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Kramer K, Pecher AC, Henes J, Klein R. IgE autoantibodies to nuclear antigens in patients with different connective tissue diseases: re-evaluation and novel findings. Front Immunol 2025; 16:1483815. [PMID: 40181984 PMCID: PMC11965355 DOI: 10.3389/fimmu.2025.1483815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 03/04/2025] [Indexed: 04/05/2025] Open
Abstract
Introduction Connective tissue diseases (CTD) are characterised by the overproduction of multiple autoantibodies, especially antinuclear antibodies (ANA) of the IgG type. Meanwhile, also IgE autoantibodies have been described. The aim was therefore, to establish an ELISA for the demonstration of IgE autoantibodies to SSA/Ro, SSB/La, RNP proteins and dsDNA in sera from patients with systemic lupus erythematosus (SLE), Sjoegren's syndrome (SS), and mixed connective tissue disease (MCTD) to investigate their frequency and clinical relevance. Methods Serum samples from 110 patients with SLE, 118 patients with SS, 41 patients with MCTD, and 73 controls were analysed by ELISA for IgE autoantibodies against dsDNA, SSA/Ro52, and SSA/Ro60, SSB/La, and RNP proteins using recombinant antigens. Patients were assessed for different clinical manifestations. Results In SLE and SS, IgE anti-SSA/Ro52-, -SSA/Ro60- and -SSB/La-antibodies showed a significantly higher reactivity than in controls. IgE anti-dsDNA-antibodies were present in 66% of SLE patients. In SLE, there was a correlation of IgE anti-dsDNA- and -anti-SSA/Ro52-antibodies with disease activity and cutaneous manifestation. Neither IgE anti-SSA/Ro- nor -anti-SSB/La-antibodies were associated with distinct clinical manifestations in SS. Also, anti-RNP-antibodies were found to be of the IgE type (up to 90% in MCTD and 70% in SLE). In MCTD, IgE anti-Sm/RNPB- and -anti-RNP68-antibodies correlated with pulmonary manifestations. IgE anti-dsDNA- but not the other IgE autoantibodies decreased under immunosuppressive therapy. Conclusion IgE anti-SSA/Ro-, -SSB/La-, -RNP-, and -dsDNA antibodies show a high frequency and specificity for the prevailing CTD. We confirmed an association of anti-dsDNA and anti-SSA/Ro52 antibodies with disease activity in SLE. In MCTD, there was an association of anti-Sm/RNP B and -RNP68 antibodies with pulmonary disorder.
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Affiliation(s)
| | | | | | - Reinhild Klein
- Department of Haematology, Oncology, Rheumatology, Immunology, University Hospital
Tuebingen, Tuebingen, Germany
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Andrade-Ortega L, Xibillé-Friedmann D, Galarza-Delgado DA, Saavedra MÁ, Alvarez-Nemegyei J, Amigo-Castañeda MC, Fragoso-Loyo H, Gordillo-Huerta MV, Irazoque-Palazuelos F, Jara-Quezada LJ, Merayo-Chalico J, Portela-Hernández M, Sicsik-Ayala S, Abud-Mendoza C, Alpizar-Rodriguez D, Amaya-Estrada JL, Barragán-Navarro YR, Carrillo-Vázquez SM, Castro-Colín Z, Cruz-Álvarez LJ, Durán-Barragán S, Esquivel-Valerio JA, Gamez-Nava JI, García-García C, Gonzalez-Lopez L, Hadid-Smeke J, Hernández-Bedolla A, Hernández-Cabrera MF, Herrera-VanOostdam DA, Horta-Baas G, Iturbide-Escamilla AE, Muñoz-Lopez S, Pacheco-Tena C, Pérez-Cristóbal M, Pimentel-Leon RR, Pinto-Ortiz M, Ramos-Sánchez MA, Sandoval-Cabrera DV, de Anda KS, Silveira LH, Barile-Fabris LA. Clinical Practice Mexican Guidelines for the Treatment of Systemic Lupus Erythematosus: 2024 Update. REUMATOLOGIA CLINICA 2024; 20:490-510. [PMID: 39505612 DOI: 10.1016/j.reumae.2024.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 07/19/2024] [Indexed: 11/08/2024]
Abstract
Herein we present the update for the Mexican Guidelines for the Treatment of Systemic Lupus Erythematosus. It involves the participation of several experts along the country, following the GRADE system. We included aspects regarding vaccines, pregnancy and cardiovascular risk which were not presented in the previous guidelines in 2017.
