:YAG 15%], and 4.50 [unanesthetized reference]. VAS scores for all pretreated test regions were significantly lower compared to the untreated reference region (P < 0.01). We found no significant difference in VAS scores between the CO2 and the Er:YAG laser pretreated regions. However, VAS scores were significantly lower at 15% density compared to 5% density for both for the CO2 laser (P < 0.05) and the Er:YAG laser (P < 0.01). Pretreatment with the CO2 laser was considered slightly more painful than pretreatment with Er:YAG laser by the subjects. CONCLUSION: Fractional laser assisted topical anesthesia is effective even with very low energy settings and an occlusion time of only 15 minutes. Both the CO2 laser and the Er:YAG laser can be used to assist topical anesthesia although the CO2 laser pretreatment is experienced as more painful. In our study settings, using articaine/epinephrine solution and an occlusion time of 15 minutes, a density of 15% was more effective than 5%. Lasers Surg. Med. 50:813-818, 2018. © 2018 Wiley Periodicals, Inc.

Discovery of skin lymphocytes was a game changer in experimental dermatology.

A substantial part of ongoing research in experimental dermatology focuses on skin T cells-for that reason, we find important to highlight the pioneering work of Jan D. Bos et al. from 1987 (The skin immune system (SIS): Distribution and immunophenotype of lymphocyte subpopulations in normal skin) https://www.ncbi.nlm.nih.gov/pubmed/3494791. This key article sets the record straight, once and for all, about the presence of lymphocytes in healthy skin, characterized the immunophenotypes of subpopulations, quantified these cells and studied their location. It was perhaps the critical discoveries made by Bos et al. that fuelled the scientific community's interest in skin lymphocytes, contributing to a new generation of cutaneous immunology research. We briefly describe additional scientific breakthroughs made since 1987. Nonetheless, the study of cutaneous lymphocytes remains essential to understand the relationship of these cells to human diseases and to develop therapies that can be leveraged to selectively mobilize, enhance or deplete these cells.

Patient-Reported Outcome Measurement in Clinical Dermatological Practice: Relevance and Feasibility of a Web-Based Portal.

BACKGROUND/AIMS: Patient-reported outcomes (PROs) are increasingly considered important. We developed a web-based application to electronically assess PROs in routine dermatological practice. We assessed (1) the relevance of PRO measurement according to health care providers and patients, (2) the feasibility of our application in routine practice according to health care providers, supporting staff and patients, and (3) barriers/facilitators for implementation according to health care providers and supporting staff. METHODS: Health care providers, supporting staff and patients completed study-specific questionnaires. Also, website statistics were analysed. RESULTS: 3/6 clinics participated, including 9 professionals and 80 patients. Both health care providers and patients rated PRO measurement as relevant. However, implementation was only moderately feasible. Time constraints and logistical problems were mentioned as barriers, and motivated patients and supportive staff as facilitators. CONCLUSION: Electronic PRO assessment in routine practice is not self-evident. Adjustments in logistics are recommended to optimize implementation, using a plan-do-study-act approach.

Fractional CO2 laser assisted delivery of topical anesthetics: A randomized controlled pilot study.

BACKGROUND AND OBJECTIVES: Many dermatological procedures are performed under local anesthesia. Topical anesthesia requires prolonged occlusion and is often insufficient. Infiltration anesthesia is associated with discomfort. Pretreatment with an ablative fractional laser (AFXL) may enhance penetration of topical drugs, including lidocaine. Primary aim of this study was to assess whether AFXL pretreatment enhances the efficacy of two regularly used anesthetics: (i) articain hydrochloride 40 mg/ml + epinephrine 10 µg/ml solution (AHES); (ii) lidocaine 25 mg/g + prilocaine 25 mg/g cream (EMLA cream). Secondary aim was to assess which anesthetic is superior on AFXL pretreated skin. MATERIALS AND METHODS: In 10 healthy subjects, four 1 cm(2) test regions on the back were randomized to [A] AFXL pretreatment (fractional CO2 laser, 5% density, 2.5 mJ/microbeam) + topical application of AHES, [B] AFXL pretreatment + EMLA cream, [C] sham AFXL + AHES, and [D] sham AFXL + EMLA cream. After ten minutes, an AFXL pass (35 mJ/microbeam) was given as pain stimulus at each test region. Pain was scored on a 0-10 visual analogue scale (VAS) after each stimulus. RESULTS: AFXL pretreatment was not considered painful. Median VAS scores for the pain stimulus were [A] 2.35, [B] 3.15, [C] 4.55, and [D] 4.35. VAS scores were significantly lower for region [A] (AFXL + AHES) versus region [B] (AFXL + EMLA; P < 0.01) and versus region [C] (sham AFXL + AHES; P < 0.01). VAS scores were not significantly different for region [B] (AFXL + EMLA) versus region [D] (sham AFXL + EMLA, P = 0.15). CONCLUSION: AFXL pretreatment at very low settings gives significant pain reduction already within ten minutes when AHES is used as topical anesthetic. AHES is clearly superior to EMLA cream on AFXL pretreated skin. Possibly, a liquid solution penetrates more easily into the AFXL channels than a cream. Further research should determine the clinical efficacy of laser assisted topical anesthesia and the exact role of the type of anesthetic, its vehicle and the laser settings.

