RESUMO
Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.
Assuntos
Granuloma , Imunidade Inata , Receptores CXCR4 , Sarcoidose , Receptores CXCR4/imunologia , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Animais , Humanos , Camundongos , Sarcoidose/imunologia , Sarcoidose/patologia , Granuloma/imunologia , Granuloma/patologia , Dermatopatias/imunologia , Dermatopatias/patologia , Feminino , Quimiocina CXCL12/imunologia , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Pele/imunologia , Pele/patologia , Transdução de Sinais/imunologiaRESUMO
BACKGROUND: Systemic Lupus Erythematosus (SLE) has a strong genetic susceptibility, but little is known about the impact of diet on disease severity. The Western diet is typically deficient in magnesium (Mg), and given the immunomodulatory effects of Mg, we hypothesized that the low Mg intake increases disease risk and that increasing Mg intake would reduce severity of murine lupus. Here, we placed 12-week old MRL/lpr female lupus mice on a normal (Mg500) or a high (Mg2800) Mg diet for 9 weeks. Urine and blood were collected during the study for quantification of urinary albumin, BUN, anti-dsDNA antibodies, and immune phenotyping. RESULTS: MRL/lpr lupus mice on high Mg2800 diet had significantly fewer skin lesions and less severe skin histology score, and reduced levels of pathogenic anti-dsDNA antibodies, compared with the Mg500 group (143.8±75.0 vs. 47.4±36.2 × 106U/ml; P < 0.05). The high Mg2800 group had a nearly two-fold increase in the percentage of CD4+FOXP3+ Treg cells compared to controls (19.9±5.4 vs. 11.4±5.5%; P < 0.05). Treg percentages inversely correlated with the concentration of anti-dsDNA. None of the mice developed arthritis during the observation period and there were no significant differences in weight, proteinuria, BUN or kidney histology. CONCLUSION: In conclusion, oral supplementation of Mg has a protective effect in a murine lupus model and may represent an inexpensive and safe adjuvant in the treatment of SLsE.
Assuntos
Anticorpos Antinucleares , Lúpus Eritematoso Sistêmico , Magnésio , Linfócitos T Reguladores , Animais , Lúpus Eritematoso Sistêmico/imunologia , Feminino , Camundongos , Anticorpos Antinucleares/imunologia , Anticorpos Antinucleares/sangue , Magnésio/administração & dosagem , Linfócitos T Reguladores/imunologia , Modelos Animais de Doenças , Administração Oral , Camundongos Endogâmicos MRL lpr , Autoanticorpos/imunologia , Autoanticorpos/sangue , Pele/patologia , Pele/imunologia , Pele/efeitos dos fármacos , Dermatopatias/imunologia , Dermatopatias/tratamento farmacológico , Dermatopatias/patologiaRESUMO
BACKGROUND: An accurate diagnosis is the bedrock of the treatment of skin diseases. This study aimed to evaluate the correlation between clinical and pathological diagnosis of patients with skin disorders seen in dermatology units of Federal Medical Centre (FMC), Asaba, Delta State, and the University of Benin Teaching Hospital (UBTH), South-South Nigeria between 2019 - 2021. MATERIAL AND METHODS: This was a retrospective study of the charts of all patients seen in the dermatology units of FMC Asaba and UBTH who had skin biopsies for various skin diseases from 2019 to 2021. Biodata, clinical information, diagnosis, and histology results of these patients were collected using a questionnaire. One hundred and sixty-two (162) patients were excluded on account of the absence of a clinical diagnosis and a pathological conclusion of insufficient tissue sample. RESULTS: 356 skin biopsies were included. The male-to-female ratio was 1:1.18 and most patients were aged 40 to 49 years 74 (20.8%) with a mean age of 38.28± 19.19. Papulosquamous skin disorders accounted for 141 of the clinical diagnoses (39.0%) Among the histology request forms filled, only 69 (19.4% ) had detailed clinical history. Clinico-pathological concordance (CPC) was recorded in 214 (60.1%) cases and discordance in 142 (39.9%), both the highest concordance and discordance percentages were among papulosquamous diseases (45.1% and 31.5% respectively). There was no significant association between the completeness of documentation of patient's clinical information and clinicopathological concordance. CONCLUSION: Although the CPC was above 50% in this study, better modalities of communication between dermatologists and pathologists is desired.
