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1.
Sci Transl Med ; 14(644): eabm8059, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35544596

RESUMO

Psoriasis is a widespread inflammatory skin disease affecting about 2% of the general population. Recently, treatments that specifically target key proinflammatory cytokines driving the disease have been developed to complement conventional therapies with unspecific antiproliferative or anti-inflammatory effects. Efficient monitoring of treatment efficacy in the context of precision medicine and the assessment of new therapeutics require accurate noninvasive readouts of disease progression. However, characterization of psoriasis treatment remains subjective based on visual and palpatory clinical assessment of features observed on the skin surface. We hypothesized that optoacoustic (photoacoustic) mesoscopy could offer label-free assessment of inflammation biomarkers, extracted from three-dimensional (3D) high-resolution images of the human skin, not attainable by other noninvasive methods. We developed a second-generation ultra-broadband optoacoustic mesoscopy system, featuring sub-10-µm resolution and advanced motion correction technology, and performed 80 longitudinal measurements of 20 psoriatic skin plaques in humans under conventional inpatient treatment or receiving biologics with concomitant topical corticosteroid treatment. Optoacoustic image analysis revealed inflammatory and morphological skin features that indicated treatment efficacy with sensitivity, accuracy, and precision that was not possible using clinical metrics. We identify 3D imaging biomarkers that reveal responses to treatment and offer the potential to facilitate disease and treatment characterization. Our findings suggest that optoacoustic mesoscopy may offer a method of choice for yielding both qualitative and quantitative evaluations of skin treatments that are inaccessible by other methods, potentially enabling optimized therapies and precision medicine in dermatology.

2.
Br J Dermatol ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35482474

RESUMO

BACKGROUND: Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice. OBJECTIVES: To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community. METHODS: A systematic search of CENTRAL, Embase, LILACS, and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving the psoriasis population (any age, n ≥50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any pre-specified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multi-stakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways. RESULTS: Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n=145) or psoriatic arthritis (n=30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. Candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, IL23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and Kallikrein 8 (proteomic), tyramine (metabolomic); PsA: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, Integrin b5, MMP-3 and M-CSF(proteomic) and tyramine and mucic acid (metabolomic) and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation. CONCLUSIONS: This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified here to expedite discovery and validation of biomarkers for clinical use.

4.
World Allergy Organ J ; 15(1): 100625, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35145605

RESUMO

BACKGROUND: Allergies have an enormous individual and economic impact worldwide and affect more than one quarter of the population in Germany. Various factors influence the development of allergies: besides genetic predisposition the environment in which a person is raised and living also plays a role. The aim of the study was to evaluate differences in allergy prevalence in relation to age, sex, occupation, and living area (settlement structures). METHODS: A cross-sectional study using a paper-based questionnaire about allergies was performed at the Munich Oktoberfest 2016. Participants were divided into 4 occupational groups and compared using descriptive statistics and multiple regression. RESULTS: Overall, 2701 individuals (mean age 51.9 ± 15.3 years; 53.5% women) participated in the study. The overall rate of any self-reported allergy was 27.3% in the study population, in which women were more likely to be affected than men (OR = 1.82; 95% CI [1.50; 2.22]). Compared to farmers, all other occupational groups had a higher risk of reporting pollen allergies. Participants from rural areas (OR = 0.38; 95% CI [0.26; 0.58]) and suburban areas (OR = 0.44; 95% CI [0.30; 0.64]) were significantly less affected by allergies than participants from urban areas. Around 45.2% of the participants affected by allergies reported not receiving any treatment at all. CONCLUSION: Differences in the self-reported prevalence of allergies were shown for age groups, sex, living area, and occupation. Especially the reported pollen allergy prevalence ranged widely between different occupations, indicating that those individuals with an occupational exposure to pollen may have a lower risk than indoor workers. Overall, there remains a high need for sufficient treatment of allergies.

