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BACKGROUND: Artificial intelligence (AI) is reshaping healthcare, using machine and deep learning (DL) to enhance disease management. Dermatology has seen improved diagnostics, particularly in skin cancer detection, through the integration of AI. However, the potential of AI in automating immunofluorescence imaging for autoimmune bullous skin diseases (AIBDs) remains untapped. While direct immunofluorescence (DIF) supports diagnosis, its manual interpretation can hinder efficiency. The use of DL to classify DIF patterns automatically, including the intercellular (ICP) and linear pattern (LP), holds promise for improving the diagnosis of AIBDs. OBJECTIVES: To develop AI algorithms for automated classification of AIBD DIF patterns, such as ICP and LP, in order to enhance diagnostic accuracy, streamline disease management and improve patient outcomes through DL-driven immunofluorescence interpretation. METHODS: We collected immunofluorescence images from skin biopsies of patients suspected of having an AIBD between January 2022 and January 2024. Skin tissue was obtained via a 5-mm punch biopsy, prepared for DIF. Experienced dermatologists classified the images as ICP, LP or negative. To evaluate our DL approach, we divided the images into training (n = 436) and test sets (n = 93). We employed transfer learning with pretrained deep neural networks and conducted fivefold cross-validation to assess model performance. Our dataset's class imbalance was addressed using weighted loss and data augmentation strategies. The models were trained for 50 epochs using Pytorch, achieving an image size of 224 × 224 pixels for both convolutional neural networks (CNNs) and the Swin Transformer. RESULTS: Our study compared six CNNs and the Swin Transformer for AIBD image classification, with the Swin Transformer achieving the highest average validation accuracy (98.5%). On a separate test set, the best model attained an accuracy of 94.6%, demonstrating 95.3% sensitivity and 97.5% specificity across AIBD classes. Visualization with Grad-CAM (class activation mapping) highlighted the model's reliance on characteristic patterns for accurate classification. CONCLUSIONS: The study highlighted the accuracy of CNNs in identifying DIF features. This approach aids automated analysis and reporting, offering reproducibility, speed, data handling and cost-efficiency. Integrating DL into skin immunofluorescence promises precise diagnostics and streamlined reporting in this branch of dermatology.
Artificial intelligence (AI) is transforming healthcare through machine and deep learning (computer systems that can learn and adapt, and make complex decisions, without receiving explicit instructions), improving disease management in dermatology, particularly in detecting skin cancer. However, AI's potential in automating immunofluorescence imaging in autoimmune bullous (blistering) skin diseases (AIBDs) remains largely untapped. Manual interpretation of direct immunofluorescence (DIF a type of microscopy) can reduce efficiency. However, using deep learning to automatically classify DIF patterns (for example, the 'intercellular pattern' (ICP) and the 'linear pattern' (LP)) holds promise in helping with the diagnosis of AIBDs. This study aimed to develop AI algorithms for the automated classification of AIBD DIF patterns, such as ICP and LP, to improve diagnostic accuracy and streamline disease management. Immunofluorescence images were collected from skin biopsies of patients with a suspected AIBD between January 2022 and January 2024. Dermatologists classified the images into three categories: ICP, LP and negative. The dataset was divided into training (436 images) and test sets (93 images). A transfer learning framework (where what has been learned previously in one setting is used to improve performance in another) was used to make up for the limited amount of training data, to explore different models for the AIBD classification task. Our results revealed that a model called the 'Swin Transformer' achieved an average accuracy of 99% in diagnosing different AIBDs. The best model attained 95% accuracy on the test set and was reliable in identifying and ruling out different AIBDs. Visualization with Grad-CAM (a technique used in deep learning) highlighted the model's use of characteristic patterns to classify the diseases accurately. Overall, integrating deep learning in skin immunofluorescence promises to improve diagnostics and streamline reporting in dermatology, which could improve consistency, speed and cost-efficiency.