CONTEXTE: Un diagnostic précis est la pierre angulaire du traitement des maladies de la peau. Cette étude visait à évaluer la corrélation entre le diagnostic clinique et le diagnostic pathologique chez les patients atteints de troubles cutanés observés dans les unités de dermatologie du Centre Médical Fédéral (FMC) d'Asaba, dans l'État du Delta, et de l'Hôpital Universitaire de Benin (UBTH), dans le sud-sud du Nigéria, entre 2019 et 2021. MATÉRIELS ET MÉTHODES: Il s'agit d'une étude rétrospective des dossiers de tous les patients vus dans les unités de dermatologie du FMC Asaba et de l'UBTH ayant subi des biopsies cutanées pour diverses maladies de la peau entre 2019 et 2021. Les données biodémographiques, les informations cliniques, les diagnostics et les résultats histologiques de ces patients ont été collectés à l'aide d'un questionnaire. Cent soixante-deux (162) patients ont été exclus en raison de l'absence d'un diagnostic clinique et d'une conclusion pathologique en raison d'échantillons de tissus insuffisants. RÉSULTATS: 356 biopsies cutanées ont été incluses. Le ratio hommes/femmes était de 1:1,18 et la plupart des patients avaient entre 40 et 49 ans, soit 74 (20,8%), avec un âge moyen de 38,28 ± 19,19 ans. Les troubles cutanés papulosquameux représentaient 141 des diagnostics cliniques (39,0%). Parmi les formulaires de demande d'histologie remplis, seuls 69 (19,4%) comportaient une histoire clinique détaillée. Une concordance clinico-pathologique (CPC) a été enregistrée dans 214 cas (60,1%) et une discordance dans 142 cas (39,9%), les pourcentages de concordance et de discordance les plus élevés étant enregistrés parmi les maladies papulosquameuses (45,1% et 31,5% respectivement). CONCLUSION: Bien que la CPC ait dépassé 50% dans cette étude, de meilleures modalités de communication entre les dermatologues et les pathologistes sont souhaitées.
Assuntos
Dermatopatias , Humanos , Nigéria/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatopatias/diagnóstico , Dermatopatias/patologia , Dermatopatias/epidemiologia , Biópsia/métodos , Biópsia/estatística & dados numéricos , Idoso , Adulto Jovem , Adolescente , Criança , Pele/patologia , Pré-EscolarAssuntos
Dermatologia , Dermatopatias , Humanos , Dermatopatias/diagnóstico , Dermatopatias/patologia , Dermatologia/história , AnimaisRESUMO
When dysregulated, skin fibrosis can lead to a multitude of pathologies. We provide a framework for understanding the wide clinical spectrum, mechanisms, and management of cutaneous fibrosis encompassing a variety of matrix disorders, fibrohistiocytic neoplasms, injury-induced scarring, and autoimmune scleroses. Underlying such entities are common mechanistic pathways that leverage morphogenic signaling, immune activation, and mechanotransduction to modulate fibroblast function. In light of the limited array of available treatments for cutaneous fibrosis, scientific insights have opened new therapeutic and investigative avenues for conditions that still lack effective interventions.
Assuntos
Fibrose , Dermatopatias , Pele , Humanos , Dermatopatias/patologia , Dermatopatias/terapia , Pele/patologia , AnimaisRESUMO
Particulate matter (PM) is a harmful air pollutant composed of chemicals and metals which affects human health by penetrating both the respiratory system and skin, causing oxidative stress and inflammation. This review investigates the association between PM and skin disease, focusing on the underlying molecular mechanisms and specific disease pathways involved. Studies have shown that PM exposure is positively associated with skin diseases such as atopic dermatitis, psoriasis, acne, and skin aging. PM-induced oxidative stress damages lipids, proteins, and DNA, impairing cellular functions and triggering inflammatory responses through pathways like aryl hydrocarbon receptor (AhR), NF-κB, and MAPK. This leads to increased production of inflammatory cytokines and exacerbates skin conditions. PM exposure exacerbates AD by triggering inflammation and barrier disruption. It disrupts keratinocyte differentiation and increases pro-inflammatory cytokines in psoriasis. In acne, it increases sebum production and inflammatory biomarkers. It accelerates skin aging by degrading ECM proteins and increasing MMP-1 and COX2. In conclusion, PM compromises skin health by penetrating skin barriers, inducing oxidative stress and inflammation through mechanisms like ROS generation and activation of key pathways, leading to cellular damage, apoptosis, and autophagy. This highlights the need for protective measures and targeted treatments to mitigate PM-induced skin damage.