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Affiliation(s)
- Lilia Andrade-Ortega
- Servicio de Reumatología, Centro Médico Nacional 20 de Noviembre, ISSSTE, CDMX, Mexico.
| | | | - Dionicio A Galarza-Delgado
- Servicio de Reumatología, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Nuevo León, Mexico
| | - Miguel Ángel Saavedra
- División de Investigación en Salud, Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza IMSS, CDMX, Mexico
| | | | | | - Hilda Fragoso-Loyo
- Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencia Médicas y Nutrición, Dr Salvador Zubirán, CDMX, Mexico
| | | | | | - Luis Javier Jara-Quezada
- División de Reumatología, Instituto Nacional de Rehabilitación Dr. Luis Guillermo Ibarra Ibarra, CDMX, Mexico
| | - Javier Merayo-Chalico
- Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencia Médicas y Nutrición, Dr Salvador Zubirán, CDMX, Mexico
| | | | | | - Carlos Abud-Mendoza
- Departamento de Reumatología, Hospital Central "Dr. Ignacio Morones Prieto", Facultad de Medicina de la UASLP, San Luis Potosí, Mexico
| | | | - José Luis Amaya-Estrada
- Servicio de Interna, Hospital Central Sur de Alta Especialidad, Petróleos Mexicanos, CDMX, Mexico
| | | | | | - Zully Castro-Colín
- Servicio de Reumatología, Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza IMSS, CDMX, Mexico
| | | | - Sergio Durán-Barragán
- Departamento de Clínicas Médicas del Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
| | - Jorge A Esquivel-Valerio
- Servicio de Reumatología, Hospital Universitario "Dr. José Eleuterio González", Universidad Autónoma de Nuevo León, Nuevo León, Mexico
| | - Jorge Iván Gamez-Nava
- Intituto de Terapéutica Experimental y Clínica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
| | - Conrado García-García
- Servicio de Reumatología, Hospital General de México "Dr. Eduardo Liceaga", CDMX, Mexico
| | - Laura Gonzalez-Lopez
- Intituto de Terapéutica Experimental y Clínica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
| | - Jaime Hadid-Smeke
- Servicio de Reumatología, Centro Médico Nacional 20 de Noviembre, ISSSTE, CDMX, Mexico
| | | | | | | | - Gabriel Horta-Baas
- Servicio de Reumatología, Hospital General Regional # 1, Instituto Mexicano del Seguro Social, Mérida, Mexico
| | | | - Sandra Muñoz-Lopez
- Servicio de Reumatología, Centro Médico Nacional 20 de Noviembre, ISSSTE, CDMX, Mexico
| | - Cesar Pacheco-Tena
- Facultad de Medicina, Universidad Autónoma de Chihuahua, Chihuahua, Mexico
| | - Mario Pérez-Cristóbal
- Departamento de Reumatología, Hospital de Especialidades del CMN SXXI, IMSS, CDMX, Mexico
| | | | | | | | - Diana V Sandoval-Cabrera
- Servicio de Medicina Interna, Hospital General Regional #2 "Dr. Guillermo Fajardo Ortiz", IMSS, CDMX, Mexico
| | - Karina Santana de Anda
- Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencia Médicas y Nutrición, Dr Salvador Zubirán, CDMX, Mexico
| | - Luis H Silveira
- Departamento de Reumatología, Instituto Nacional de Cardiología Ignacio Chávez, CDMX, Mexico
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3
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Andrade-Ortega L, Xibillé-Friedmann D, Galarza-Delgado DA, Saavedra MÁ, Alvarez-Nemegyei J, Amigo-Castañeda MC, Fragoso-Loyo H, Gordillo-Huerta MV, Irazoque-Palazuelos F, Jara-Quezada† LJ, Merayo-Chalico J, Portela-Hernández M, Sicsik-Ayala S, Abud-Mendoza C, Alpizar-Rodriguez D, Amaya-Estrada JL, Barragán-Navarro YR, Carrillo-Vázquez SM, Castro-Colín Z, Cruz-Álvarez LJ, Durán-Barragán S, Esquivel-Valerio JA, Gamez-Nava JI, García-García C, Gonzalez-Lopez L, Hadid-Smeke J, Hernández-Bedolla A, Hernández-Cabrera MF, Herrera-VanOostdam DA, Horta-Baas G, Iturbide-Escamilla AE, Muñoz-Lopez S, Pacheco-Tena C, Pérez-Cristóbal M, Pimentel-Leon RR, Pinto-Ortiz M, Ramos-Sánchez MA, Sandoval-Cabrera DV, Santana de Anda K, Silveira LH, Barile-Fabris LA. Guías de Práctica Clínica para el tratamiento del lupus eritematoso sistémico del Colegio Mexicano de Reumatología. Actualización 2024. REUMATOLOGÍA CLÍNICA 2024; 20:490-510. [DOI: 10.1016/j.reuma.2024.