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BACKGROUND: Biologics are among the most effective therapies for psoriasis. However, many patients are only introduced to them at advanced stages of the disease course. OBJECTIVES: Our aim was to identify predictors of initiating biologic therapy in patients with psoriasis and compare patients initiating biologics early versus late in their disease course. METHODS: Kaplan-Meier curves visualized time to biologic initiation, while Cox regression models further explored variables as predictors of biologic initiation. Mann-Whitney U and chi-squared tests compared patients who started biologics early with those who began biologics later in the disease course. RESULTS: Our primary analysis included 233 psoriasis patients. Cox regression showed that age at diagnosis (P = 0.007), general physical well-being (P = 0.02), and nail psoriasis severity (P = 0.02) were significantly associated with time to biologic initiation. Our secondary analysis, the comparisons between patients starting biologics early versus later in the disease course, included a total of 378 patients. The median (interquartile range [IQR]) age at diagnosis was 34.5 (25.0-51.2) years for patients initiating biologics within 5 years, compared to 22.0 (15.0-32.8) years for patients initiating biologics later (P < 0.0001). The median (IQR) age at initiation was 37.0 (27.0-53.2) and 45.0 (36.0-55.0) years for patients initiating biologics earlier versus later than 5 years (P = 0.04). CONCLUSIONS: Age at diagnosis, general well-being, and severity of nail psoriasis significantly predicted future initiation of biologic treatment. Patients initiating biologics early in their disease course were generally older at diagnosis but younger at the time of biologic initiation compared to patients initiating biologics later in their disease course.
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AI image classification algorithms have shown promising results when applied to skin cancer detection. Most public skin cancer image datasets are comprised of dermoscopic photos and are limited by selection bias, lack of standardization, and lend themselves to development of algorithms that can only be used by skilled clinicians. The SLICE-3D ("Skin Lesion Image Crops Extracted from 3D TBP") dataset described here addresses those concerns and contains images of over 400,000 distinct skin lesions from seven dermatologic centers from around the world. De-identified images were systematically extracted from sensitive 3D Total Body Photographs and are comparable in optical resolution to smartphone images. Algorithms trained on lower quality images could improve clinical workflows and detect skin cancers earlier if deployed in primary care or non-clinical settings, where photos are captured by non-expert physicians or patients. Such a tool could prompt individuals to visit a specialized dermatologist. This dataset circumvents many inherent limitations of prior datasets and may be used to build upon previous applications of skin imaging for cancer detection.
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Neoplasias Cutâneas , Neoplasias Cutâneas/diagnóstico por imagem , Humanos , Algoritmos , Imageamento Tridimensional , Pele/diagnóstico por imagemRESUMO
With rising melanoma incidence and mortality, early detection and surgical removal of primary lesions is essential. Multispectral imaging is a new, non-invasive technique that can facilitate skin cancer detection by measuring the reflectance spectra of biological tissues. Currently, incident illumination allows little light to be reflected from deeper skin layers due to high surface reflectance. A pilot study was conducted at the University Hospital Basel to evaluate, whether multispectral imaging with direct light coupling could extract more information from deeper skin layers for more accurate dignity classification of melanocytic lesions. 27 suspicious pigmented lesions from 23 patients were included (6 melanomas, 6 dysplastic nevi, 12 melanocytic nevi, 3 other). Lesions were imaged before excision using a prototype snapshot mosaic multispectral camera with incident and direct illumination with subsequent dignity classification by a pre-trained multispectral image analysis model. Using incident light, a sensitivity of 83.3% and a specificity of 58.8% were achieved compared to dignity as determined by histopathological examination. Direct light coupling resulted in a superior sensitivity of 100% and specificity of 82.4%. Convolutional neural network classification of corresponding red, green, and blue lesion images resulted in 16.7% lower sensitivity (83.3%, 5/6 malignant lesions detected) and 20.9% lower specificity (61.5%) compared to direct light coupling with multispectral image classification. Our results show that incorporating direct light multispectral imaging into the melanoma detection process could potentially increase the accuracy of dignity classification. This newly evaluated illumination method could improve multispectral applications in skin cancer detection. Further larger studies are needed to validate the camera prototype.