Assuntos
Estresse Oxidativo , Material Particulado , Dermatopatias , Pele , Humanos , Material Particulado/efeitos adversos , Material Particulado/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Dermatopatias/metabolismo , Dermatopatias/patologia , Pele/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Animais , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/toxicidade , Inflamação/metabolismo , Envelhecimento da Pele/efeitos dos fármacosRESUMO
Many skin diseases begin with inflammatory changes on a molecular level. To develop a more thorough understanding of skin pathology and to identify new targets for therapeutic advancements, molecular mechanisms of inflammation in the context of skin disease should be studied. Current research efforts to better understand skin disease have focused on examining the role of molecular processes at several stages of the inflammatory response such as the dysregulation of innate immunity sensors, disruption of both transcriptional and post-transcriptional regulation, and crosstalk between immune and neuronal processes (neuro-immune crosstalk). This review seeks to summarize recent developments in our understanding of inflammatory processes in skin disease and to highlight opportunities for therapeutic advancements. With a focus on publications within the past 5 years (2019-2024), the databases PubMed and EBSCOhost were used to search for peer-reviewed papers regarding inflammatory molecular mechanisms and skin disease. Several themes of research interest regarding inflammatory processes in skin disease were determined through extensive review and were included based on their relative representation in current research and their focus on therapeutic potential. Several skin diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and scleroderma were described in the paper to demonstrate the widespread influence of inflammation in skin disease.
Assuntos
Inflamação , Dermatopatias , Humanos , Inflamação/patologia , Dermatopatias/patologia , Dermatopatias/imunologia , Dermatopatias/etiologia , Dermatopatias/metabolismo , Animais , Imunidade Inata , Pele/patologia , Pele/metabolismo , Pele/imunologia , Dermatite Atópica/patologia , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite Atópica/genética , Dermatite Atópica/etiologia , Psoríase/patologia , Psoríase/genética , Psoríase/metabolismo , Psoríase/imunologia , Psoríase/etiologiaRESUMO
BACKGROUND: Xanthomas are papulo-nodular, yellow, soft, painless, dermal-based non-neoplastic cutaneous lesions that comprise of localized aggregates of lipid-laden histiocytes. CASE REPORT: A thirteen-year-old adolescent girl presented with multiple, large, bilateral, nodules present over elbows, posterior aspect of heel, and knees for five years. Fine needle aspiration cytology was performed, and the smears showed numerous foamy histiocytes, a few benign spindle cells, and foreign-body giant cells against a lipidaceous background. Her maternal aunt and grandmother also had xanthelasma palpebrarum. Serum lipid levels were advised and were markedly deranged in all three of them. Based on the corroborative clinical, biochemical, and cytopathological findings, a final diagnosis of familial hypercholesterolemia (FH) was rendered. CONCLUSION: The present case sheds light on the importance of prompt cytopathological diagnosis of xanthomatous lesions, especially in children and adolescents, as it can help prevent morbidity and mortality due to associated premature adverse cardiovascular and cerebrovascular events if left undiagnosed.
Assuntos
Hiperlipoproteinemia Tipo II , Xantomatose , Humanos , Feminino , Adolescente , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/patologia , Xantomatose/diagnóstico , Xantomatose/patologia , Dermatopatias/diagnóstico , Dermatopatias/patologia , Biópsia por Agulha Fina , Pele/patologiaAssuntos
Doença Relacionada a Imunoglobulina G4 , Plasmócitos , Humanos , Plasmócitos/patologia , Plasmócitos/imunologia , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/patologia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Masculino , Dermatopatias/patologia , Dermatopatias/imunologia , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
This study aims to explore the efficacy of a hybrid deep learning and radiomics approach, supplemented with patient metadata, in the noninvasive dermoscopic imaging-based diagnosis of skin lesions. We analyzed dermoscopic images from the International Skin Imaging Collaboration (ISIC) dataset, spanning 2016-2020, encompassing a variety of skin lesions. Our approach integrates deep learning with a comprehensive radiomics analysis, utilizing a vast array of quantitative image features to precisely quantify skin lesion patterns. The dataset includes cases of three, four, and eight different skin lesion types. Our methodology was benchmarked against seven classification methods from the ISIC 2020 challenge and prior research using a binary decision framework. The proposed hybrid model demonstrated superior performance in distinguishing benign from malignant lesions, achieving area under the receiver operating characteristic curve (AUROC) scores of 99%, 95%, and 96%, and multiclass decoding AUROCs of 98.5%, 94.9%, and 96.4%, with sensitivities of 97.6%, 93.9%, and 96.0% and specificities of 98.4%, 96.7%, and 96.9% in the internal ISIC 2018 challenge, as well as in the external Jinan and Longhua datasets, respectively. Our findings suggest that the integration of radiomics and deep learning, utilizing dermoscopic images, effectively captures the heterogeneity and pattern expression of skin lesions.