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Akin G, Akarsu S, Avcı C. How Does Illness Perception Affect the Quality of Life and Sun Protection Behaviors of Rosacea Patients? PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE 2024; 40:e12998. [PMID: 39208246 DOI: 10.1111/phpp.12998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 08/03/2024] [Accepted: 08/12/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Previous studies have noted the link between rosacea severity and quality of life, but there is limited understanding of how disease perception impacts these aspects. Additionally, sun exposure is identified as a common trigger for rosacea flare-ups, emphasizing the importance of sun protection practices in managing the condition. This cross-sectional study aims to fill the gap in the literature by investigating the relationship between clinical severity, disease perception, quality of life, and sun protection behaviors in rosacea patients. METHODS Questionnaires assessing the quality of life, illness perception, sun protection behaviors, sun protection decisional balance, and its potential predictors were completed by 120 rosacea patients and 120 controls. RESULTS Patients exhibited a higher prevalence of sun protection behaviors than the control group (24.15 ± 5.76 vs. 17.63 ± 5.56, p < 0.001) and demonstrated greater determination in adhering to sun protection practices (13.43 ± 2.37 vs. 9.40 ± 3.09, p < 0.001). Hierarchical linear regression analyses showed that quality of life was related to clinical severity, illness perception (consequences, illness coherence, emotional representations), causal attribution (risk factors, immunity), and sun protection decisional balance variables (R2 = 0.45, F = 7.39, p < 0.001). Also, the perceived pros and cons of sun protection behaviors were predicted by illness perception (treatment control), causal attribution (risk factors, immunity, chance/accident), and quality of life variables (R2 = 0.24, F = 2.59, p = 0.004). CONCLUSIONS Providing more information to rosacea patients can improve their disease perception and quality of life, increasing adherence to sun protection behaviors.
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Affiliation(s)
- Gülfem Akin
- Department of Dermatology and Venereology, Faculty of Medicine, Dokuz Eylul University, İzmir, Turkey
| | - Sevgi Akarsu
- Department of Dermatology and Venereology, Faculty of Medicine, Dokuz Eylul University, İzmir, Turkey
| | - Ceylan Avcı
- Department of Dermatology and Venereology, Faculty of Medicine, Dokuz Eylul University, İzmir, Turkey
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Tsoi A, Gomez A, Boström C, Pezzella D, Chow JW, Girard-Guyonvarc'h C, Stamm T, Arnaud L, Parodis I. Efficacy of lifestyle interventions in the management of systemic lupus erythematosus: a systematic review of the literature. Rheumatol Int 2024; 44:765-778. [PMID: 38451302 PMCID: PMC10980639 DOI: 10.1007/s00296-024-05548-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 01/24/2024] [Indexed: 03/08/2024]
Abstract
We performed a systematic review to explore existing evidence regarding the efficacy of lifestyle interventions for the management of systemic lupus erythematosus (SLE). The search was conducted on the 22nd of June 2021 for publications between 1st of January 2000 and the date of search. Additional articles within the aforementioned timeframe and until December 2023 were added by hand searching. Databases utilized were Medline, Embase, Web of Science, and Cinahl. Lifestyle interventions were defined as any intervention encompassing one or more of the following: physical exercise, diet and nutrition, mental health, harmful exposures, sleep, and social relations. The Joanna Briggs Institute critical appraisal tools were used for risk of bias assessment. The search yielded 11,274 unique records, we assessed the full text of 199 records, and finally included 102 studies. Overall, the quality of the evidence is limited, and there were multiple sources of heterogeneity. The two domains most extensively researched were mental health (40 records) and physical exercise (39 records). Psychological interventions had a positive effect on depressive symptoms, anxiety, and health-related quality of life (HRQoL), whereas physical exercise improved fatigue, depressive symptoms, aerobic capacity, and physical functioning. Studies on diet and nutrition (15 records) support that low fat intake and