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Psoriatic arthritis (PsA) is a complex inflammatory disease that challenges diagnosis and complicates the rational selection of effective therapies. Although T cells are considered active effectors in psoriasis and PsA, the role of CD8+ T cells in pathogenesis is not well understood. We selected the humanized mouse model NSG-SGM3 transgenic strain to examine psoriasis and PsA endotypes. Injection of PBMCs and sera from patients with psoriasis and PsA generated parallel skin and joint phenotypes in the recipient mouse. The transfer of human circulating memory T cells was followed by migration and accumulation in the skin and synovia of these immunodeficient mice. Unexpectedly, immunoglobulins were required for recapitulation of the clinical phenotype of psoriasiform lesions and PsA domains (dactylitis, enthesitis, bone erosion). Human CD8+ T cells expressing T-bet, IL-32 and CXCL14 were detected by spatial transcriptomics in murine synovia and by immunofluorescence in the human PsA synovia. Importantly, depletion of human CD8+ T cells prevented skin and synovial inflammation in mice humanized with PsA peripheral blood cells. The humanized model of psoriasis and PsA represents a valid platform for accelerating the understanding of disease pathogenesis, improving the design of personalized therapies, and revealing psoriatic disease targets.
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Artritis Psoriásica , Linfocitos T CD8-positivos , Modelos Animales de Enfermedad , Animales , Artritis Psoriásica/inmunología , Artritis Psoriásica/patología , Humanos , Ratones , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Ratones Transgénicos , Piel/patología , Piel/inmunología , Femenino , Masculino , Fenotipo , Psoriasis/inmunología , Psoriasis/patologíaRESUMEN
INTRODUCTION: Several classifications of psychodermatology disorders have been proposed, with most of them based on two to four main disorder category groups. However, there is, to date, no classification that has resulted from a consensus established by psychodermatology experts. The DSM-5-TR (Diagnostic and statistical manual of mental disorders (5th ed.), Text Revision) and the ICD-11 (International classification of diseases (11th revision)) also do not provide a systematized approach of psychodermatology disorders. Taking into consideration that classifications are a key pillar for a comprehensive approach to the pathologies of each branch of medicine, the proposal of a classification in psychodermatology appeared as a central need for the recognition of psychodermatological disorders, in an attempt to improve their recognition and, in that sense, to find a common language for the development of this subspecialty that crosses dermatology and psychiatry. METHODS: Previously published classifications in psychodermatology were critically reviewed and discussed by expert opinion from an international multidisciplinary panel of 16 experts in psychodermatology and a new classification system is proposed, considering classical concepts in general dermatology and psychopathology. RESULTS: Two main categories of disorders are presented (a main group related to primary mental health disorders and another main group related to primary skin disorders), which are subsequently subdivided into subgroups considering pathophysiological and phenomenological similarities, including key aspects of dermatological examination, namely the presence of visible skin lesions (primary and secondary skin lesions) and psychopathological correlates. CONCLUSION: This new classification aims to unify previous classifications, systematize the disorders that belong to psychodermatology and highlight their tenuous boundaries, to improve their management. It has been built and approved by the Psychodermatology Task Force of the European Academy of Dermatology and Venereology (EADV), the European Society for Dermatology and Psychiatry (ESDaP) and the Association for Psychoneurocutaneous Medicine of North America (APMNA).
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Dermatología , Trastornos Mentales , Enfermedades de la Piel , Humanos , Dermatología/métodos , Enfermedades de la Piel/complicaciones , Trastornos Mentales/psicología , Piel , PsicopatologíaRESUMEN
Chronic stress is an inextricable part of modern daily living; practically all human diseases, particularly cancer, are negatively affected by it. Numerous studies have shown that stressors, depression, social isolation, and adversity correlate with a worse prognosis for patients with cancer, with increased symptoms, early metastasis, and a shortened life span. Prolonged or very intense adverse life episodes are perceived and assessed by the brain and translated into physiologic responses mediated through relays to the hypothalamus and locus coereleus. This response triggers the activation of the hypothalamus-pituitary-adrenal axis (HPA) and the peripheral nervous system (PNS) with the secretion of glucocorticosteroids/epinephrine and norepinephrine (NE). These hormones and neurotransmitters affect immune surveillance and the immune response to malignancies by skewing immunity from a type 1 to a type 2 response; this process not only impedes the detection and killing of cancer cells but induces immune cells to facilitate cancer growth and systemic spread. It may be mediated by the engagement of norepinephrine to ß-adrenergic receptors, which can be partially reversed by the administration of ß-blockers.