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Doenças Autoimunes , Aprendizado Profundo , Dermatopatias Vesiculobolhosas , Humanos , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/patologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Técnica Direta de Fluorescência para Anticorpo/métodos , Pele/patologia , Pele/imunologia , Biópsia , AlgoritmosRESUMO
BACKGROUND: Trypanophobia or "needle phobia" represents a potential hindrance to the effective management of chronic diseases whenever an injectable therapy might be required, especially in case of frequent administrations. Psoriasis, a chronic dermatologic disease, can be effectively treated with biologic drugs administered subcutaneously. Thankfully, anti-IL-23 drugs require few administrations per year and are available in prefilled pens that hide the needle, thus representing a convenient option in patients with trypanophobia. METHODS: An observational multicentric study was conducted on patients with moderate-to-severe psoriasis who were treated with 75 mg × 2 risankizumab prefilled syringe therapy for more than 6 months and reported a loss of efficacy measured by the Psoriasis Area and Severity Index (PASI) from PASI 90 to PASI 75 attributed to a reduction of adherence due to trypanophobia. The patients were switched to 1 prefilled pen of risankizumab 150 mg and asked to fill out the Self-Injection Assessment Questionnaire (SIAQ) before and after the injection at week 0 and at the following administration after 12 weeks. Subjects scored each item of the SIAQ on a 5-point scale, scores were later transformed from 0 (worst experience) to 10 (best experience). RESULTS: Twenty-two patients were enrolled. The mean SIAQ predose domain scores were 5.5 for feelings about injection, 6.2 for self-confidence, and 6.4 for satisfaction with self-injection. After dose scores were higher (> 8.5) for each of the six domains at Week 0 and even higher after 12 weeks (> 9.0). CONCLUSIONS: User-friendly devices, such as prefilled pens, and a lower number of injections improved patient satisfaction in a group of patients with psoriasis on treatment with biologic drugs. We believe that treatment adherence could be positively influenced by such changes in the way of administration of a biologic treatment.
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Psoríase , Autoadministração , Humanos , Psoríase/tratamento farmacológico , Psoríase/psicologia , Autoadministração/instrumentação , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Injeções Subcutâneas , Anticorpos Monoclonais/administração & dosagem , Resultado do Tratamento , Satisfação do Paciente , Seringas , Idoso , Inquéritos e Questionários , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Recently, several case-control studies demonstrated an association between gliptins and bullous pemphigoid (BP) occurrence. However, data on the clinical and immunologic features of gliptin-associated bullous pemphigoid (GABP) are controversial. OBJECTIVE: This study aimed to clinically and immunologically characterize a large cohort of GABP patients to get an insight into the pathophysiology of this emerging drug-induced variant of BP. METHODS: Seventy-four GABP patients were prospectively enrolled and characterized from 9 different Italian dermatology units between 2013 and 2020. RESULTS: Our findings demonstrated the following in the GABP patients: (1) a noninflammatory phenotype, which is characterized by low amounts of circulating and skin-infiltrating eosinophils, is frequently found; (2) immunoglobulin (Ig)G, IgE, and IgA humoral responses to BP180 and BP230 antigens are reduced in frequency and titers compared with those in patients with idiopathic BP; (3) IgG reactivity targets multiple BP180 epitopes other than noncollagenous region 16A. LIMITATIONS: A limitation of the study is that the control group did not comprise only type 2 diabetes mellitus patients with BP. CONCLUSION: GABP patients show peculiar features of anti-BP180 and -BP230 humoral responses, laying the foundation for diagnostic improvements and getting novel insights into understanding the mechanism of BP onset.