Mediterranean diet may be beneficial for reducing cardiovascular risk, but large interventional studies are lacking. Studies on harmful exposures (7 records) support photoprotection and use of sunscreen. While studies imply benefits regarding disease burden and drug efficacy in non-smokers and regarding HRQoL in normal-weight patients, more survey is needed on tobacco smoking and alcohol consumption, as well as weight control strategies. Studies on social relations (1 record) and sleep (no records) were sparse or non-existent. In conclusion, psychosocial interventions are viable for managing depressive symptoms, and exercise appears essential for reducing fatigue and improving aerobic capacity and physical function. Photoprotection should be recommended to all patients. Lifestyle interventions should be considered a complement, not a substitute, to pharmacotherapy.
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Affiliation(s)
- Alexander Tsoi
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Alvaro Gomez
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Carina Boström
- Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
- Department of Occupational Therapy and Physiotherapy, Karolinska University Hospital, Stockholm, Sweden
| | - Denise Pezzella
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Jun Weng Chow
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Charlotte Girard-Guyonvarc'h
- Division of Rheumatology, Department of Medicine, University Hospital of Geneva and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Tanja Stamm
- Section for Outcomes Research, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
- Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria
| | - Laurent Arnaud
- Department of Rheumatology, Hôpitaux Universitaires de Strasbourg, Centre National de Référence (RESO), INSERM UMR-S 1109, Strasbourg, France
| | - Ioannis Parodis
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
- Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
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Chaisuwannarak K, Rujitharanawong C, Chaiyabutr C, Wongpraprarut C, Silpa-archa N. Dermatologists Should Encourage and Resume Photoprotection in Patients with Photodermatoses and Melasma Following the COVID-19 Pandemic. Clin Cosmet Investig Dermatol 2023; 16:2937-2946. [PMID: 37873511 PMCID: PMC10590580 DOI: 10.2147/ccid.s432108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 10/07/2023] [Indexed: 10/25/2023]
Abstract
Background The COVID-19 pandemic may alter individuals' perspectives and behaviors regarding sun exposure and photoprotection. Presently, there is a paucity of information about how the pandemic influences photoprotection in photodermatoses and melasma. Objective To compare the photoprotection attitudes and behaviors of individuals with photodermatoses and melasma with those of a control group (other dermatologic patients) before and during the COVID-19 pandemic. Methods A questionnaire-based, cross-sectional study was conducted among Thai patients with photodermatoses, melasma, and other dermatological conditions between August 2021 and November 2022. Each of the three groups consisted of 35 patients. Results Among the 105 patients, 81.9% were female, and the mean age was 45.83 years. Over 80% of individuals who used surgical masks daily for 4 to 8 hours believed that these masks provided skin protection from the sun. The duration of sun exposure and the frequency of photoprotection practices decreased significantly in all groups during the COVID-19 pandemic compared to the pre-pandemic period. Sunscreen was the most prevalent form of photoprotection, but its usage declined considerably during the pandemic. Upon physical examination, the photodermatoses and control groups exhibited unchanged skin conditions, while the patients with melasma demonstrated improved skin conditions during the pandemic. Conclusion Owing to increased indoor activities and the perception that face masks could block sunlight, the COVID-19 pandemic led to notable reductions in sun exposure and photoprotective practices. Despite the absence of photodermatoses exacerbation and the observed improvements in patients with melasma, consistent and effective photoprotection must continue to be promoted.