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Melanoma , Nevo Pigmentado , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico por imagem , Melanoma/classificação , Melanoma/patologia , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/diagnóstico , Feminino , Nevo Pigmentado/diagnóstico por imagem , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/classificação , Nevo Pigmentado/patologia , Masculino , Pessoa de Meia-Idade , Adulto , Projetos Piloto , Idoso , Melanócitos/patologia , Iluminação/métodos , Processamento de Imagem Assistida por Computador/métodos , Sensibilidade e EspecificidadeRESUMO
Since December 2019, the COVID-19 pandemic has profoundly affected healthcare. The real effects of the COVID-19 pandemic on skin cancer are still unclear, more than 3 years later. This study aims to summarise the pandemic's impact on skin cancer diagnosis and outcome. A systematic review and meta-analysis was conducted, selecting studies comparing skin cancer diagnosis and prognosis post-pandemic with pre-pandemic data. A total of 27 papers were reviewed including 102,263 melanomas and 271,483 keratinocyte carcinomas. During the initial pandemic months (January-July 2020), melanoma surgeries dropped by 29.7% and keratinocyte carcinomas surgeries by 50.8%. Early pandemic tumours exhibited greater thickness and stage. In a long-term period beyond the initial months, melanoma surgeries decreased by 9.3%, keratinocyte carcinomas by 16.6%. No significant differences were observed in the Breslow thickness of melanomas after the start of the pandemic (mean difference 0.06, 95% confidence interval -0.46, 0.58). Melanomas operated on post-pandemic onset had an increased risk of ulceration (odds ratio 1.35, 95% confidence interval 1.22-1.50). Keratinocyte carcinomas showed increased thickness and worsened stage post-pandemic. However, studies included were mostly retrospective and cross-sectional, reporting diverse data. This review indicates that the pandemic likely caused delays in skin cancer diagnosis and treatment, potentially impacting patient outcomes.
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COVID-19 , Queratinócitos , Melanoma , Neoplasias Cutâneas , Humanos , COVID-19/epidemiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgia , Melanoma/epidemiologia , Melanoma/cirurgia , Melanoma/diagnóstico , Queratinócitos/patologia , SARS-CoV-2 , Prognóstico , Estadiamento de NeoplasiasRESUMO
The genesis of subacute cutaneous lupus erythematosus (SCLE) is multifactorial and includes idiopathic, drug-related and paraneoplastic etiologies. This article reports the case of a 70-year-old female patient with paraneoplastic SCLE in whom a lung adenocarcinoma was detected during the extended examination. A paraneoplastic SCLE should be considered when a patient with SCLE presents with lesions in regions of the skin not exposed to sunlight and beginning B symptoms.
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Neoplasias Pulmonares , Lúpus Eritematoso Cutâneo , Síndromes Paraneoplásicas , Humanos , Feminino , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Cutâneo/diagnóstico , Idoso , Síndromes Paraneoplásicas/patologia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/radioterapia , Diagnóstico DiferencialRESUMO
BACKGROUND: Artificial intelligence (AI) shows promising potential to enhance human decision-making as synergistic augmented intelligence (AuI), but requires critical evaluation for skin cancer screening in a real-world setting. OBJECTIVES: To investigate the perspectives of patients and dermatologists after skin cancer screening by human, artificial and augmented intelligence. METHODS: A prospective comparative cohort study conducted at the University Hospital Basel included 205 patients (at high-risk of developing melanoma, with resected or advanced disease) and 8 dermatologists. Patients underwent skin cancer screening by a dermatologist with subsequent 2D and 3D total-body photography (TBP). Any suspicious and all melanocytic skin lesions ≥3 mm were imaged with digital dermoscopes and classified by corresponding convolutional neural networks (CNNs). Excisions were performed based on dermatologist's melanoma suspicion, study-defined elevated CNN risk-scores and/or melanoma suspicion by AuI. Subsequently, all patients and dermatologists were surveyed about their experience using questionnaires, including quantification of patient's safety sense following different examinations (subjective safety score (SSS): 0-10). RESULTS: Most patients believed AI could improve diagnostic performance (95.5%, n = 192/201). In total, 83.4% preferred AuI-based skin cancer screening compared to examination by AI or dermatologist alone (3D-TBP: 61.3%; 2D-TBP: 22.1%, n = 199). Regarding SSS, AuI induced a significantly higher feeling of safety than AI (mean-SSS (mSSS): 9.5 vs. 7.7, p < 0.0001) or dermatologist screening alone (mSSS: 9.5 vs. 9.1, p = 0.001). Most dermatologists expressed high trust in AI examination results (3D-TBP: 90.2%; 2D-TBP: 96.1%, n = 205). In 68.3% of the examinations, dermatologists felt that diagnostic accuracy improved through additional AI-assessment (n = 140/205). Especially beginners (<2 years' dermoscopic experience; 61.8%, n = 94/152) felt AI facilitated their clinical work compared to experts (>5 years' dermoscopic experience; 20.9%, n = 9/43). Contrarily, in divergent risk assessments, only 1.5% of dermatologists trusted a benign CNN-classification more than personal malignancy suspicion (n = 3/205). CONCLUSIONS: While patients already prefer AuI with 3D-TBP for melanoma recognition, dermatologists continue to rely largely on their own decision-making despite high confidence in AI-results. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04605822).
