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To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18–87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator’s Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response.

Background Steroid-sparing adjuvants may enhance oral glucocorticoid benefits in pemphigus treatment. Selecting the optimal therapeutic option among various first-line steroid-sparing adjuvants is often a clinical challenge due to the lack of head-to-head clinical trials. Objective To determine the best first-line steroid-sparing adjuvants for pemphigus treatment. Methods Randomized controlled trials comparing different steroid-sparing adjuvants in patients with pemphigus were identified through a systematic literature search and subjected to a network meta-analysis. The primary outcomes were the proportion of remission and the mean cumulative glucocorticoid dose. Results Ten trials involving 592 patients were analyzed. Among the 7 steroid-sparing adjuvants evaluated, rituximab was the most effective for achieving remission and was more effective than steroid alone (odds ratio, 14.35; 95% confidence interval [CI], 4.71-43.68). Rituximab, azathioprine, and cyclophosphamide pulse therapy enabled the reduction of the cumulative glucocorticoid doses compared to the use of steroid alone: mean differences, −11,830.5 mg (95% CI, −14,089.48 to −9571.52), −3032.48 mg (−4700.74 to −1364.22), and −2469.54 mg (−4128.42 to −810.66), respectively. Limitations The results were driven primarily by a small number of studies, and the effect estimates are imprecise because of indirect comparisons. Conclusion Network meta-analysis showed that rituximab appears to be an efficacious, well tolerated steroid-sparing adjuvant for pemphigus.

Limited studies on atopic dermatitis (AD) have investigated the possible covariance of sociodemographic factors with the Hospital Anxiety and Depression Scale (HADS).This study aimed to examine the possible covariance between AD severity and HADS scores of patients in Taiwan.Patients with AD from a medical center and 2 regional hospitals in Taiwan were enrolled in this cross-sectional study from April 2018 to April 2019. AD severity was measured using the "scoring atopic dermatitis" index, and anxiety and depression were screened based on HADS.A total of 200 patients were included. After correcting for sociodemographic variables, significantly more borderline (≥8) and abnormal (≥11) cases of anxiety/depression (First, the cross-sectional study design cannot show causality. Second, baseline data, including a history of underlying cancer or previous psychiatric disorder, were not obtained in the questionnaire and may confound the HADS scores. Finally, a standardized psychiatric clinical interviews study design should be used for higher accuracy in the assessment of psycho-comorbidities.Higher anxiety and depression risks were noted in patients with moderate-to-severe AD. Except for psychosomatic symptoms, all kinds of anxiety and depression symptoms occurred more frequently in patients with moderate-to-severe AD.

Atopic dermatitis has a substantial impact on work and activity impairment according to studies from Western communities. Prospective studies of work productivity and activity impairment in Asian patients with atopic dermatitis are lacking. The aims of this study were to investigate the impacts of atopic dermatitis on work productivity and activity impairment among Taiwanese patients, and to stratify the analyses by disease severity. One-third of employed participants reported missing work (absenteeism) in the preceding week due to atopic dermatitis, while 88.5% of the remaining two-thirds reported impaired work effectiveness (presenteeism). In addition, 92.5% of all participants reported impaired daily activities. Overall work impairment (aggregate productivity loss from absenteeism and presenteeism) was 1.8- and 2.6-fold greater in subjects with moderate and severe atopic dermatitis, respectively, compared with those with mild atopic dermatitis. Presenteeism, but not absenteeism, contributes to the majority of total work impairment in this cohort. Daily activity impairment was 1.5-fold greater in moderate atopic dermatitis, and 2.0-fold greater in severe atopic dermatitis, compared with mild atopic dermatitis. Both work and activity impairment showed significant positive correlations with atopic dermatitis severity scores (SCORing Atopic Dermatitis; SCORAD). In conclusion, work productivity and activity impairment is significantly correlated with disease severity in this Taiwanese atopic dermatitis cohort. In order to obtain a full picture of disease burden to patients and caregivers, patients with atopic dermatitis should be monitored for disease activity as well as corresponding impacts on quality of life.