5.
Am J Clin Dermatol ; 23(Suppl 1): 65-71, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35061229

RESUMO

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare disease characterized by episodic worsening (flares). Knowledge of the burden of GPP and the experience of affected individuals is limited. AIMS: To conduct a survey of people living with GPP to understand how they experience GPP flares, which therapies they have received and are receiving, and how GPP impacts their activities of daily living. METHODS: The online survey consisted of 43 questions answered by individuals recruited from an opt-in market research database. The research team performed a targeted outreach to identify individuals with GPP. The survey included screening questions to determine if potential participants qualified for inclusion. Eligible individuals were US residents aged ≥ 18 years who self-reported that they had been diagnosed with GPP. Respondents provided consent to participate and received compensation (fair market value) for their time. RESULTS: Between August 4 and 14, 2020, 66 people living with GPP in the USA were surveyed. Most participants were female, aged 40-59 years, had been diagnosed ≥ 1 year previously, and had experienced ≥ 2 flares in the past year. A substantial proportion of respondents had symptoms for years, had consulted multiple healthcare professionals, and experienced misdiagnoses before receiving a diagnosis of GPP. Emotional stress was the most common cause of flares and many respondents reported a fear of flares. Respondents defined flares by the presence of itching, an increase in the size of the affected area, more crusts or pustules, and fatigue. A change in mood was the most burdensome symptom. Most respondents were receiving topical corticosteroids and only approximately one-third felt their condition was well controlled. GPP had an impact on activities of daily living even in the absence of flares and many respondents felt that their physician did not understand the level of emotional, psychological, or physical pain caused by GPP. CONCLUSIONS: GPP imposes a substantial emotional burden on patients, with wide-ranging impacts on activities of daily living beyond the physical discomfort of skin lesions.


Assuntos
Psoríase/psicologia , Dermatopatias Vesiculobolhosas/psicologia , Atividades Cotidianas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Exacerbação dos Sintomas
6.
Am J Clin Dermatol ; 23(Suppl 1): 5-12, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35061224

RESUMO

Generalized pustular psoriasis (GPP) is a rare disease that has only recently benefited from a consistent definition and clinical coding standard. A lack of disease awareness combined with clinical similarities to other types of psoriasis have historically complicated the diagnosis of GPP. It is now clear that GPP requires a differential diagnosis from psoriasis vulgaris (plaque psoriasis), and better understanding of the genetic characteristics underlying GPP may improve the accuracy of diagnoses in the future. GPP can present at any age but is most common in the fifth decade of life. There appears to be a female preponderance in GPP, although there is notable variability in prevalence by geographical region and between ethnicities. GPP is potentially life-threatening, associated with several serious complications, and may require emergency treatment, particularly for complications arising from systemic inflammation. As with many rare diseases, there are inherent challenges to understanding the epidemiology of GPP. In addition to small patient numbers, estimating the prevalence of rare diseases is further complicated by studies that use non-standardized methodologies and that are conducted in different populations. These complications in data gathering have led to marked variability in GPP case estimates by geographical region and between ethnicities. There is ongoing research into disease characteristics, and insights into regional measures of prevalence are essential to increasing our understanding of GPP.


Assuntos
Psoríase/epidemiologia , Psoríase/patologia , Dermatopatias Vesiculobolhosas/epidemiologia , Dermatopatias Vesiculobolhosas/patologia , Diagnóstico Diferencial , Humanos , Prevalência , Fatores Sexuais
7.
J Invest Dermatol ; 142(1): 14-15, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34565563

RESUMO

IFN-1s are early sentinels of potential danger in skin. Two interconnected axes exist: plasmacytoid dendritic cells (DCs) secreting IFN-α in response to single strand RNA or DNA and keratinocytes secreting IFN-κ after stimulation with double strand RNA or other IFNs. Both IFN-α and IFN-κ induce macrophages and DC subpopulations to secrete master regulators of cytotoxicity or wound healing, the latter related to psoriasis pathogenesis.