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INTRODUCTION: Erythema nodosum (EN) is the most common form of panniculitis that predominantly affects the shins. While EN in atypical sites has been described by many authors, there are currently only case studies published on this topic. This study aimed to evaluate clinical differences between patients suffering from EN on the shins, compared to patients with EN in atypical locations. METHODS: We analyzed 105 patients in a retrospective, single-center study at a university hospital in Switzerland. Typical EN was defined as lesions, found only on the lower legs, while atypical EN as lesions on the upper legs, trunk, arms, or face, only or in addition to lesions on the lower legs. The patients were assessed for age, gender, dermatologic history, time until first medical consultation, time to diagnosis, and time until remission. Further, etiology, symptoms, and applied therapies were investigated. Findings were then compared between the typical and atypical EN cohorts. RESULTS: Overall, we included 70 patients (37.99 ± 15.67 [3-81] years) with EN solely on the shins and 35 patients (41.27 ± 16.85 [9-76] years) with EN on other locations. Interestingly, time until diagnosis was significantly shorter in atypical EN (p = 0.034, 1.14 ± 4.68 vs. 0.46 ± 1.14 months). Time to remission was similar in both groups (3.61 ± 2.73 vs. 3.05 ± 2.86 months, respectively). Sarcoidosis was the only etiologic factor significantly more frequent in atypical EN compared to typical EN (23% vs. 9%, p = 0.042). Besides that, solely subtle differences were seen regarding etiology, gender, age at onset, course of the disease, and symptoms. CONCLUSIONS: Our study suggests that only minor alterations between both study populations exist. Significant differences were found in time to diagnosis (shorter for atypical EN), as well as in sarcoidosis as an etiologic factor (more frequent in atypical EN). While adalimumab was only prescribed in atypical EN cases, prognosis seems to be similar for typical and atypical EN (similar time to remission, similar amount of reoccurring cases). Due to the limited sample size, however, our study population may have been too small to detect the relevant differences, and bigger studies may be needed.
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Eritema Nodoso , Paniculite , Sarcoidose , Humanos , Eritema Nodoso/diagnóstico , Estudos Retrospectivos , Paniculite/complicações , Paniculite/diagnóstico , Paniculite/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. OBJECTIVES: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). METHODS: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. RESULTS: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87-9.68) compared to CSTs (7.08, CI 5.39-9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. CONCLUSION: Females were associated with a significantly higher rate of ADRs and drug-related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient-tailored management of psoriasis.
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Produtos Biológicos , Psoríase , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Suíça/epidemiologia , Caracteres Sexuais , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Fatores Biológicos , Produtos Biológicos/efeitos adversos , Sistema de Registros , Resultado do TratamentoRESUMO
The incidence of cutaneous melanoma continues to rise despite the increased use of sunscreens within the last several decades. Some research even suggests that the use of sunscreen is associated with increased rates of melanoma. Given the aggressive, and often deadly, nature of cutaneous melanoma, the aim of this communication is to better elucidate the relationship between sunscreen use and melanoma development and if there are other preventative measures to be aware of. A search was performed to identify the studies that have investigated melanoma development in individuals who used sunscreen and those who did not. Study limitations and possible confounding variables were identified, which guided a subsequent search to determine what data were available to support that these limitations and confounding variables may explain the perplexing association between sunscreen use and melanoma development. Five hypotheses were generated, which were related to increased awareness and reporting, the relationship between sunscreen use and the duration of sun exposure, the importance of broad-spectrum protection, and the effect of sunscreen on reactive oxygen species formation. The main conclusion is that more recent studies that control for confounding variables are required to determine the true effect of adequate broad-spectrum sunscreen use today on the development of melanoma.