Assuntos
Aprendizado Profundo , Dermoscopia , Humanos , Dermoscopia/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Curva ROC , Pele/diagnóstico por imagem , Pele/patologia , Processamento de Imagem Assistida por Computador/métodos , Dermatopatias/diagnóstico por imagem , Dermatopatias/patologia , Interpretação de Imagem Assistida por Computador/métodos , RadiômicaAssuntos
Calcinose , Quelantes , Humanos , Calcinose/induzido quimicamente , Calcinose/patologia , Quelantes/uso terapêutico , Quelantes/efeitos adversos , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Dermatopatias/induzido quimicamente , Dermatopatias/patologia , Masculino , Feminino , Calcinose CutâneaRESUMO
Tissues are organized into anatomical and functional units at different scales. New technologies for high-dimensional molecular profiling in situ have enabled the characterization of structure-function relationships in increasing molecular detail. However, it remains a challenge to consistently identify key functional units across experiments, tissues, and disease contexts, a task that demands extensive manual annotation. Here, we present spatial cellular graph partitioning (SCGP), a flexible method for the unsupervised annotation of tissue structures. We further present a reference-query extension pipeline, SCGP-Extension, that generalizes reference tissue structure labels to previously unseen samples, performing data integration and tissue structure discovery. Our experiments demonstrate reliable, robust partitioning of spatial data in a wide variety of contexts and best-in-class accuracy in identifying expertly annotated structures. Downstream analysis on SCGP-identified tissue structures reveals disease-relevant insights regarding diabetic kidney disease, skin disorder, and neoplastic diseases, underscoring its potential to drive biological insight and discovery from spatial datasets.
Assuntos
Biologia Computacional , Humanos , Animais , Biologia Computacional/métodos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Camundongos , Dermatopatias/genética , Dermatopatias/patologiaRESUMO
Calcinosis cutis is classified into 5 main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. However, it is occasionally misdiagnosed as a malignancy and its management remains challenging. Therefore, in this study, we report our diagnostic and treatment experiences with patients with calcinosis cutis and suggest strategies for improving patient care. This retrospective study included 7 patients (4 men, 3 women; 44.4â ±â 32.0 years old) who visited our hospital between March 2013 and December 2022 and were diagnosed with calcinosis cutis through histopathological procedures. The patients underwent complete excision of the mass without a safety margin. Frozen biopsy was not performed during surgery. No significant intraoperative or postoperative complications were noted after the application of various imaging techniques for diagnosis and follow-up. All patients showed complete recovery. Follow-up showed no recurrence or complications in the 6 patients who completed 1 year of follow-up. Radiological tests such as plain radiography, ultrasonography, computed tomography, and magnetic resonance imaging are important for accurate diagnosis and treatment of calcinosis cutis. This approach can ensure precise assessment of preoperative lesions, leading to safe and less invasive patient treatment, recurrence prevention, and complications of calcinosis cutis.
Assuntos
Calcinose , Dermatopatias , Humanos , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Dermatopatias/diagnóstico , Dermatopatias/patologia , Dermatopatias/cirurgia , Calcinose CutâneaRESUMO
The assessment of free-ranging cetacean health through the study of skin conditions using photographs has gained prominence in recent years. However, little attention has been given to the relationships between cetacean skin conditions, species, and body condition. To explore this relationship among baleen whale species along the northwestern coast of Spain, we employed a non-invasive method involving photograph analysis. In this study, we examined skin conditions (including injuries, epizoites and ectoparasites, pigmentation disorders, skin lesions, and anatomical malformations) and body condition (overall physical contours and form, as an indicator of nutritional status and health) in 3 species of whales (blue, fin, and minke whales). This methodology facilitated the identification of 29 subcategories of distinct skin conditions and an assessment of body condition over a 5 yr period (2017 to 2021). In our study, we present evidence linking hypopigmentation, protruding pieces of tissue, and tattoo-like lesions to 'Poor' body condition in the 3 baleen whale species. Fin whales exhibited a higher susceptibility to mottling (prevalence = 17.7%), while blue whales were more prone to starbursts (prevalence = 90.5%). Additionally, we found a significant relationship between skin condition diversity and individual body condition. Our findings contribute valuable information to the broader understanding of the health status of baleen whales. Further investigations are necessary to delve into the etiology of the documented skin conditions and their potential implications for individual survival. This study serves as a foundation for ongoing research aimed at advancing our comprehension of these findings.