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Affiliation(s)
- Kornkanok Chaisuwannarak
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chuda Rujitharanawong
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chayada Chaiyabutr
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chanisada Wongpraprarut
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Narumol Silpa-archa
- Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Suebsarakam P, Mairiang D. Accuracy and adequacy of photoprotection in pediatric systemic lupus erythematosus patients, and the effect of education on photoprotection: a prospective study. Pediatr Rheumatol Online J 2023; 21:123. [PMID: 37848991 PMCID: PMC10583389 DOI: 10.1186/s12969-023-00901-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Accepted: 09/30/2023] [Indexed: 10/19/2023] Open
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is associated with multiple organ involvement and leads to significant morbidity and mortality. One of the important environmental factors that influences the exacerbation of preexisting SLE is ultraviolet (UV) radiation, so photoprotection is essential. The aims of this study were to evaluate the accuracy and adequacy of photoprotection in pediatric SLE patients, and to investigate the effect of education on photoprotection. METHODS SLE patients aged ≤ 18 years who attended pediatric outpatient clinics were prospectively enrolled. The accuracy and adequacy of photoprotection were assessed by the questionnaire, and compared between baseline and the ≥ 3-month follow-up timepoint. Comprehensive written and verbal photoprotection education was provided to all patients and parents/caregivers after the first assessment. RESULTS One hundred patients were included (mean age 13.6 ± 2.5, 92% female). At the first assessment, 79% of patients used sunscreen with a sunburn protection factor ≥ 30 (77%) and protection grade of ultraviolet A + + + (63%). Fifty-two percent of patients applied sunscreen every day. A minority of patients applied an adequate amount of sunscreen (32%), used water-resistant sunscreen (34%), used lip balm with sunscreen (23%) and reapplied sunscreen when sweating (13%). The most commonly missed areas when applying sunscreen were the ears and dorsum of the feet. The least often practiced sun protection behavior was wearing sunglasses. The most often reported activities during the peak UV index, were playing with friends and walking to the cafeterias. At the second assessment, the majority of photoprotection practices were improved in all aspects except using water-resistant sunscreen, reapplying sunscreen when sweating, applying sunscreen on the ears and dorsum of feet, and wearing sunglasses. The main reason for not using sunscreen switched from thinking it was unnecessary at the first assessment to disliking its texture at the second assessment. CONCLUSIONS Education on photoprotection was effective in improving photoprotection practices. The photoprotection practices that need to be specifically emphasized are applying an adequate amount of sunscreen and using lip balm with sunscreen. The photoprotection which were least practiced at both the first and seconds assessments were reapplying sunscreen when sweating, applying sunscreen on the ears and dorsum of the feet, and wearing sunglasses.
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Affiliation(s)
- Porntipa Suebsarakam
- Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Dara Mairiang
- Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
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Wang DC, Xu WD, Qin Z, Fu L, Lan YY, Liu XY, Huang AF. Systemic lupus erythematosus with high disease activity identification based on machine learning. Inflamm Res 2023; 72:1909-1918. [PMID: 37725103 DOI: 10.1007/s00011-023-01793-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 08/22/2023] [Accepted: 08/28/2023] [Indexed: 09/21/2023] Open
Abstract
OBJECTIVE Clinical evaluation of systemic lupus erythematosus (SLE) disease activity is limited and inconsistent, and high disease activity significantly, seriously impacts on SLE patients. This study aims to generate a machine learning model to identify SLE patients with high disease activity. METHOD A total of 1014 SLE patients with low disease activity and 453 SLE patients with high disease activity were included. A total of 94 clinical, laboratory data and 17 meteorological indicators were collected. After data preprocessing, we use mutual information and multisurf to evaluate and select the importance of features. The selected features are used for machine learning modeling. Performance of the model is evaluated and verified by a series of binary classification indicators. RESULTS We screened out hematuria, proteinuria, pyuria, low complement, precipitation, sunlight and other features for model construction by integrated feature selection. After hyperparameter optimization, the LGB has the best performance (ROC: AUC = 0.930; PRC: AUC = 0.911, APS = 0.913; balance accuracy: 0.856), and the worst is the naive bayes (ROC: AUC = 0.849; PRC: AUC = 0.719, APS = 0.714; balance accuracy: 0.705). Finally, the selection of features has good consistency in the composite feature importance bar plot. CONCLUSION We identify SLE patients with high disease activity by a simple machine learning pipeline, especially the LGB model based on the characteristics of proteinuria, hematuria, pyuria and other feathers screened out by collective feature selection.