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BACKGROUND: Teledermatology is currently finding its place in modern health care worldwide as a rapidly evolving field. OBJECTIVE: The aim of this study was to investigate the acceptance of teledermatology compared to in-person consultation from the perspective of patients and professionals. METHODS: This multicenter, cross-sectional pilot study was performed at secondary and tertiary referral centers of dermatology in Switzerland from August 2019 to January 2020. A customized questionnaire addressing demographics and educational data, experience with telemedicine, and presumed willingness to replace in-patient consultations with teledermatology was completed by dermatological patients, dermatologists, and health care workers in dermatology. RESULTS: Among a total of 664 participants, the ones with previous telemedicine experience (171/664, 25.8%) indicated a high level of overall experience with it (patients: 73/106, 68.9%, dermatologists: 6/8, 75.0%, and health care workers: 27/34, 79.4%). Patients, dermatologists, and health care workers were most likely willing to replace in-person consultations with teledermatology for minor health issues (353/512, 68.9%; 37/45, 82.2%; and 89/107, 83.2%, respectively). We observed a higher preference for telemedicine among individuals who have already used telemedicine (patients: P<.001, dermatologists: P=.03, and health care workers, P=.005), as well as among patients with higher educational levels (P=.003). CONCLUSIONS: This study indicates that the preference for teledermatology has a high potential to increase over time since previous experience with telemedicine and a higher level of education were associated with a higher willingness to replace in-patient consultations with telemedicine. We assume that minor skin problems are the most promising issue in teledermatology. Our findings emphasize the need for dermatologists to be actively involved in the transition to teledermatology. TRIAL REGISTRATION: ClinicalTrials.gov NCT04495036; https://classic.clinicaltrials.gov/ct2/show/NCT04495036.
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BACKGROUND: Convolutional neural networks (CNNs) have outperformed dermatologists in classifying pigmented skin lesions under artificial conditions. We investigated, for the first time, the performance of three-dimensional (3D) and two-dimensional (2D) CNNs and dermatologists in the early detection of melanoma in a real-world setting. METHODS: In this prospective study, 1690 melanocytic lesions in 143 patients with high-risk criteria for melanoma were evaluated by dermatologists, 2D-FotoFinder-ATBM and 3D-Vectra WB360 total body photography (TBP). Excision was based on the dermatologists' dichotomous decision, an elevated CNN risk score (study-specific malignancy cut-off: FotoFinder >0.5, Vectra >5.0) and/or the second dermatologist's assessment with CNN support. The diagnostic accuracy of the 2D and 3D CNN classification was compared with that of the dermatologists and the augmented intelligence based on histopathology and dermatologists' assessment. Secondary end-points included reproducibility of risk scores and naevus counts per patient by medical staff (gold standard) compared to automated 3D and 2D TBP CNN counts. RESULTS: The sensitivity, specificity, and receiver operating characteristics area under the curve (ROC-AUC) for risk-score-assessments compared to histopathology of 3D-CNN with 95% confidence intervals (CI) were 90.0%, 64.6% and 0.92 (CI 0.85-1.00), respectively. While dermatologists and augmented intelligence achieved the same sensitivity (90%) and comparable classification ROC-AUC (0.91 [CI 0.80-1.00], 0.88 [CI 0.77-1.00]) with 3D-CNN, their specificity was superior (92.3% and 86.2%, respectively). The 2D-CNN (sensitivity: 70%, specificity: 40%, ROC-AUC: 0.68 [CI 0.46-0.90]) was outperformed by 3D CNN and dermatologists. The 3D-CNN showed a higher correlation coefficient for repeated measurements of 246 lesions (R = 0.89) than the 2D-CNN (R = 0.79). The mean naevus count per patient varied significantly (gold standard: 210 lesions; 3D-CNN: 469; 2D-CNN: 1324; p < 0.0001). CONCLUSIONS: Our study emphasises the importance of validating the classification of CNNs in real life. The novel 3D-CNN device outperformed the 2D-CNN and achieved comparable sensitivity with dermatologists. The low specificity of CNNs and the lack of automated counting of TBP nevi currently limit the use of augmented intelligence in clinical practice.