Ming-Hsueh Tsai,1 Tom C Chan,2 Meng-Sui Lee,3,4 Mei-Shu Lai5 1Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan; 2Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 3Department of Dermatology, Taipei City Hospital, Taipei, Taiwan; 4Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Meng-Sui LeeDepartment of Dermatology, Taipei City Hospital, No. 33, Sec. 2, Zhonghua Road, Taipei, 100, TaiwanTel/Fax +886 2 23889595 Ext 2225Email leemengsui@hotmail.comMei-Shu LaiInstitute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 5Fl. No. 17, Hsu Chow Road, Taipei, 100, TaiwanTel +886 2 33668018Email mslai@ntu.edu.twPurpose: Psoriasis is an inflammatory disease associated with cardiovascular disease. Methotrexate (MTX) is a first-line systemic anti-psoriatic agent that may also protect against cardiovascular disease. We examined the cardiovascular risks among patients with psoriasis who were receiving MTX or the comparator, retinoids.Patients and Methods: We analysed data from the Taiwanese National Health Insurance database. The primary outcome was a composite of hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality (composite cardiovascular outcome). Propensity score-weighted analyses were used to evaluate patients who were followed from therapy initiation to the earliest instance of outcome occurrence, insurance disenrollment, death or study termination.Results: We identified 13,777 patients who received MTX and 6020 patients who received retinoids from 2000 to 2012. Compared to retinoids, MTX was associated with lower crude incidences of cardiovascular outcomes, hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality. In intention-to-treat analyses, MTX was associated with lower risks of composite cardiovascular outcomes (adjusted hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.76– 0.94), ischaemic heart disease (HR: 0.87, 95% CI: 0.71– 1.06), ischaemic stroke (HR: 1.06, 95% CI: 0.89– 1.27) and all-cause mortality (HR: 0.75, 95% CI: 0.66– 0.85). Similar results were found in as-treated analyses.Conclusion: In this nationwide cohort of patients with psoriasis, compared to retinoids, MTX was associated with a modestly lower risk of cardiovascular events.Keywords: cardiovascular events, inflammation, psoriasis, pharmacoepidemiology

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder. Recent clinical and basic research has demonstrated that AD is an immune-mediated disease involving multiple inflammatory pathways and is considered a T helper (TH)2-centered disease involving a common TH22 component. Recently, some reports demonstrated that Asian patients with AD are more likely to present with clearly demarcated lesions with prominent scaling and lichenification and may exhibit distinct immune and barrier features compared with European American patients with AD. Besides TH2 activation, patients of Asian descent (Japanese, Korean, and Chinese) with AD had strong TH17 activation, overlapping clinically and molecularly with some hallmarks of psoriasis.

Background/Purpose: Atopic dermatitis (AD) is a common skin disease. At present, there is little evidence regarding its impact on patients' health-related quality of life (HRQoL) in Taiwan. Therefore, this study investigated the relationship between AD severity and patients’ HRQoL in Taiwan. Methods: Patients with AD were recruited from three hospitals in Taiwan from April 2018 to April 2019. AD severity was measured using the Scoring of AD (SCORAD) scale, and HRQoL was assessed using the Dermatology Life Quality Index (DLQI) and the five-level version of EuroQol five-dimension questionnaire (EQ-5D-5L). Results: A total of 200 patients (mean age: 34.4 years) were recruited, including 103 males and 97 females. They were further classified as 79 mild, 72 moderate, and 58 severe AD patients according to their SCORAD scores. There was a positive correlation between their SCORAD and DLQI scores (Spearman's r = 0.77, p