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Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Penfigoide Bolhoso , Autoanticorpos , Autoantígenos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Humanos , Imunoglobulina G , Colágenos não FibrilaresRESUMO
Drug-induced bullous pemphigoid (DBP) associated to biologics administered for psoriasis is rare. DBP has been described especially in association with anti-TNF-α drugs and anti-IL12 and 23, but never in relation to guselkumab (anti-IL23). We report the case of a 76-year-old male patient with severe psoriasis (PASI 20), presenting with generalized tense bullae and erosions after being recently switched to guselkumab therapy. Histology and direct immunofluorescence confirmed the suspect of bullous pemphigoid (BP). Guselkumab administration was interrupted, low-dose oral corticosteroid therapy was introduced and after only 1-month remission was obtained with no new lesions appearing. As outlined in the presented case, DBP's onset typically follows the introduction of a new drug in patients taking polypharmacy. In addition, DBP may spontaneously regress after discontinuation of the triggering drug and it responds very rapidly to steroid therapy. Up to date, DBP has been described after biological therapy for psoriasis in 11 patients, following administration of ustekinumab, efalizumab, etanercept, secukinumab, and adalimumab. Conversely, DBP after guselkumab therapy for psoriasis has never been reported in published studies. We highlight the need to face and document increasing, though rare, side effects of biologic therapies, as new biologic molecules are being constantly developed and administered to psoriatic patients, to promptly interrupt treatment when needed.
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Penfigoide Bolhoso , Psoríase , Idoso , Anticorpos Monoclonais Humanizados , Humanos , Masculino , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/diagnóstico , Penfigoide Bolhoso/tratamento farmacológico , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Ustekinumab/uso terapêuticoRESUMO
Lupus erythematosus (LE) is an autoimmune disease with a wide range of clinical and cutaneous manifestations. Along with the well-known typical cutaneous manifestations of LE, some cutaneous manifestations are rarer, but still characteristic, enabling the dermatologist and the general practitioner who know them to suspect cutaneous LE (CLE) and investigate a possible underlying systemic involvement. Indeed, not infrequently a skin manifestation is the first presentation of systemic LE (SLE), and >75% of SLE patients show signs of skin disease during the course of the illness. Especially, SLE involvement occurs in cases of acute CLE, while it is uncommon in subacute CLE and rare in chronic CLE. This review aims to concentrate especially on atypical cutaneous manifestations of LE to enable the clinician to diagnose even the rarest forms of CLE.
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Doenças Autoimunes , Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapiaRESUMO
is missing (Quiz).
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Exantema , Prurido , Fazendeiros , Humanos , Prurido/diagnóstico , Prurido/etiologia , PeleRESUMO
BACKGROUND: Traditionally, KOH microscopy and fungal culture are the two preferred tests as gold standard for diagnosis of onychomycosis. Recently, other diagnostic methods have been developed to improve the microbiological diagnosis. The EUROArray dermatomycosis kit is a PCR-based microarray test system for the detection and direct identification of species that are most frequently involved in skin and nail infections. OBJECTIVES: Our primary aim was to evaluate the real-life applicability of the EUROArray dermatomycosis kit in the diagnosis of onychomycoses. In addition, we compared the aetiology of onychomycoses found in our patients with those described in the literature. PATIENTS/METHODS: We prospectively studied consecutive 100 patients with suspected onychomycoses. Samples of suspect toenails were taken as part of routine medical management. Nail specimens were evaluated by means of three diagnostic methods: KOH preparation, culture and EUROArray dermatomycosis kit. RESULTS: Onychomycosis was diagnosed in 47/100 patients who proved positive on at least one reference diagnostic test and in 49/100 patients who proved positive on PCR. The combination of microscopy and PCR had better sensitivity than microscopy (p = .0397), fungal culture (p = .0061) and PCR alone (p = .0117). Moulds were more frequently positive in culture than in PCR (p = .033). Dermatophytes proved positive more frequent than moulds and yeasts in both culture and PCR; in particular, Trichophyton interdigitale was the most frequent pathogen. CONCLUSIONS: In conclusion, introducing EUROArray dermatomycosis kit into the diagnostic algorithm of onychomycosis increases the sensitivity of direct microscopy and yields more rapid results than culture.