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Melanoma , Nevo Pigmentado , Nevo , Neoplasias Cutâneas , Humanos , Reprodutibilidade dos Testes , Estudos Prospectivos , Dermatologistas , Detecção Precoce de Câncer , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Melanoma/diagnóstico por imagem , Melanoma/patologia , Redes Neurais de Computação , Nevo/patologia , Nevo Pigmentado/diagnóstico por imagem , Fatores de Risco , FotografaçãoRESUMO
Introduction: The worldwide incidence of melanoma has been increasing rapidly in recent decades with Switzerland having one of the highest rates in Europe. Ultraviolet (UV) radiation is one of the main risk factors for skin cancer. Our objective was to investigate UV protective behavior and melanoma awareness in a high-risk cohort for melanoma. Methods: In this prospective monocentric study, we assessed general melanoma awareness and UV protection habits in at-risk patients (≥100 nevi, ≥5 dysplastic nevi, known CDKN2A mutation, and/or positive family history) and melanoma patients using questionnaires. Results: Between 01/2021 and 03/ 2022, a total of 269 patients (53.5% at-risk patients, 46.5% melanoma patients) were included. We observed a significant trend toward using a higher sun protection factor (SPF) in melanoma patients compared with at-risk patients (SPF 50+: 48% [n=60] vs. 26% [n=37]; p=0.0016). Those with a college or university degree used a high SPF significantly more often than patients with lower education levels (p=0.0007). However, higher educational levels correlated with increased annual sun exposure (p=0.041). Neither a positive family history for melanoma, nor gender or Fitzpatrick skin type influenced sun protection behavior. An age of ≥ 50 years presented as a significant risk factor for melanoma development with an odd's ratio of 2.32. Study participation resulted in improved sun protection behavior with 51% reporting more frequent sunscreen use after study inclusion. Discussion: UV protection remains a critical factor in melanoma prevention. We suggest that melanoma awareness should continue to be raised through public skin cancer prevention campaigns with a particular focus on individuals with low levels of education.
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Introduction: Immunotherapies have improved the prognosis of many cancer patients including patients with advanced melanoma. Immune checkpoint receptors including CTLA-4 and PD-1 have been established as main therapeutic targets for immunotherapy of melanoma. Although monotherapy is effective in melanoma patients, a dual therapy approach has been shown to be most effective. Dual checkpoint blockade, however, increases substantially the risk for immune-related adverse events (irAEs). Methods: In this study, we characterized peripheral immune cell subsets in patients with anti-PD-1 monotherapy and with dual immune receptors blockade targeting PD-1 and CTLA-4. Results: We found differences in peripheral T cells between patients who developed severe immune-related side effects and patients with mild irAEs. We identified several mainly changes in CD8+ T cell subsets in patients with severe irAE under dual PD-1 and CTLA-4 blockade. Discussion: This work suggests that peripheral immune cell dynamics could be associated with severe immune-related side effects in patients receiving immune checkpoint inhibitors. These changes could be used as future biomarkers in early diagnosis of irAEs.