Generalized eczematous reaction after fractional carbon dioxide laser therapy for tattoo allergy.

Allergic tattoo reactions form a therapeutically difficult entity. Treatment with conventional quality-switched lasers does not completely remove the allergenic particles and may lead to generalized hypersensitivity reactions. Recently, ablative fractional laser therapy was introduced as a treatment for allergic tattoo removal. We present two cases of allergic reactions to red tattoo ink treated with 10,600-nm fractional CO2 laser. At the end of treatment, almost complete removal of red ink accompanied by a significant reduction of symptoms was observed in the first patient, whereas the second patient developed an acute generalized eczematous reaction after five treatments. These findings confirm that ablative fractional laser therapy is capable of significant removal of tattoo ink in an allergic tattoo reaction. However, it implies a risk of generalized hypersensitivity reactions. To our knowledge, this is the first case of a generalized hypersensitivity reaction following treatment of tattoo allergy with the fractional CO2 laser.

Fractionated carbon dioxide laser therapy as treatment of mild rhinophyma: report of three cases.

Rhinophyma is a bothersome condition of the nose that is regarded as a manifestation of rosacea (subtype 3). Whereas the efficacy of medical treatments, including antibiotics and retinoids, is often dissatisfying, conventional invasive procedures are limited by their unfavorable side effect profile. We present three patients who were treated by a minimally invasive approach using fractionated carbon dioxide (CO2) laser therapy, showing variable response. We observed that fractionated CO2 laser therapy may improve patient-reported outcome in some patients with mild rhinophyma and is associated with a relatively favorable side effect profile compared with conventional surgical techniques.

A Web-based, educational, quality-of-life intervention for patients with a chronic skin disease: feasibility and acceptance in routine dermatological practice.

Chronic skin diseases have a negative impact on patients' health-related quality of life (HRQoL). Patient education might contribute to HRQoL improvement. We developed a web-based, educational, HRQoL intervention for patients with a chronic skin disease. We aimed to assess 1) the feasibility of implementing the intervention in routine dermatological practice and patients' daily life, and 2) the acceptance of the intervention by health care providers and patients. Additionally, we aimed to create a patient user profile. We conducted an observational pilot study at 6 dermatological centres, including 105 outpatients. Implementation in routine practice was feasible and acceptable to health care providers. However, implementation in patients' daily life was found not to be entirely feasible. Perceived relevance by patients was low, though patients rated the intervention as convenient and attractive. No univocal user profile was found. Suggestions for improvements of the intervention, e.g. tailoring and adding blended learning components, are discussed.

Elevating the Standard of Care for Patients with Psoriasis: 'Calls to Action' from Epicensus, a Multistakeholder Pan-European Initiative.