Background/Purpose Atopic dermatitis (AD) is a chronic inflammatory disease commonly seen in children and increasingly recognized in adults. With recent advances in the therapeutic development for AD, the Taiwanese Dermatological Association (TDA) established a committee to update the consensus for AD management in Taiwan. This report describes the 2020 updated consensus for the management of AD. Methods A panel of 11 core members was convened to review and discuss aspects of AD management and draft recommendation during the first two meetings. The 2015 TDA consensus and the 2017 European guideline, along with recent peer-reviewed articles, serve as the foundation for the update. In the third meeting, AD expert dermatologists selected on a national scale were invited to vote on the final statements. A total of 27 dermatologists attended the final meeting. The consensus was achieved when ratings of 7–9 (out of a total score of 9) accounted for ≥ 75% of the total votes. Results Consensus was achieved on the therapeutic options for AD by lines of treatment. A treatment algorithm was presented to illustrate the place of each modality in terms of basic care, acute disease control, and maintenance therapy. Special considerations for the pediatric population, as well as for women during pregnancy and lactation, are discussed. Conclusion Topical corticosteroids with long-term emollient-based therapies remain the cornerstone of AD treatment. Systemic treatments are indicated when topical therapies and phototherapy fail to control the disease. The recent approval of dupilumab and emerging targeted therapies are expected to bring significant clinical benefit for patients whose disease is inadequately managed by existing options.

Psoriasis is one of the most common chronic inflammatory diseases that is characterized by well-defined erythematous plaques, with typical histopathological findings of lymphocytic infiltration and epidermal hyperplasia. Topical treatments of psoriasis are either associated with limited response or with side effects. Up to date, topicals targeting neuroimmune axis in psoriasis or psoriasiform dermatitis have not been explored. Here, we investigated whether percutaneous delivery of capsaicin could attenuate the pathological change of psoriasiform inflammation. Imiquimod-induced psoriasis-like murine model was used to evaluate therapeutic effects from topical application of capsaicin. An additional model of psoriasiform dermatitis induced by direct IL-23 injection was used to identify the level of action from capsaicin in this neuroimmune axis. Cutaneous inflammation was assessed by erythema level and ear thickness change. Key cytokines, infiltrating cells in the skin, and draining lymph node cells were investigated. The results showed that capsaicin administration obstructed the activation of IL-23/IL-17 pathway induced by imiquimod, presenting with significantly reduced psoriasiform dermatitis both in gross appearance and microscopic features. Tissue gene expression of psoriatic core cytokines induced by imiquimod (including IL-23, IL-17A, IL-22, TNF-α, and IL-6) were greatly decreased by capsaicin application. This protective effect from capsaicin could be hampered by direct intradermal injection of IL-23. Conclusion: Epicutaneous delivery of capsaicin on imiquimod-treated murine skin could significantly decrease expression of multiple inflammatory cytokines and the severity of prototypic change of psoriasiform inflammation. The beneficial effect imposed by capsaicin reinforces the neuroimmune contribution towards psoriasiform inflammation and provides a potential non-steroidal therapeutic alternative for topical treatment of psoriasiform dermatitis.

Psoriasis vulgaris is a common, heterogeneous, chronic inflammatory skin disease characterized by thickened, red, scaly plaques and systemic inflammation. Psoriasis is also associated with multiple comorbid conditions, such as joint destruction, cardiovascular disease, stroke, hypertension, metabolic syndrome, and chronic kidney disease. The discovery of IL-17–producing T cells in a mouse model of autoimmunity transformed our understanding of inflammation driven by T lymphocytes and associations with human inflammatory diseases, such as psoriasis. Under the regulation of IL-23, T cells that produce high levels of IL-17 create a self-amplifying, feed-forward inflammatory response in keratinocytes that drives the development of thickened skin lesions infiltrated with a mixture of inflammatory cell populations. Recently, the Food and Drug Administration approved multiple highly effective psoriasis therapies that disrupt IL-17 (secukinumab, ixekizumab, and brodalumab) and IL-23 (guselkumab and tildrakizumab) signaling in the skin, thus leading to a major paradigm shift in the way that psoriatic disease is managed.