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Onicomicose , Humanos , Microscopia , Unhas/microbiologia , Onicomicose/diagnóstico , Onicomicose/microbiologia , Reação em Cadeia da Polimerase , Coloração e RotulagemRESUMO
Hintergrund: Unbehandelt kann das Basalzellkarzinom (BCC) erhebliche Gewebezerstörungen verursachen. Die komplette chirurgische Exzision ist die Behandlung der Wahl. Allerdings stellt es besonders im Gesichts- und Halsbereich eine Herausforderung dar, den Tumor vollständig zu entfernen und möglichst viel gesundes Gewebe zu erhalten. Material und Methoden: Bereits exzidierte kleine BCC (≤ 1 cm) von Kopf oder Hals wurden retrospektiv analysiert. Verglichen wurde die histologisch kontrolliert angemessene Breite des Resektionsrandes nach präoperativer dermatoskopischer Untersuchung (Fälle) im Vergleich zur rein klinischen Untersuchung (Kontrollen), sowie die Rezidivrate. Ergebnisse: Bei 281 BCC: 6 % (8/139) der Fälle und 8 % (12/142) der Kontrollen zeigten inadäquate basale Resektionsränder; 4 % (5/139) der Fälle und 20 % (29/142) der Kontrollen zeigten inadäquate laterale Resektionsränder (P < 0.001). Laterale Resektionsränder von 3 mm waren in 0 % (15/66) der Fälle, jedoch in 15 % (10/66) der Kontrollen inadäquat (P >0.005); laterale Resektionsränder von 1-2 mm waren in 7 % (5/73) der Fälle und in 25 % (19/76) der Kontrollen inadäquat (P < 0.01). Rezidive traten in den Fällen mit 3 mm Resektionsrand in 1,5 % auf, in den Fällen mit 1-2 mm Resektionsrand bei 0 %, und bei den Kontrollen bei 7,7 %. Schlussfolgerung: Für BCC im Kopf- und Halsbereich erscheint ein Resektionsrand von 3 mm angemessen, sofern das BCC klein, dermatoskopisch gut definiert und wenig aggressiv ist. Hier zeigten sich operative Heilungsraten von 100 % mit 1,5 % Rezidiven. Resektionsränder von 1-2 mm sollten nur für BCC in sehr schwierig zu behandelnden Bereichen in Betracht gezogen werden, da die Heilungsrate hier nur bei 93 % lag.
RESUMO
BACKGROUND: Basal cell carcinoma (BCC) can cause extensive tissue damage if untreated. Complete surgical excision is the treatment of choice, but especially in the head-and neck area, defining both radical and healthy skin sparing surgical margins is complex. MATERIALS AND METHODS: Excised, small (≤ 1 cm), BCCs of the head and neck were retrospectively analyzed, comparing histological properness of surgical margins after clinical-dermatoscopical preoperative evaluation (cases), vs. clinical evaluation only (controls) and recurrences. RESULTS: Of 281 BCCs: 6 % (8/139) of cases and 8 % (12/142) of controls had unproper deep margins; 4 % (5/139) of cases, 20 % (29/142) of controls had unproper lateral margins (P < 0.001). Surgical 3 mm lateral margins were unproper in 0 % (15/66) of cases, 15 % (10/66) of controls (P > 0.005); surgical 1-2 mm lateral margins were unproper in 7 % (5/73) of cases, 25 % (19/76) of controls (P < 0.01). Of cases excised at 3 mm, 1-2 mm, and controls, 1.5 %, 0 %, and 7.7 % recurred, respectively. CONCLUSIONS: BCC excision at 3 mm may be appropriate in the head and neck for small, dermatoscopically well-defined and non-aggressive BCCs, attaining surgical cure rates of 100 % and 1.5 % recurrences. Excision at 1-2 mm should be reserved only for BCCs in very difficult-to-treat areas, as the surgical cure rate was only 93 %.
Assuntos
Carcinoma Basocelular , Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Carcinoma Basocelular/patologia , Carcinoma Basocelular/cirurgia , Estudos de Casos e Controles , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Margens de Excisão , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgiaRESUMO
Although dermatomyositis is known to be a possible paraneoplastic syndrome, often in the setting of gynecological cancers, Wong-type dermatomyositis-a rare variant of dermatomyositis-has not been clearly associated with internal malignancies to date. There is only one report from Japan of a woman who developed Wong-type dermatomyositis together with the recurrence of uterine cancer. We report the case of a Caucasian patient who presented with infrequent Wong-type dermatomyositis with positive anti-TIF1γ antibodies; screening for internal malignancies revealed fallopian tube carcinoma.