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Antígeno CTLA-4 , Inibidores de Checkpoint Imunológico , Melanoma , Receptor de Morte Celular Programada 1 , Subpopulações de Linfócitos T , Feminino , Humanos , Masculino , Antígeno CTLA-4/antagonistas & inibidores , Quimioterapia Combinada , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Melanoma/imunologia , Melanoma/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , BiomarcadoresRESUMO
Cutaneous lichenoid drug eruptions (LDE) are adverse drug reactions (ADR) characterized by symmetric, erythematous, violaceous papules reminiscent but rarely fully characteristic of lichen planus (LP). We aimed to analyse the literature describing cases of LDE within the last 20 years to provide additional insight into culprit drugs, typical latency to onset of the eruption, the spectrum of clinical presentations, severity and management. A literature search was conducted in MEDLINE between January 2000 and 27 January 2021. The keywords 'lichenoid drug rash' and 'lichenoid drug eruption' were used. Cases were included if LDE diagnosis was made, and culprit drugs were identified. A total of 323 cases with LDE were identified from 163 published case reports and studies. The mean patient age was 58.5 years (1 month to 92 years), and 135 patients (41.8%) were female. Checkpoint inhibitors (CKI) were the most frequently reported culprit drugs (136 cases; 42.1%), followed by tyrosine kinase inhibitors (TKI) (39 cases; 12.0%) and anti-TNF-α-monoclonal antibodies (13 cases; 4.0%). The latency between initiation of the drug and manifestation was 15.7 weeks (range: 0.1-208 weeks). After discontinuing the culprit drug, the median time to resolution was 14.2 weeks (range: 0.71-416 weeks). One hundred thirty-six patients (42.1%) were treated with topical, and 54 patients (16.7%) with systemic glucocorticoids. Overall, we conclude that, albeit rare, LDE is challenging to diagnose ADR induced by mostly CKI, TKI, and biologics. Treatment modalities resemble that of lichen planus, and the culprit drugs had to be discontinued in only 26%, which is low compared with other types of adverse drug reactions. This is probably due to the low risk of aggravation (e.g. toxic epidermal necrolysis) if the drug is continued and the benefit/risk ratio favouring the drug, as is often the case in cancer therapy.
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Toxidermias , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Líquen Plano , Erupções Liquenoides , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Erupções Liquenoides/induzido quimicamente , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Líquen Plano/diagnóstico , Toxidermias/epidemiologia , Toxidermias/etiologia , DemografiaRESUMO
BACKGROUND: Sufficient data on access to systemic treatment for patients with psoriasis living in Latin America (LA) including Brazil and Chile are lacking. Understanding the availability and limiting factors of access to treatments can help to improve patient care and decrease long-term healthcare costs. OBJECTIVES: In association with the Global Psoriasis Atlas, this cross-sectional survey study analysed the availability and insurance reimbursement of systemic treatments for adult patients with psoriasis in Brazil and Chile. METHODS: A multicentre, cross-sectional Global Healthcare Study on Psoriasis was performed in Brazil and Chile in 2020. For each eligible adult patient with psoriasis, doctors and nurses completed a 48-item questionnaire about clinical aspects of psoriasis including the Psoriasis Area Severity Index (PASI), body surface area (BSA) score and the Dermatology Life Quality Index (DLQI), as well as the availability of systemic treatments and insurance reimbursement status. Between-country differences were compared with Wilcoxon rank sum tests for continuous variables, and a χ2-test or Fisher's exact test, where appropriate, for categorical variables. The median and interquartile range (IQR) was calculated for non-normal distributed data. RESULTS: A total of 1424 patients with psoriasis from 43 centres [27 centres in Brazil (n = 826) and 16 in Chile (n = 598)], were included with a mean (SD) age of 49.1 (16.3) and 49.2 (15.1) years, respectively. Unstratified analyses revealed that patients with psoriasis in Chile had more severe disease than those in Brazil [PASI 11.6 vs. 8.4 (P < 0.001) and BSA 14.7 vs. 12.0 (P = 0.003), respectively]. For patients with moderate-to-severe psoriasis, defined as PASI and/or BSA ≥ 10, systemic nonbiologic drugs were available (81.2% in Brazil and 65.3% in Chile, P ≤ 0.001), but only 37.0% of patients in Brazil and 27.3% in Chile received biologics (P = 0.01). Lack of availability and/or lack of insurance reimbursement for biologic drugs for patients with moderate-to-severe psoriasis was reported for 22.2% (50 of 225) in Brazil and 67.9% (148 of 218) in Chile (P < 0.001). Patients with no access to biologic therapies due to lack of availability/insurance reimbursement had a median PASI of 9.15 (IQR 3.00-14.25) in Brazil and 12.0 (IQR 5.00-19.00) in Chile (P = 0.007), as well as a median BSA of 7.0 (IQR 3.00-15.00) and 12.0 (IQR 5.00-22.50) (P = 0.002), and median DLQI of 11.0 (6.00-15.00) and 21.0 (6.50-25.00) (P = 0.007), respectively. CONCLUSIONS: Chilean patients had significantly more severe psoriasis compared with Brazilian patients in our study. While nonbiologic treatments for moderate-to-severe psoriasis were available in both LA countries, there is a high need for improvement in access to more effective psoriasis treatments including biologics. Our results highlight a significant gap between treatment recommendations in international psoriasis guidelines and real-world situations in Brazil and Chile.