African Americans (AA) are disproportionately impacted by atopic dermatitis (AD), with increased prevalence and therapeutic challenges unique to this population. Molecular profiling data informing development of targeted therapeutics for AD are derived primarily from European American (EA) patients. These studies are absent in AA, hindering development of effective treatments for this population.We sought to characterize the global molecular profile of AD in the skin of AA patients as compared with that of EA AD and healthy controls.We performed RNA-Seq with reverse transcription polymerase chain reaction validation and immunohistochemistry studies in lesional and nonlesional skin of AA and EA AD patients vs healthy controls.African American AD lesions were characterized by greater infiltration of dendritic cells (DCs) marked by the high-affinity immunoglobulin E (IgE) receptor (FcεR1+) compared with EA AD (P.05). Both AD cohorts showed similarly robust up-regulation of Th2-related (CCL17/18/26) and Th22-related markers (interleukin [IL]-22, S100A8/9/12), but AA AD featured decreased expression of innate immune (tumor necrosis factor [TNF], IL-1β), Th1-related (interferon gamma [IFN-γ], MX1, IL-12RB1), and Th17-related markers (IL-23p19, IL-36G, CXCL1) vs EA AD (P.05). The Th2 (IL-13) and Th22-related products (IL-22, S100A8/9/12) and serum IgE were significantly correlated with clinical severity (Scoring of Atopic Dermatitis [SCORAD]) in AA. Fillagrin (FLG) was exclusively down-regulated in EA AD, whereas loricrin (LOR) was down-regulated in both AD cohorts and negatively correlated with SCORAD in AA.The molecular phenotype of AA AD skin is characterized by attenuated Th1 and Th17 but similar Th2/Th22-skewing to EA AD. Our data encourages a personalized medicine approach accounting for phenotype-specific characteristics in future development of targeted therapeutics and clinical trial design for AD.

Beyond classic "allergic"/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-β) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis. Consistent with skin expression, AD serum showed up-regulation of Th2 (IL-13, CCL17, eotaxin-1/CCL11, CCL13, CCL4, IL-10), Th1 (CXCL10, CXCL11) and Th1/Th17/Th22 (IL-12/IL-23p40) responses. Surprisingly, some markers of atherosclerosis (fractalkine/CX3CL1, CCL8, M-CSF, HGF), T-cell development/activation (CD40L, IL-7, CCL25, IL-2RB, IL-15RA, CD6) and angiogenesis (VEGF-A) were significantly increased only in AD. Multiple inflammatory pathways showed stronger enrichment in AD than psoriasis. Several atherosclerosis mediators in serum (e.g. E-selectin, PI3/elafin, CCL7, IL-16) correlated with SCORAD, but not BMI. Also, AD inflammatory mediators (e.g. MMP12, IL-12/IL-23p40, CXCL9, CCL22, PI3/Elafin) correlated between blood and lesional as well as non-lesional skin. Overall, the AD blood signature was largely different compared to psoriasis, with dysregulation of inflammatory and cardiovascular risk markers, strongly supporting its systemic nature beyond atopic/allergic association.

Plaque psoriasis is one of the most common autoimmune skin diseases and is characterized by erythematous, scaly plaques. Many highly effective, targeted therapies have been developed as a result of an improved understanding of the pathogenesis of psoriasis. Using agents that target the central interleukin (IL)-23/IL-17 immune axis, this once difficult-to-treat disease is now among the most effectively treated autoimmune diseases with major clinical improvements possible in around 90% of patients. In this article, we outline the immune mechanisms responsible for the development of psoriasis and provide an overview of the novel IL-23 antagonists being used to manage this chronic skin disease.

Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, psoriasis autoantigens, and multiple environmental factors. Over the last two decades, research has unequivocally shown that psoriasis represents a bona fide T-cell mediated disease primarily driven by pathogenic T-cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/T17 cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition. The activation and upregulation of IL-17 in pre-psoriatic skin produces a “feed forward” inflammatory response in keratinocytes that is self-amplifying and drives the development of mature psoriatic plaques by inducing epidermal hyperplasia, epidermal cell proliferation, and the recruitment of leukocyte subsets into the skin. Clinical trial data for monoclonal antibodies against IL-17 signaling (secukinumab, ixekizumab, and brodalumab) and newer IL-23p19 antagonists (tildrakizumab, guselkumab, and risankizumab) underscore the central role of these cytokines as predominant drivers of psoriatic disease. We are currently witnessing a translational revolution in the treatment and management of psoriasis. Emerging bispecific antibodies offer the potential for even better disease control, while small molecule drugs may offer future alternatives to the use of biologics and less costly long-term disease management.