Assuntos
Células Dendríticas , Psoríase , Humanos , Imunidade , Interferon-alfa , Pele
8.
Dermatol Ther (Heidelb) ; 12(1): 81-95, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34813044

RESUMO

INTRODUCTION: In the real-world APPRECIATE study (NCT02740218), most patients with psoriasis demonstrated notable improvements on disease severity measures and reported clinically meaningful treatment benefits with apremilast. OBJECTIVE: We aim to further describe patient-relevant needs and benefits and patient satisfaction with apremilast, including subgroup analyses based on patient characteristics. METHODS: APPRECIATE, a multinational, retrospective, cross-sectional study, enrolled patients with chronic plaque psoriasis who started apremilast according to the European label. Patient Benefit Index (PBI; range 0 (no patient-relevant benefit) to 4 (maximum patient-relevant benefit), global PBI score ≥ 1 indicating minimum patient-relevant benefit and ≥ 3 indicating high benefit) and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9; range 0-100) were assessed 6 (± 1) months after apremilast initiation and summarized descriptively. Relationships between global PBI and TSQM-9 assessments were analyzed by Pearson correlations. RESULTS: Of 480 enrolled patients, 347 (72.3%) had remained on apremilast at 6 (± 1) months; 90.9% (300/330) achieved global PBI score ≥ 1. Mean (standard deviation) global PBI score was 2.8 (1.2). Higher achievement of global PBI score ≥ 3 was observed in patients with no prior treatments (61.1% (22/36)) or prior phototherapy (64.6% (42/65)) versus prior conventional systemic (54.4% (100/184)) or biologic (38.6% (17/44)) treatment. Strong correlations were observed between the global PBI score and the TSQM-9 global satisfaction and effectiveness subscale scores. CONCLUSION: Patients continuing apremilast for 6 (± 1) months in APPRECIATE reported patient-relevant treatment benefits. Findings suggest that receiving apremilast earlier versus later in treatment management is consistent with greater improvements in patient-relevant treatment outcomes.

9.
J Invest Dermatol ; 142(3 Pt B): 804-810, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34538423

RESUMO

T cells are key drivers of autoimmunity in numerous noncommunicable inflammatory skin diseases by directly harming host tissue or through helping B cells in producing autoantibodies. Technological advances have contributed to identifying autoantigens, the Holy Grail of autoimmunity, in many inflammatory disorders of the skin. Novel therapeutic approaches such as chimeric (auto)antibody receptor T cells are a milestone on the way to finding individualized, well-tolerated, targeted therapies. This review summarizes the current knowledge on pathogenesis, immune response pattern‒related ontology, diagnostic approaches, and treatment options of autoimmune skin diseases.

10.
Allergy ; 77(1): 17-38, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34324716

RESUMO

Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and insufficient efficacy of classical drugs such as H1 R-antihistamines. Better understanding of the mechanisms has enabled a stratified approach to the management of CSU, supporting the use of targeted treatment with omalizumab. However, many practical issues including selection of responders, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness still require further clarification. The EAACI Guidelines on the use of omalizumab in CSU follow the GRADE approach in formulating recommendations for each outcome. In addition, future therapeutic approaches and perspectives as well as research priorities are discussed.


Assuntos
Antialérgicos , Produtos Biológicos , Urticária Crônica , Urticária , Adolescente , Adulto , Antialérgicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Criança , Doença Crônica , Humanos , Omalizumab/uso terapêutico , Resultado do Tratamento , Urticária/tratamento farmacológico
11.
J Dtsch Dermatol Ges ; 20(3): 287-295, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34962069