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Dermatomiosite , Neoplasias dos Genitais Femininos , Síndromes Paraneoplásicas , Autoanticorpos , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Feminino , Neoplasias dos Genitais Femininos/complicações , Humanos , Japão , Síndromes Paraneoplásicas/complicações , Síndromes Paraneoplásicas/diagnósticoRESUMO
During the COVID-19 pandemic, various cutaneous manifestations have been described as associated with SARS-CoV2 infection. It is debated if skin lesions could represent a diagnostic or prognostic indicator. Specifically, it is unclear whether skin lesions may be used to perform an early diagnosis and/or to predict worse outcomes. In this review, we described the cutaneous signs so far reported as COVID-19-related and discussed their incidence, clinico-pathological features, and diagnostic and prognostic value.
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COVID-19 , Dermatopatias , COVID-19/complicações , Humanos , Pandemias , RNA Viral , SARS-CoV-2 , Dermatopatias/diagnóstico , Dermatopatias/epidemiologia , Dermatopatias/etiologiaRESUMO
Lack of safety data on pregnant women determines difficulty in choosing the correct biologic agent to treat psoriasis in women of childbearing potential. Studies have postulated a role of IL-23 in unexplained recurrent spontaneous abortions. This gives rise to consideration about use of anti-IL-23 drugs in treatment of psoriasis in women of childbearing potential.
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Artrite Psoriásica , Psoríase , Feminino , Humanos , Interleucina-23 , Gravidez , Psoríase/diagnóstico , Psoríase/tratamento farmacológicoRESUMO
Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous skin disorder, characterized by erythematous plaques with elevated borders and hypopigmented center, occurring mainly on sun exposed-skin. Histologically it presents with elastophagocytosis and elastolysis. There is no established first line treatment for AEGCG, especially for the generalized form. In a small number of cases, antimalarial drugs and tranilast, associated to topical or oral steroids, have been proposed to treat generalized AEGCG with partial benefits. We herein present the case of a patient with AEGCG aged 74 years, who was unresponsive to classical therapies, and then successfully treated with methotrexate.
Assuntos
Granuloma Anular , Granuloma de Células Gigantes , Dermatopatias , Idoso , Granuloma Anular/diagnóstico , Granuloma Anular/tratamento farmacológico , Granuloma de Células Gigantes/diagnóstico , Granuloma de Células Gigantes/tratamento farmacológico , Humanos , Metotrexato/uso terapêutico , PeleRESUMO
BACKGROUND: Ultraviolet (UV) radiation has numerous beneficial effects on human health, including stimulating vitamin D and serotonin production and immuno-regulatory activities. Conversely, UV radiation is also classified as a group one carcinogen by the International Agency for Research on Cancer. PURPOSE: To investigated the effects of UV radiation avoidance in melanoma patients in terms of vitamin D levels but also of bone mineral density and trabecular bone microarchitecture. METHODS: We conducted an observational study investigating the effects of UV radiation avoidance in 31 melanoma patients in terms of vitamin D levels but also of bone mineral density and trabecular bone microarchitecture by using dual-energy X-ray absorptiometry scan. Data were compared with two control groups of healthy subjects, who were chronically exposed or not exposed to UV radiation during their lifetime. RESULTS: Melanoma patients had on average slightly lower levels of vitamin D, without reaching statistical significance (P = .135). No significant difference was found across the three groups on T-scores of femoral neck (P = .544), of total hip (P = .617) and of lumbar spine P = .155). No significant difference was found on and trabecular bone score across exposure groups (P = .895). CONCLUSION: UV radiation avoidance does not seem to significantly impact vitamin D levels nor bone health in melanoma patients. Thus, UV protective behavior is advisable for all melanoma patients.
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Osso e Ossos , Melanoma , Raios Ultravioleta , Absorciometria de Fóton , Densidade Óssea , Humanos , Raios Ultravioleta/efeitos adversos , Vitamina DRESUMO
BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.