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Neoplasias , Norepinefrina , Humanos , Epinefrina , Sistema Hipotálamo-Hipofisario , Estrés Psicológico/complicacionesRESUMEN
OBJECTIVE: The transition from psoriasis to psoriatic arthritis (PsA) occurs in 20-30% of patients; however, the mechanisms underlying the emergence of musculoskeletal disease are not well understood. Metabolic disease is prevalent in psoriasis patients, but whether metabolic factors, other than obesity, increase arthritis risk in psoriasis patients is not known. This study was undertaken to investigate the link between metabolic changes and disease progression in psoriasis patients. METHODS: To characterize the metabolic alterations during the progression of arthritis in psoriasis patients, we analyzed cross-sectional healthy controls and PsA samples and longitudinal psoriasis serum samples, before and after PsA onset. Nontargeted metabolomic profiling was performed using liquid chromatography mass spectrometry. RESULTS: We identified several serum metabolites that differed between PsA patients, psoriasis patients, and healthy controls. Differentially abundant bile acids, purines, pyrimidines, glutathione, lipids, and amino acid metabolites were noted in these 3 groups. We also noted differences between psoriasis patients who progressed and those who did not progress to PsA. Bile acid and butyrate levels were depressed in those who progressed to PsA compared to those who did not, and the level of inflammatory lipid mediators increased following PsA diagnosis. In particular, the combination of leukotriene B4 and glycoursodeoxycholic acid sulfate were sensitive and specific predictors of PsA progression. CONCLUSION: We observed notable differences in bile acid, purine, lipid, and amino acid-derived metabolites, among the healthy controls, psoriasis patients, and PsA patients and identified changes during the transition from psoriasis to PsA. The decreased bile acid and butyrate levels and elevated guanine levels in psoriasis patients at risk for PsA were particularly striking and may reflect gut microbial dysbiosis and dysregulated hepatic metabolism, leading to altered proliferation of immune cells and enhanced cytokine expression.
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Artritis Psoriásica , Psoriasis , Humanos , Artritis Psoriásica/diagnóstico , Ácidos y Sales Biliares , Nucleótidos , Estudios Transversales , Lípidos , AminoácidosRESUMEN
Although targeted immunomodulatory medications are increasingly utilized for inflammatory skin conditions like plaque psoriasis, little is known of the trends in the adoption of newly Federal Drug Administration (FDA)-approved immunomodulators by dermatologists. We performed a retrospective, cross-sectional analysis of Medicare Part D Prescriber datasets to identify dermatologists filing Medicare prescription claims for immunomodulatory drugs FDA-approved for plaque psoriasis between 2013 and 2018. Differences in dermatologist characteristics were determined between dermatologists prescribing a psoriasis treatment within two years of its FDA approval, "early adopters" and non-prescriber dermatologists over the same time period. Biologics approved for psoriasis from 2013 to 2018 included certolizumab pegol, secukinumab, brodalumab, ixekizumab, guselkumab, and apremilast. Early adopter dermatologists (n = 783) accounted for 5% of all Medicare Part D prescribing dermatologists. Early adopters were more likely to be male, in practice longer, and had a greater number of average annual beneficiaries than dermatologists who did not. Only six (< 1%) early adopters practiced in a small town or rural areas. We believe these data show that the adoption of novel biologic treatments for psoriasis by dermatologists to Medicare beneficiaries may be associated with clinician experience and practice volume. Additionally, we identified low absolute numbers of dermatologists prescribing biologics overall in non-metropolitan areas, which may represent delayed access to novel psoriasis treatments for many Medicare beneficiaries.