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Produtos Biológicos , Psoríase , Adulto , Humanos , Estudos Transversais , Brasil/epidemiologia , Chile/epidemiologia , Qualidade de Vida , Psoríase/tratamento farmacológico , Resultado do Tratamento , Custos de Cuidados de Saúde , Produtos Biológicos/uso terapêutico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Programmed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. METHODS: Multicenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence. RESULTS: In total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD-1 therapies (n = 1003). Twelve-month RFS for anti PD-1 and BRAF + MEK inhibitor-treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335-2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD-1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443-0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p > 0.05). In both, anti PD-1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. CONCLUSIONS: Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk.
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Melanoma , Neoplasias Cutâneas , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Áustria , Suíça , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adjuvantes Imunológicos/uso terapêutico , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Melanoma Maligno CutâneoRESUMO
Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer in Switzerland and worldwide. Most BCCs can be treated in a curative setting. However, patients can develop locally destructive and, rarely, metastatic tumors that require a different treatment approach. The clinical subtype of individual lesions provides prognostic information and influences management decisions. Surgical excision, topical therapies, and radiotherapy are highly effective in the majority of subtypes as well as in low- and high-risk diseases. For patients with low-risk diseases and superficial tumors not amenable to surgery, several nonsurgical alternatives are available. Systemic therapy is indicated for high-risk BCCs, which are not amenable to either surgery or radiotherapy. Hedgehog pathway inhibitors (HHI) are currently approved. Other therapeutic options such as immune checkpoint inhibitors show promising results in clinical trials. This first version of Swiss recommendations for diagnosis and management of BCC was prepared through extensive literature review and an advisory board consensus of expert dermatologists and oncologists in Switzerland. The present guidelines recommend therapies based on a multidisciplinary team approach and rate of recurrence for individual lesions. Based on the risk of recurrence, two distinct groups have been identified: low-risk (easy-to-treat) and high-risk (difficult-to-treat) tumors. Based on these classifications, evidence-based recommendations of available therapies are presented herein.
Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Antineoplásicos/uso terapêutico , Carcinoma Basocelular/terapia , Carcinoma Basocelular/tratamento farmacológico , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/tratamento farmacológico , SuíçaRESUMO
Vitiligo-like depigmentation (VLD) is an immune-related adverse event (irAE) of checkpoint-inhibitor (CPI) treatment, which has previously been associated with a favourable outcome. The aim of this study was to explore clinical, biological and prognostic features of melanoma patients with VLD under CPI-treatment and to explore whether they exhibit a characteristic immune response profile in peripheral blood. Melanoma patients developing VLD under CPI were included in a prospective observational single-center cohort study. We collected and analysed clinical parameters, photographs and serum from 28 VLD patients. They received pembrolizumab (36%), nivolumab (11%), ipilimumab/nivolumab (32%) or clinical trial medications (21%). We performed a high-throughput proteomics assay (Olink), in which we identified a distinct proteomic signature in VLD patients in comparison to non-VLD CPI patients. Our clinical assessments revealed that VLD lesions had a predominantly symmetrical distribution pattern, with mostly smaller "freckle-like" macules and a preferential distribution in UV-exposed areas. Patients with previous targeted therapy showed a significantly longer time lapse between CPI initiation and VLD onset compared to non-pre-treated patients (12.5 vs. 6.25 months). Therapy responders exhibited a distinct proteomic profile when compared with non-responders in VLD such as upregulation of EDAR and downregulation of LAG3. ITGA11 was elevated in the VLD-group when compared to non-VLD-CPI-treated melanoma patients. Our findings demonstrate that on a proteomic level, VLD is characterized by a distinct immune signature when compared to CPI-treated patients without VLD and that therapy responsiveness is reflected by a characteristic immune profile. The pathomechanisms underlying these findings and how they could relate to the antitumoral response in melanoma remain to be elucidated.