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Micose Fungoide , Neoplasias Cutâneas , Consenso , Técnica Delphi , Humanos , Micose Fungoide/tratamento farmacológico , Terapia PUVA , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
BACKGROUND: Peristomal pyoderma gangrenosum (PPG) is a variant of pyoderma gangrenosum (PG). It results from a pathergy response to trauma from effluent from the ostomy or secondary to trauma caused by removal of the ostomy appliance adhesive in contact with the skin. Currently, no evidence-based guidelines for the management of PPG exist. This case study reports a dramatic response to crushed corticosteroid tablets in a patient who proved refractory to first- and second-line treatments of her PPG and several surgeries. CASE: Ms T. was a 39-year-old woman with Crohn's disease who underwent several ileostomies, developed PPG, and failed treatment with adalimumab. Her PPG was successfully treated topically with crushed prednisone tablets. CONCLUSION: We found that crushed corticosteroid tablets were an effective treatment of PPG, due to the ability to reduce pain and allow adhesion of the ostomy appliance.
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Estomia , Pioderma Gangrenoso , Corticosteroides , Adulto , Feminino , Humanos , Ileostomia/efeitos adversos , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/etiologia , ComprimidosRESUMO
OBJECTIVES: Fibroblast-to-myofibroblast transition and extracellular matrix overproduction represent progressive events in chronic inflammatory and fibrotic diseases, in which TGFß1 is one of the key mediators. Phosphodiesterase 4 (PDE4) acts as a proinflammatory enzyme through the degradation of cyclic adenosine monophosphate and it is overexpressed in skin fibroblasts. The study investigated how apremilast (a PDE4 inhibitor) interferes with the intracellular signalling pathways responsible for the TGFß1-induced fibroblast-to-myofibroblast transition and profibrotic extracellular matrix protein synthesis. METHODS: Cultured human skin fibroblasts were stimulated with TGFß1 (10 ng/ml) alone or combined with apremilast (1 and 10 µM) for 4, 16 and 24 h. Other aliquots of the same cells were previously stimulated with TGFß1 and then treated with apremilast (1 and 10 µM) for 4, 16 and 24 h, always under stimulation with TGFß1. Gene and protein expression of αSMA, type I collagen (COL1) and fibronectin were evaluated, together with the activation of small mothers against decapentaplegic 2 and 3 (Smad2/3) and extracellular signal-regulated kinase (Erk1/2) proteins. RESULTS: Apremilast reduced the TGFß1-induced increase in αSMA, COL1 and fibronectin gene expression at 4 and 16 h, and protein synthesis at 24 h of treatment in cultured fibroblasts, even for cells already differentiated into myofibroblasts by way of a previous stimulation with TGFß1. Apremilast inhibited the TGFß1-induced Smad2/3 and Erk1/2 phosphorylation at 15 and 30 min. CONCLUSION: Apremilast seems to inhibit in vitro the fibroblast-to-myofibroblast transition and the profibrotic activity induced by TGFß1 in cultured human skin fibroblasts by downregulating Smad2/3 and Erk1/2 intracellular signalling pathways.
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Anti-Inflamatórios não Esteroides/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Pele/efeitos dos fármacos , Talidomida/análogos & derivados , Fator de Crescimento Transformador beta1/farmacologia , Actinas/metabolismo , Células Cultivadas , Colágeno Tipo I/metabolismo , Feminino , Fibroblastos/fisiologia , Fibronectinas/metabolismo , Humanos , Pessoa de Meia-Idade , Miofibroblastos/fisiologia , Pele/citologia , Talidomida/farmacologia , Fator de Crescimento Transformador beta1/antagonistas & inibidoresRESUMO
Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and internal organs. Its pathogenesis, which is still poorly understood, features three main pathogenic moments: an initial diffuse vasculopathy followed by low-grade inflammation and a subsequent tissue fibrosis. Numerous evidences support the role of a Th2-oriented immune response during both the inflammatory and the fibrotic phase of SSc. Levels of IL-4, IL-13 and CXCL4 are higher in the serum of SSc patients compared to healthy controls. Fibrotic tissue in SSc displays a Th2 polarized CD4+ cell infiltration, influencing fibroblast phenotype and inducing collagen and extra cellular matrix protein synthesis. In tight skin mice the administration of neutralizing anti-IL-4 antibodies prevents the development of dermal fibrosis. Back-crossing these mice onto a genetic background that cannot respond to IL-4 prevents skin sclerosis. In SSc, CD8+ T lymphocytes secrete IL-13 and mediate dermal fibrosis and have skin-homing receptors. Incubation with healthy dermal fibroblasts results in elevation of extracellular matrix, which can be reduced with anti-IL13 antibodies. Specifically, IL-4 and IL-13 take part in the inflammatory phase, contribute to the transition from the inflammatory to the fibrotic phase and maintain a profibrotic state in affected organs, mediating the interaction between T cells and fibroblasts. Blocking the cross-talk between these cell types by acting on the soluble cytokines, on their receptors on cell surfaces or on intracellular signaling pathways could constitute a new therapeutic approach.