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Productos Biológicos , Medicare Part D , Psoriasis , Anciano , Humanos , Masculino , Estados Unidos , Femenino , Dermatólogos , Estudios Transversales , Estudios Retrospectivos , Factores Biológicos , Psoriasis/tratamiento farmacológico , Productos Biológicos/uso terapéutico , InmunomodulaciónRESUMEN
INTRODUCTION: Psoriatic arthritis (PsA) is a complex, immune-mediated disease associated with skin psoriasis that, if left untreated, can lead to joint destruction. Up to 30% of patients with psoriasis progress to PsA. In most cases, psoriasis precedes synovio-entheseal inflammation by an average of 5-7 years, providing a unique opportunity for early and potentially preventive intervention in a susceptible and identifiable population. Guselkumab is an effective IL-23p19 inhibitor Food and Drug Administration (FDA-approved for treatment of moderate-to-severe psoriasis and PsA. The Preventing Arthritis in a Multicentre Psoriasis At-Risk cohort (PAMPA) study aims to evaluate the efficacy of guselkumab in preventing PsA and decreasing musculoskeletal power Doppler ultrasound (PDUS) abnormalities in a population of patients with psoriasis who are at-increased risk for PsA progression. METHODS AND ANALYSIS: The PAMPA study is a multicentre, randomised, double-blind, placebo-controlled, interventional, preventive trial comparing PDUS involvement and conversion to PsA in patients with psoriasis at-increased risk for progression treated with guselkumab compared with non-biological standard of care. The study includes a screening period, a double-blind treatment period (24 weeks) and an open-label follow-up period (72 weeks). At baseline, 200 subjects will be randomised (1:1) to receive either guselkumab 100 mg (arm 1) or placebo switching to guselkumab 100 mg starting at week 24 (arm 2). Arm 3 will follow 150 at-risk psoriasis patients who decline biological therapy and randomisation. Changes from baseline in the PDUS score at week 24 and the difference in proportion of patients transitioning to PsA at 96 weeks will be examined as the coprimary endpoints. ETHICS AND DISSEMINATION: Ethics approval for this study was granted by the coordinating centre's (NYU School of Medicine) Institutional Review Board (IRB). Each participating site received approval through their own IRBs. The findings will be shared in peer-reviewed articles and scientific conference presentations. TRIAL REGISTRATION NUMBER: NCT05004727.
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Artritis Psoriásica , Psoriasis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Inhibidores de Interleucina , Resultado del Tratamiento , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Método Doble Ciego , Interleucina-23/uso terapéutico , Índice de Severidad de la Enfermedad , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
We present the first case of a patient with indolent polyarteritis nodosa who suffered severe exacerbations following significant emotional stressors. This report highlights the close relationship between emotions and autoimmune diseases mediated by the deleterious effects of stressors presumptively by skewing immunity from Type 1 to Type 2.
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Esquizofrenia , Escorbuto , Ácido Ascórbico , Hospitales , Humanos , Escorbuto/diagnósticoRESUMEN
Nevus sebaceus of Jadassohn, or "organoid nevus," is a common, benign hamartoma of the skin consisting of epithelial and adnexal components. Its natural history and association with neoplastic growths is well documented. The majority of concomitant neoplasms are benign-trichoblastoma and syringocystadenoma papilliferum are most frequently discovered-but malignant tumors have been described. We present the case of a 58-year-old male with a congenital nevus sebaceus of Jadassohn on his left parietal scalp that had been enlarging, changing color, and bleeding over the prior year. Clinical exam and histology disclosed the presence of a trichoblastoma and porocarcinoma arising within the nevus sebaceus. Porocarcinoma is a rare, intermediately aggressive, malignant eccrine gland tumor that is frequently metastasized at presentation. Otolaryngology performed wide local resection with sentinel lymph node biopsy. This case highlights the diversity of tumors associated with nevus sebaceus of Jadassohn, potential for malignant expansion, and necessity for close monitoring and maintaining a low threshold for biopsy in evolving lesions.