INTRODUCTION: Despite advances in treatment options and the management of patients with psoriasis, considerable unmet needs remain. Our objective was to identify ways to elevate the standard of care for patients with psoriasis by combining the perspectives of three important stakeholders: patients, clinicians and payors, and define 'Calls to Action' designed to achieve the identified changes. METHODS: Eight themes relevant to elevating the standard of care were identified from an insights-gathering questionnaire completed by all three stakeholder groups. A modified Delphi exercise gained consensus on statements informed by the insights. Statements were then used to inspire 'Calls to Action' - practical steps that could be taken to realise the desired changes and elevate the standard of care. RESULTS: In total, 18 European experts (10 dermatologists, 3 payors and 5 patient representatives) took part in the Delphi process. Consensus was reached on statements relating to all eight themes: improve healthcare systems to better support multidisciplinary team working and digital services, real-world data generation and optimal use, improve patient access, elevate quality-of-life measures as the most important outcomes, involve patients in patient-centred and personalised approaches to care, improve the relevance and reach of guidelines, education, and multistakeholder engagement. 'Calls to Action' common to all three stakeholder groups recognised the need to capitalise on the shift to digital healthcare, the need for consistent input into registries to generate real-world evidence to support guideline development, and the necessity of educating patients on the benefits of reporting outcomes to generate real-world data. The enormous quality-of-life burden and psychological impact of psoriasis, as well as the clinical needs of patients must be better understood, including by healthcare commissioners, so that funding priorities are assessed appropriately. CONCLUSION: This unique initiative identified a practical 'Call-to-Action Framework' which, if implemented, could help improve the standard of care for patients with psoriasis.

Despite improvements in the management of psoriasis, there is room for the standard of care for patients to be improved further. The aim of the 'Epicensus' programme is to help realise improvements by bringing together three important stakeholder groups involved in the care of patients with psoriasis: dermatologists, payors and patient representatives. First, unmet needs were explored with these stakeholders and eight themes for change were identified: 1) improve healthcare systems to better support multidisciplinary team working and digital services; 2) optimise real-world data generation and use; 3) improve patient access; 4) elevate quality-of-life measures as the most important outcomes; 5) involve patients in people-centred and personalised approaches to care; 6) improve the relevance and reach of guidelines; 7) education; 8) multistakeholder engagement. Next, a panel of experts representing the three stakeholder groups took part in a consensus process (Delphi) to reach agreement on statements relating to each of the eight themes. The statements describe current problems and what needs to be changed to raise the standard of care for patients with psoriasis. Some of the problems identified are similar to those that existed a decade ago, showing that simply recognising what needs to change is not enough to bring about improvements: action must be taken. Therefore, the Epicensus participants met to produce specific 'Calls to Action'­ practical steps described in this publication that, if put into practice, should contribute to an improvement in the standard of care for patients with psoriasis.

A cohort analysis of surgically treated primary head and neck lentigo maligna (melanoma): Prognostic value of melanoma subtype and new insights in the clinical value of guideline adherence.

BACKGROUND: Knowledge about lentigo maligna (melanoma) (LM/LMM) and its associated prognostic clinicopathological characteristics are limited compared to that of non-LM/LMM subtypes. The current study aimed to determine the clinical relevance of the LM/LMM subtype and its influence on recurrence and survival outcomes. METHODS: All consecutive cases of primary cutaneous head and neck LM/LMM treated by wide local excision over a ten-year period were retrospectively reviewed and compared to non-LM/LMM. Clinical outcome and prognostic factors were assessed by cumulative incidence and competing risk analyses. RESULTS: A total of 345 patients were identified. Specific clinicopathological characteristics such as lower median Breslow thickness (1.6 mm versus 2.1 mm; P = 0.013), association with diagnostic sampling errors (17.3% versus 5.2%; P = 0.01), and increased risk of local recurrences due to incomplete resection (18.7% versus 2.3%; P < 0.001), were significantly associated with LM/LMM. Guideline adherence was similar between the two study groups. The positive nodal status at baseline for LMM was low compared to non-LM/LMM (4.2% vs 17.9%; P = 0.037). The LMM subtype, facial localization, and reduced surgical margins (i.e., guideline non-adherence) were not shown to be independent prognostic factors for disease-free, melanoma-specific, or overall survival after correction for competing risks such as patient age and Breslow thickness. CONCLUSIONS: The LMM subtype was not shown to be prognostically different from non-LM/LMM when corrected for other variables of influence such as patient age and Breslow thickness. Reduced resection margins did not seem to affect disease-free, and melanoma-specific survival and warrant LM/LMM-specific guidelines. Further research is needed to evaluate the value of SLNB in LMM patients.

The use of specific antihypertensive medication and skin cancer risk: A systematic review of the literature and meta-analysis.