RESUMO

BACKGROUND AND OBJECTIVES: Molecular diagnostics (MDx) increasingly gains importance in dermatology and its application is a prerequisite for personalized medicine. The goal of this cross-sectional study was to determine how MDx is implemented in dermatologists' offices in the three fields of oncology, inflammation and infectiology and which hurdles office-based dermatologists face in terms of MDx. METHODS: Physician members of the Association of the German Dermatologists (Berufsverband der Deutschen Dermatologen e. V.; BVDD) were surveyed via an online questionnaire on MDx. RESULTS: 39.6 % of the 192 participants reported using MDx. Of these, the vast majority used MDx for diagnosing infectious diseases (86.5 % and 44.3 % of users perform MDx for detection of funghi and sexually transmitted diseases, respectively). Only a small minority applied MDx to answer oncological or immunological questions. The major obstacles for non-users as compared to users were difficulties in implementation, lack of expertise as well as time, personnel, and technical availability. Reimbursement was a main issue in both groups. CONCLUSIONS: Despite availability of specific therapies requiring precision medicine, MDx has not yet been broadly implemented in office-based dermatology. To advance MDx, more needs to be done in terms of continuous education, availability of reliable and valid tests, and reimbursability.


Assuntos
Dermatologia , Estudos Transversais , Alemanha , Humanos , Patologia Molecular , Inquéritos e Questionários
12.
Biomedicines ; 9(11)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34829927

RESUMO

(1) Background: Calcinosis cutis is a frequent symptom of autoimmune connective tissue diseases leading to pain, transcutaneous expulsion of calcified material and bacterial superinfection. There is a high need for new therapeutic options as no standardized treatment algorithm is established. While case reports indicate beneficial effects of bisphosphonates, standardized evaluation of treatment effects is missing. (2) Methods: In this retrospective analysis we evaluate the effects of intravenous pamidronate, a second-generation bisphosphonate, in seven patients with calcinosis cutis using consecutive clinical pictures, radiological examinations and patient's subjective evaluation. (3) Results: 5/6 patients reported a reduction of pain, improvement of general condition and cessation of calcinosis progression. Regression of skin lesions was detectable in clinical pictures of 2/6 patients, while 1/6 patients had stable disease. Radiological examination revealed improvement or stable disease in 3/5 patients. Fever was the most common side effect. One out of seven patients developed osteonecrosis of the jaw. (4) Conclusions: Bisphosphonates appear to have beneficial effects in a subgroup of calcinosis cutis patients. While patient's subjective evaluation was mainly positive, objective assessments showed improvement in approximately half of the cases. With regard to potential severe side effects, a careful risk-benefit evaluation is necessary before treatment initiation.

13.
BMJ Open ; 11(9): e049822, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518264

RESUMO

BACKGROUND: Guselkumab is an interleukin (IL)-23 pathway blocker with proven efficacy in patients with moderate-to-severe plaque psoriasis. Early intervention with guselkumab may result in changes to the clinical disease course versus later intervention. METHODS AND ANALYSIS: Here we present the rationale and design of a phase 3b, randomised, double-blind, multicentre study (GUIDE), comparing treatment effects of guselkumab in patients with short (≤2 years) or longer (>2 years) duration of plaque-type psoriasis, measured from first appearance of psoriatic plaques. Participants achieving skin clearance (Psoriasis Area and Severity Index (PASI)=0) by week 20 and maintaining complete clearance at week 28 visit ('super-responders' (SRe)) will be randomised to continue approved maintenance dosing every 8 weeks (q8w) versus an investigational maintenance dosing interval of 16 weeks (q16w) until week 68. Primary endpoint: proportion of participants in the q8w vs q16w arms with absolute PASI <3 at week 68. Participants with PASI <3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks. Participants not achieving SRe criteria (non-SRe) will remain in the study with q8w guselkumab dosing through week 68. Additional to serum samples obtained from all patients, skin biopsies and whole-blood samples will be taken from SRe and non-SRe participants at various time points in optional substudies. Analyses include: genetics; immunophenotyping (fluorescence-activated cell sorting); gene and protein expression profiling; immunohistology. By merging clinical endpoints with mechanistic findings, this study aims to elucidate how IL-23 blockade with guselkumab can modify the disease course by altering molecular and cellular drivers that cause relapse after treatment withdrawal, particularly among SRe. ETHICS AND DISSEMINATION: Approval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki. TRIAL REGISTRATION NUMBER: Registered at ClinicalTrials.gov (NCT03818035). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.