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This is an observational study demonstrating the effectiveness of pulsed dye laser (PDL) as a treatment of basal cell carcinomas (BCC) in patients with Gorlin Syndrome. Over 200 BCCs localized to the head, neck, trunk, and extremities of a patient suffering from Gorlin Syndrome were successfully treated with PDL without subsequent scarring. PDL is a simple and rapid modality to destroy BCCs arising in patients with Gorlin Syndrome resulting in a preferable cosmetic outcome.
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Síndrome del Nevo Basocelular , Láseres de Colorantes , Neoplasias Cutáneas , Carcinoma Basocelular , Síndrome de Hamartoma Múltiple , Humanos , Láseres de Colorantes/uso terapéutico , Neoplasias Cutáneas/radioterapia , Resultado del TratamientoRESUMEN
Patients that suffer from factitial dermatosis mutilate their skin, often lacking any consciousness of self-injury, attributing the resulting lesions to spontaneous development. The case hereby described shows how the health providers' interventions led a patient from a baseline undiagnosed factitious disorder to frank delusions of infestation with Mycobacterium Kansasii, and a relentless search for antibiotic treatments. We highlight the need for educating health practitioners on the characteristics of psycho-cutaneous disorders.
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Psoriasis is a chronic skin disease associated with considerable physical and psychological comorbidities. Stress and emotional disturbances have been implicated in both triggering the onset and exacerbation of psoriasis. In order to determine the level of perceived stress and mood alterations in patients with psoriasis and their association with disease severity, 300 individuals completed diverse validated questionnaires assessing stress and psychological mood. Evaluation of perception of disease was also measured. A significant association between psoriasis severity and mood, emotional disturbances and an impact on assessments of the quality of life were observed. Particularly, Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale and Hospital Anxiety and Depression Scale for Depression detected a significant risk for depression in relation to the disease severity. The association between depression features, anxiety and perceived stress with psoriasis severity is important and can influence the appropriate management of psoriasis.
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Ansiedad/psicología , Depresión/psicología , Emociones , Psoriasis/psicología , Estrés Psicológico/psicología , Adolescente , Adulto , Afecto , Anciano , Anciano de 80 o más Años , Ansiedad/diagnóstico , Ansiedad/epidemiología , Comorbilidad , Costo de Enfermedad , Depresión/diagnóstico , Depresión/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/diagnóstico , Psoriasis/epidemiología , Calidad de Vida , Factores de Riesgo , Índice de Severidad de la Enfermedad , España/epidemiología , Estrés Psicológico/diagnóstico , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios , Adulto JovenAsunto(s)
Carcinoma de Células Escamosas/cirugía , Herpes Zóster/etiología , Cirugía de Mohs/efectos adversos , Neoplasias Nasales/cirugía , Neoplasias Cutáneas/cirugía , Infección de la Herida Quirúrgica/etiología , Anciano de 80 o más Años , Antivirales/uso terapéutico , Femenino , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Humanos , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Valaciclovir/uso terapéuticoRESUMEN
Psoriasis is a chronic inflammatory disorder characterized by substantial psychiatric comorbidity. Historically, anecdotal observations have suggested that psychosocial distress can trigger flares of psoriasis, but over the past several decades, high-quality data from experimental studies support the assertion that stress plays a critical role in the pathogenesis of psoriasis. There may be a subset of patients unable to elicit an appropriate immunosuppressive response to stress through upregulation of cortisol, with resultant exacerbation of their psoriasis. Other notable studies revealed that key neuromodulators, including substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and nerve growth factor may be potent regulators of neurogenic inflammation that induce psoriasis flares through a stress-mediated mechanism. Preliminary trials in humans that examine psychosocial interventions to reduce stress, as well as animal studies targeting specific neuropeptides, provide support for the concept that alteration of pathways mediated by the stress response represents novel forms of therapy in the management of psoriasis.