Assuntos
Baleias , Animais , Pele , Especificidade da Espécie , Dermatopatias/veterinária , Dermatopatias/epidemiologia , Dermatopatias/patologia , Espanha/epidemiologiaRESUMO
BACKGROUND: Laser technology is a viable therapeutic option for treating a number of skin pathologic conditions, including pigmented lesions, vascular lesions and acne scars. AIM: In this work, through in vitro and clinical investigations we test the efficacy, the safety and the speed of treatment of high-powered laser system emitting a 675-nm in the management of various skin condition. MATERIALS AND METHODS: In vitro experiments were performed irradiating adult human dermal fibroblasts cells (HDFa) with 675-nm laser for 24, 48 and 72 h with different fluences and Ki-67+ cells were counted. The confocal microscopy images of control and treated samples were acquired. Clinical skin rejuvenation/diseases treatments with 675 nm laser device were performed with different laser parameters in 11 patients with pigmented lesions, 5 patients with acne scars and 23 patients for skin rejuvenation. Data were evaluated with the validated global score using 5-point scales (GAIS) and patient's satisfaction scale. RESULTS: The application of the high-power 675 nm laser has proven effective in stimulating cell proliferation in in vitro experiments and it led to good results for all skin pathologies. GAIS showed values between 3 and 4 points for all treated pathologies, all scores between '75%-good improvements' and '100%-excellent improvements'. The treatment time was reduced by 50% compared to the old parameters setting, resulting in a faster and good patient's satisfying technique. No serious adverse effects were recorded. CONCLUSION: the preclinical and clinical data confirm the efficacy and safety of this high-powered 675 nm laser for several skin condition.
Assuntos
Fibroblastos , Rejuvenescimento , Humanos , Adulto , Feminino , Fibroblastos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Dermatopatias/radioterapia , Dermatopatias/patologia , Proliferação de Células , Resultado do Tratamento , Células Cultivadas , Satisfação do Paciente , Terapia a Laser/métodos , Terapia a Laser/instrumentação , Pele/patologia , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação , Acne Vulgar/radioterapia , Acne Vulgar/patologia , Acne Vulgar/complicações , Cicatriz/patologia , Adulto JovemRESUMO
Inflammatory skin conditions highly influence the quality of life of the patients suffering from these disorders. Symptoms include red, itchy and painful skin lesions, which are visible to the rest of the world, causing stigmatization and a significantly lower mental health of the patients. Treatment options are often unsatisfactory, as they suffer from either low patient adherence or the risk of severe side effects. Considering this, there is a need for new treatments, and notably of new ways of delivering the drugs. Stimuli-responsive drug delivery systems are able to deliver their drug cargo in response to a given stimulus and are, thus, promising for the treatment of inflammatory skin conditions. For example, the use of external stimuli such as ultraviolet light, near infrared radiation, or alteration of magnetic field enables drug release to be precisely controlled in space and time. On the other hand, internal stimuli induced by the pathological condition, including pH alteration in the skin or upregulation of reactive oxygen species or enzymes, can be utilized to create drug delivery systems that specifically target the diseased skin to achieve a better efficacy and safety. In the latter context, however, it is of key importance to match the trigger mechanism of the drug delivery system to the actual pathological features of the specific skin condition. Hence, the focus of this article is placed not only on reviewing stimuli-responsive drug delivery systems developed to treat specific inflammatory skin conditions, but also on critically evaluating their efficacy in the context of specific skin diseases. STATEMENT OF SIGNIFICANCE: Skin diseases affect one-third of the world's population, significantly lowering the quality of life of the patients, who deal with symptoms such as painful and itchy skin lesions, as well as stigmatization due to the visibility of their symptoms. Current treatments for inflammatory skin conditions are often hampered by low patient adherence or serious drug side effects. Therefore, more emphasis should be placed on developing innovative formulations that provide better efficacy and safety for patients. Stimuli-responsive drug delivery systems hold considerable promise in this regard, as they can deliver their cargo precisely where and when it is needed, reducing adverse effects and potentially offering better treatment outcomes.