Beyond classic “allergic”/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-β) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis. Consistent with skin expression, AD serum showed up-regulation of Th2 (IL-13, CCL17, eotaxin-1/CCL11, CCL13, CCL4, IL-10), Th1 (CXCL10, CXCL11) and Th1/Th17/Th22 (IL-12/IL-23p40) responses. Surprisingly, some markers of atherosclerosis (fractalkine/CX3CL1, CCL8, M-CSF, HGF), T-cell development/activation (CD40L, IL-7, CCL25, IL-2RB, IL-15RA, CD6) and angiogenesis (VEGF-A) were significantly increased only in AD. Multiple inflammatory pathways showed stronger enrichment in AD than psoriasis. Several atherosclerosis mediators in serum (e.g. E-selectin, PI3/elafin, CCL7, IL-16) correlated with SCORAD, but not BMI. Also, AD inflammatory mediators (e.g. MMP12, IL-12/IL-23p40, CXCL9, CCL22, PI3/Elafin) correlated between blood and lesional as well as non-lesional skin. Overall, the AD blood signature was largely different compared to psoriasis, with dysregulation of inflammatory and cardiovascular risk markers, strongly supporting its systemic nature beyond atopic/allergic association.

Background African Americans (AA) are disproportionately impacted by atopic dermatitis (AD), with increased prevalence and therapeutic challenges unique to this population. Molecular profiling data informing development of targeted therapeutics for AD are derived primarily from European American (EA) patients. These studies are absent in AA, hindering development of effective treatments for this population. Objective We sought to characterize the global molecular profile of AD in the skin of AA patients as compared with that of EA AD and healthy controls. Methods We performed RNA-Seq with reverse transcription polymerase chain reaction validation and immunohistochemistry studies in lesional and nonlesional skin of AA and EA AD patients vs healthy controls. Results African American AD lesions were characterized by greater infiltration of dendritic cells (DCs) marked by the high-affinity immunoglobulin E (IgE) receptor (FceR1+) compared with EA AD (P Conclusion The molecular phenotype of AA AD skin is characterized by attenuated Th1 and Th17 but similar Th2/Th22-skewing to EA AD. Our data encourages a personalized medicine approach accounting for phenotype-specific characteristics in future development of targeted therapeutics and clinical trial design for AD.

Background Liver X receptors (LXRs) are involved in maintaining epidermal barrier and suppressing inflammatory responses in model systems. The LXR agonist VTP-38543 showed promising results in improving barrier function and inflammatory responses in model systems. Objective To assess the safety, tolerability, cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in adults with mild to moderate atopic dermatitis (AD). Methods A total of 104 ambulatory patients with mild to moderate AD were enrolled in this randomized, double-blind, vehicle-controlled trial between December 2015 and September 2016. VTP-38543 cream in 3 concentrations (0.05%, 0.15%, and 1.0%) or placebo was applied twice daily for 28 days. Pretreatment and posttreatment skin biopsy specimens were obtained from a subset of 33 patients. Changes in SCORing of Atopic Dermatitis, Eczema Area and Severity Index, Investigator's Global Assessment, and tissue biomarkers (by real-time polymerase chain reaction and immunostaining) were evaluated. Results Topical VTP-38543 was safe and well tolerated. VTP-38543 significantly increased messenger RNA (mRNA) expression of epidermal barrier differentiation (loricrin and filaggrin, P = .02) and lipid (adenosine triphosphate–binding cassette subfamily G member 1 and sterol regulatory element binding protein 1c, P H 17/T H 22-related (phosphatidylinositol 3, S100 calcium-binding protein A12) and innate immunity (interleukin 6) markers. Conclusion Topical VTP-38543 is safe and well tolerated. Its application led to improvement in barrier differentiation and lipids. Longer-term studies are needed to clarify whether a barrier-based approach can induce meaningful suppression of immune abnormalities. Trial Registration clinicaltrials.gov Identifier: NCT02655679.