RESUMO
BACKGROUND: Psoriasis is a chronic inflammatory skin disease associated with several important medical comorbidities. There are scant data available on the comorbidities of patients with psoriasis in South America. AIM: To examine the comorbidity profile of adult patients with psoriasis in Chile and its association with severity of psoriasis. METHODS: This was a multicentre, cross-sectional study involving 16 hospitals and clinics in Chile, which used a 48-item questionnaire to study clinician- and patient-reported outcomes and comorbidities. Inferential analyses were performed by psoriasis severity, using Fisher exact test, Student t-test and multivariable logistic regression. RESULTS: In total, 598 adult patients with psoriasis were included (51.1% male; mean age 49.2 ± 15.1 years); 48.5% mild and 51.4% moderate to severe; Psoriasis Area and Severity Index 11.6 ± 11.5; body surface area 14.7 ± 18.2%. Plaque psoriasis was the most common phenotype (90.2%), followed by guttate (13.4%). Psoriatic arthritis occurred in 27.3% of patients. Comorbidities were reported in 60.2% of all patients with psoriasis. Frequent concomitant diseases were obesity (25.3%), hypertension (24.3%), Type 2 diabetes mellitus (T2DM) (18.7%), dyslipidaemia (17.4%), metabolic syndrome (16.7%) and depression (14.4%). After adjustment, significant associations were found between moderate to severe psoriasis and obesity, T2DM and nonalcoholic fatty liver disease (NAFLD) compared with mild psoriasis. CONCLUSIONS: We report a large study of comorbidities, including depression, dyslipidaemia, T2DM and NAFLD, in people with psoriasis in Chile. The prevalence of comorbidities with psoriasis in Chile appears similar to that found in Western countries, and emphasizes the importance of assessing patients with psoriasis for risk factors for and presence of, comorbid disease in a multidisciplinary setting.
Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Hepatopatia Gordurosa não Alcoólica , Psoríase , Masculino , Feminino , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Chile/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Transversais , Psoríase/epidemiologia , Comorbidade , Obesidade/epidemiologia , Atenção à SaúdeRESUMO
The exponential increase in algorithm-based mobile health (mHealth) applications (apps) for melanoma screening is a reaction to a growing market. However, the performance of available apps remains to be investigated. In this prospective study, we investigated the diagnostic accuracy of a class 1 CE-certified smartphone app in melanoma risk stratification and its patient and dermatologist satisfaction. Pigmented skin lesions ≥ 3 mm and any suspicious smaller lesions were assessed by the smartphone app SkinVision® (SkinVision® B.V., Amsterdam, the Netherlands, App-Version 6.8.1), 2D FotoFinder ATBM® master (FotoFinder ATBM® Systems GmbH, Bad Birnbach, Germany, Version 3.3.1.0), 3D Vectra® WB360 (Canfield Scientific, Parsippany, NJ, USA, Version 4.7.1) total body photography (TBP) devices, and dermatologists. The high-risk score of the smartphone app was compared with the two gold standards: histological diagnosis, or if not available, the combination of dermatologists', 2D and 3D risk assessments. A total of 1204 lesions among 114 patients (mean age 59 years; 51% females (55 patients at high-risk for developing a melanoma, 59 melanoma patients)) were included. The smartphone app's sensitivity, specificity, and area under the receiver operating characteristics (AUROC) varied between 41.3-83.3%, 60.0-82.9%, and 0.62-0.72% according to two study-defined reference standards. Additionally, all patients and dermatologists completed a newly created questionnaire for preference and trust of screening type. The smartphone app was rated as trustworthy by 36% (20/55) of patients at high-risk for melanoma, 49% (29/59) of melanoma patients, and 8.8% (10/114) of dermatologists. Most of the patients rated the 2D TBP imaging (93% (51/55) resp. 88% (52/59)) and the 3D TBP imaging (91% (50/55) resp. 90% (53/59)) as trustworthy. A skin cancer screening by combination of dermatologist and smartphone app was favored by only 1.8% (1/55) resp. 3.4% (2/59) of the patients; no patient preferred an assessment by a smartphone app alone. The diagnostic accuracy in clinical practice was not as reliable as previously advertised and the satisfaction with smartphone apps for melanoma risk stratification was scarce. MHealth apps might be a potential medium to increase awareness for melanoma screening in the lay population, but healthcare professionals and users should be alerted to the potential harm of over-detection and poor performance. In conclusion, we suggest further robust evidence-based evaluation before including market-approved apps in self-examination for public health benefits.