Assuntos
Interleucina-23 , Psoríase , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Humanos , Estudos Multicêntricos como Assunto , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Cells ; 10(8)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34440863

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. It is a multifactorial disease in which genetic and environmental factors play a key role. The primary defect in HS pathophysiology involves follicular occlusion of the folliculopilosebaceous unit, followed by follicular rupture and immune responses. Innate pro-inflammatory cytokines (e.g., IL-1ß, and TNF-α); mediators of activated T helper (Th)1 and Th17 cells (e.g., IFN-γ, and IL-17); and effector mechanisms of neutrophilic granulocytes, macrophages, and plasma cells are involved. On the other hand, HS lesions contain anti-inflammatory mediators (e.g., IL-10) and show limited activity of Th22 cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction, and scarring. HS pathogenesis is still enigmatic, and a valid animal model for HS is currently not available. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. Available treatments are limited, mostly off-label, and surgical interventions are often required to achieve remission. In this paper, we provide an overview of the current knowledge surrounding HS, including the diagnosis, pathogenesis, treatments, and existing translational studies.


Assuntos
Hidradenite Supurativa , Anti-Inflamatórios/uso terapêutico , Biomarcadores/metabolismo , Terapia Combinada , Citocinas/metabolismo , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/etiologia , Hidradenite Supurativa/patologia , Hidradenite Supurativa/terapia , Humanos , Inflamação , Pele/patologia
15.
JAMA Dermatol ; 157(9): 1047-1055, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34347860

RESUMO

IMPORTANCE: Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement. OBJECTIVE: To assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD. DESIGN, SETTING, AND PARTICIPANTS: Heads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy. The study was conducted from February 21, 2019, to December 9, 2020, at 129 centers located in 22 countries across Europe, North and South America, Oceania, and the Asia-Pacific region. Efficacy analyses were conducted in the intent-to-treat population. INTERVENTIONS: Patients were randomized 1:1 and treated with oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week. MAIN OUTCOMES AND MEASURES: The primary end point was achievement of 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16. Secondary end points were percentage change from baseline in the Worst Pruritus Numerical Rating Scale (NRS) (weekly average), proportion of patients achieving EASI100 and EASI90 at week 16, percentage change from baseline in Worst Pruritus NRS at week 4, proportion of patients achieving EASI75 at week 2, percentage change from baseline in Worst Pruritus NRS (weekly average) at week 1, and Worst Pruritus NRS (weekly average) improvement of 4 points or more at week 16. End points at week 24 included EASI75, EASI90, EASI100, and improvement of 4 points or more in Worst Pruritus NRS from baseline (weekly average). Safety was assessed as treatment-emergent adverse events in all patients receiving 1 or more dose of either drug. RESULTS: Of 924 patients screened, 348 (183 men [52.6%]; mean [SD] age, 36.6 [14.6] years) were randomized to receive upadacitinib and 344 were randomized to receive dupilumab (194 men [56.4%]; mean [SD] age, 36.9 [14.1] years); demographic and disease characteristics were balanced among treatment groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All ranked secondary end points also demonstrated the superiority of upadacitinib vs dupilumab, including improvement in Worst Pruritus NRS as early as week 1 (mean [SE], 31.4% [1.7%] vs 8.8% [1.8%]; P < .001), achievement of EASI75 as early as week 2 (152 [43.7%] vs 60 [17.4%]; P < .001), and achievement of EASI100 at week 16 (97 [27.9%] vs 26 [7.6%]; P < .001). Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for patients who received upadacitinib, whereas rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab. CONCLUSIONS AND RELEVANCE: During 16 weeks of treatment, upadacitinib demonstrated superior efficacy vs dupilumab in patients with moderate-to-severe AD, with no new safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03738397.