BACKGROUND: The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but photosensitivity has also been reported for other antihypertensive drugs. We conducted a systematic review and meta-analysis to compare skin cancer risk among antihypertensive drug classes and individual blood pressure lowering drugs. METHODS: We searched Medline, Embase, Cochrane and the Web of Science and included studies that investigated the association between antihypertensive medication exposure and non-melanoma skin cancer (NMSC) or cutaneous malignant melanoma (CMM). We combined the extracted odds ratios (OR) using a random effects model. RESULTS: We included 42 studies with a total of 16,670,045 subjects. Diuretics, in particular hydrochlorothiazide, were examined most frequently. Only 2 studies provided information about antihypertensive co-medication. Exposure to diuretics (OR 1.27 [1.09-1.47]) and calcium channel blockers (OR 1.06 [1.04-1.09]) was associated with an increased risk for NMSC. The increased risk for NMSC was only observed in case control studies and studies that did not correct for sun exposure, skin phototype or smoking. Studies that did correct for covariates as well as cohort studies did not show a significantly increased risk for NMSC. Egger's test revealed a significant publication bias for the subgroup of diuretics, hydrochlorothiazide and case-control studies concerning NMSC (p < 0.001). CONCLUSION: The available studies investigating the potential skin cancer risk that is associated with antihypertensive medication have significant shortcomings. Also, a significant publication bias is present. We found no increased skin cancer risk when analyzing cohort studies or studies that corrected for important covariates. (PROSPERO (CRD42020138908)).

The limited value of sentinel lymph node biopsy in lentigo maligna melanoma: A nomogram based on the results of 29 years of the nationwide dutch pathology registry (PALGA).

BACKGROUND: Lentigo maligna melanoma (LMM) predominantly presents in the head and neck of the elderly. The value of sentinel lymph node biopsy (SLNB) for LMM patients remains to be determined, as the reported average yield of positive lymph nodes is less than 10%. In this nationwide cohort study, we wanted to identify LMM patients with an increased risk of SLNB-positivity. METHODS: LMM with an SLNB indication according to the 8th AJCC melanoma guidelines were retrospectively identified from the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). A penalized (LASSO) logistic regression analysis was performed to determine the optimal combination of clinicopathological factors to predict a positive SLNB. RESULTS: Between 1991 and 2020, 1989 LMM patients met our inclusion criteria. SLNB was performed in 16.7% (n = 333) and was positive in 7.5% (25/333). The false-negative rate was 21.9%. Clinically detectable regional lymph node (LN) metastases were found in 1.3% (n = 25). Clinicopathological characteristics best predictive for SLNB-positivity (Odds ratio; 95% CI) were age (0.95; 0.91-0.99), ulceration 1.59 (0.44-4.83), T4-stage (1.81; 0.43-6.2), male sex (1.97; 0.79-5.27), (lymph)angioinvasion (5.07; 0.94-23.31), and microsatellites (7.23; 1.56-32.7) (C-statistic 0.75). During follow-up, regional LN recurrences were detected in 4.2% (83/1989) of patients, of which the majority (74/83) had no evidence of regional LN metastases at baseline. CONCLUSION: Our findings confirm the limited SLNB-positivity in LMM patients. Based on the identified high-risk clinicopathological features, a nomogram was developed to predict the risk of a positive SLNB.

A prospective, randomized, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: effects of adalimumab treatment on lesional and nonlesional skin.

BACKGROUND: There is a need for biomarkers to screen the effectiveness of (novel) therapeutic agents for psoriasis at an early stage. OBJECTIVE: We aimed to determine which of the changes in psoriatic skin correlates best with clinical improvement 4 weeks after effective adalimumab therapy. METHODS: Twenty-two psoriatic arthritis patients were randomized to receive adalimumab or placebo. T cell numbers and markers of innate immunity were estimated in lesional and nonlesional skin biopsies at baseline and after 4 weeks of treatment. RESULTS: CD161+ and elastase+ dermal cells in lesional skin were significantly reduced upon 4 weeks of successful adalimumab treatment compared with placebo. CONCLUSION: Early improvement of psoriasis lesions during adalimumab therapy is associated with a marked reduction of infiltrated dermal CD161+ T cells and elastase+ neutrophils, suggesting that these parameters could be used as biomarkers to monitor early changes after active treatment in small proof-of-concept studies of short duration.