Assuntos
Interleucina-13/sangue , Interleucina-4/sangue , Escleroderma Sistêmico/metabolismo , Transdução de Sinais/imunologia , Células Th2/imunologia , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Azetidinas/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibrose/imunologia , Fibrose/metabolismo , Fibrose/patologia , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Janus Quinases/antagonistas & inibidores , Camundongos , Purinas/farmacologia , Pirazóis/farmacologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Transdução de Sinais/genética , Sulfonamidas/farmacologiaRESUMO
BACKGROUND: Biologic therapy for psoriasis is effective but not always long-lasting and sometimes needs to be switched. OBJECTIVE: We aimed to evaluate the drug survival (ie, the time from initiation to discontinuation) of each biologic and the factors affecting survival to identify better switching strategies and improve drug survival. METHODS: In total, 195 psoriasis patients treated in our unit during 2006-2018 were retrospectively observed. Descriptive statistical analyses and logistic regression models were performed. Kaplan-Meier survival curves and multivariate Cox models adjusted for confounding variables were used to estimate and compare drug survival. RESULTS: Overall, 90.6% of patients achieved an ≥75% reduction in their baseline Psoriasis Area and Severity Index score. In 2018, the most frequently used biologic was ustekinumab (47/169, 27.8%). Patients with higher baseline Psoriasis Area and Severity Index scores were more likely to be switched (P = .0399, odds ratio 1.08). In naive patients, ustekinumab showed longer drug survival (>7.0 years), but in biologic-experienced patients, we found no significant differences in drug survival. Previous biologic therapies increased the need for switching (P = .014, hazard ratio 1.20). Switching between biologic classes yielded longer drug survival than switching within biologic classes (P = .003, hazard ratio 0.48). LIMITATIONS: As a single-center, retrospective real-life study, the data were not perfectly homogeneous. CONCLUSION: Switching between biologic classes might increase drug survival but retrospective studies designed ad hoc are needed to confirm this better switching strategy.
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Produtos Biológicos/administração & dosagem , Terapia Biológica/métodos , Substituição de Medicamentos/estatística & dados numéricos , Psoríase/tratamento farmacológico , Centros Médicos Acadêmicos , Adalimumab/administração & dosagem , Adulto , Idoso , Esquema de Medicação , Etanercepte/administração & dosagem , Feminino , Humanos , Itália , Estimativa de Kaplan-Meier , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Psoríase/diagnóstico , Psoríase/epidemiologia , Medição de Risco , Índice de Gravidade de Doença , Ustekinumab/administração & dosagemRESUMO
Bullous pemphigoid, mucous membrane pemphigoid, and pemphigus vulgaris are different cutaneous autoimmune blistering diseases, with complex pathogenic mechanisms. In all of them, a type-2 response is thought to have a central role. Interleukin 4 and Interleukin 13 are crucial cytokines in type-2 response. Treatment of these conditions is often challenging. Dupilumab, a recombinant fully human IgG4 monoclonal antibody with binding specificity to human interleukin-4 receptor IL-4Rα, has the potential to inhibit both IL-4 and IL-13. We propose IL-4Rα as a theoretical drug target for cutaneous autoimmune bullous diseases.