Assuntos
Dermatite Atópica , Eczema , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
16.
Exp Dermatol ; 30(10): 1517-1531, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34387406

RESUMO

The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time point for intervention are as yet unknown. The BIOMAP project is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome. The consortium includes 7 large pharmaceutical companies and 25 non-industry partners including academia. Since there is mounting evidence supporting an important role for microbial exposures and our microbiota as factors mediating immune polarization and AD and psoriasis pathogenesis, an entire work package is dedicated to the investigation of skin and gut microbiome linked to AD or psoriasis. The large collaborative BIOMAP project will enable the integration of patient cohorts, data and knowledge in unprecedented proportions. The project has a unique opportunity with a potential to bridge and fill the gaps between current problems and solutions. This review highlights the power and potential of the BIOMAP project in the investigation of microbe-host interplay in AD and psoriasis.


Assuntos
Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Microbiota/imunologia , Psoríase/imunologia , Psoríase/microbiologia , Pele/imunologia , Pele/microbiologia , Humanos
17.
Cells ; 10(7)2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206914

RESUMO

Whilst the importance of keratinocytes as a first-line defense has been widely investigated, little is known about their interactions with non-resident immune cells. In this study, the impact of human keratinocytes on T cell effector functions was analyzed in an antigen-specific in vitro model of allergic contact dermatitis (ACD) to nickel sulfate. Keratinocytes partially inhibited T cell proliferation and cytokine production. This effect was dependent on the keratinocyte/T cell ratio and was partially reversible by increasing the number of autologous dendritic cells. The inhibition of T cell proliferation by keratinocytes was independent of the T cell subtype and antigen presentation by different professional antigen-presenting cells. Autologous and heterologous keratinocytes showed comparable effects, while the fixation of keratinocytes with paraformaldehyde abrogated the immunosuppressive effect. The separation of keratinocytes and T cells by a transwell chamber, as well as a cell-free keratinocyte supernatant, inhibited T cell effector functions to the same amount as directly co-cultured keratinocytes, thus proving that soluble factor/s account for the observed suppressive effects. In conclusion, keratinocytes critically control the threshold of inflammatory processes in the skin by inhibiting T cell proliferation and cytokine production.


Assuntos
Inflamação/imunologia , Inflamação/patologia , Queratinócitos/patologia , Linfócitos T/imunologia , Apresentação do Antígeno/imunologia , Biomarcadores/metabolismo , Comunicação Celular , Proliferação de Células , Forma Celular , Microambiente Celular , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Queratinócitos/ultraestrutura , Modelos Biológicos , Pele/imunologia , Pele/patologia , Solubilidade , Linfócitos T/ultraestrutura
19.
Hautarzt ; 72(4): 354-357, 2021 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-33655344

RESUMO

A cohort of occupational dermatology patients will be set up at the University Hospital Heidelberg, Germany. In a 3-year prospective cohort study, the so-called molecular classifier will be applied in 262 patients to better differentiate between eczema and psoriasis. A retrospective cohort of 282 occupational health patients with the same suspected diagnosis but no molecular classifier designation was used as a control group. In 5 follow-up visits during 3 years, data will be obtained on diagnoses, disease course and severity, absence from work, occupation and quality of life. The research questions address whether early diagnoses will help to better identify the efficient treatment, disease course, absence from work and continuance of occupation. The study is sponsored by the public statutory employers' liability insurance (Deutsche Gesetzliche Unfallversicherung [DGUV]).


Assuntos
Dermatite Ocupacional , Eczema , Dermatoses da Mão , Psoríase , Estudos de Coortes , Eczema/diagnóstico , Eczema/genética , Seguimentos , Alemanha , Humanos , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/genética , Qualidade de Vida , Estudos Retrospectivos
20.
Allergy ; 76(4): 988-1009, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538044

RESUMO

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed.


Assuntos
Produtos Biológicos , Dermatite Atópica , Eczema , Adulto , Anticorpos Monoclonais Humanizados , Criança , Dermatite Atópica/tratamento farmacológico , Humanos
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