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Affiliation(s)
- Da-Cheng Wang
- Department of Evidence-Based Medicine, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China
| | - Wang-Dong Xu
- Department of Evidence-Based Medicine, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China.
| | - Zhen Qin
- Department of Rheumatology and Immunology, Affiliated Hospital of Southwest Medical University, 25 Taiping Road, Luzhou, 646000, Sichuan, China
| | - Lu Fu
- Laboratory Animal Center, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China
| | - You-Yu Lan
- Department of Rheumatology and Immunology, Affiliated Hospital of Southwest Medical University, 25 Taiping Road, Luzhou, 646000, Sichuan, China
| | - Xiao-Yan Liu
- Department of Evidence-Based Medicine, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China
| | - An-Fang Huang
- Department of Rheumatology and Immunology, Affiliated Hospital of Southwest Medical University, 25 Taiping Road, Luzhou, 646000, Sichuan, China.
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Parodis I, Gomez A, Tsoi A, Chow JW, Pezzella D, Girard C, Stamm TA, Boström C. Systematic literature review informing the EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis. RMD Open 2023; 9:e003297. [PMID: 37532469 PMCID: PMC10401222 DOI: 10.1136/rmdopen-2023-003297] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 06/28/2023] [Indexed: 08/04/2023] Open
Abstract
Through this systematic literature review, we assembled evidence to inform the EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). We screened articles published between January 2000 and June 2021. Studies selected for data extraction (118 for SLE and 92 for SSc) were thematically categorised by the character of their intervention. Of 208 articles included, 51 were classified as robust in critical appraisal. Physical activity was the most studied management strategy and was found to be efficacious in both diseases. Patient education and self-management also constituted widely studied topics. Many studies on SLE found psychological interventions to improve quality of life. Studies on SSc found phototherapy and laser treatment to improve cutaneous disease manifestations. In summary, non-pharmacological management of SLE and SSc encompasses a wide range of interventions, which can be combined and provided either with or without adjunct pharmacological treatment but should not aim to substitute the latter when this is deemed required. While some management strategies i.e., physical exercise and patient education, are already established in current clinical practice in several centres, others e.g., phototherapy and laser treatment, show both feasibility and efficacy, yet require testing in more rigorous trials than those hitherto conducted.
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Affiliation(s)
- Ioannis Parodis
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
- Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Alvaro Gomez
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Alexander Tsoi
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Jun Weng Chow
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Denise Pezzella
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Charlotte Girard
- Division of Rheumatology, Department of Medicine, University of Geneva, Geneva, Switzerland
| | - Tanja A Stamm
- Section for Outcomes Research, Medical University of Vienna, Vienna, Austria
- Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Ludwig Boltzmann Gesellschaft, Vienna, Austria
| | - Carina Boström
- Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
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10
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Abstract
Systemic lupus erythematosus (SLE) is a devastating autoimmune disease that can result in substantial morbidity and mortality. Diagnosis and treatment of SLE are clinical challenges. Patient presentation and response to therapy are heterogeneous because of the complex immune dysregulation that results in SLE disease pathogenesis. An intricate interplay between genetic risk and skewing of adaptive and innate immune system responses leads to overproduction of type I interferons and other cytokines, complement activation, immune-complex deposition, and ultimately inflammation and tissue damage. Here, we review the classification criteria as well as standard and emerging diagnostic tools available to identify patients with SLE. We then focus on medical management, including novel therapeutics, nonpharmacologic interventions, and comorbidity management.
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Affiliation(s)
- Stephanie Lazar
- Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA;
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11
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Koumaki D, Papadakis M, Kouloumvakou S, Krasagakis K. Awareness, knowledge, and attitudes towards sun protection among patients with melanoma and atypical mole syndrome. World J Clin Oncol 2022; 13:587-598. [PMID: 36157160 PMCID: PMC9346423 DOI: 10.5306/wjco.v13.i7.587] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/18/2022] [Accepted: 06/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients with atypical mole syndrome (AMS) have a 3- to 20-fold higher risk of developing malignant melanoma (MM) than individuals without. The most modifiable risk factor for developing MM is the ongoing ultraviolet exposure. AIM To assess awareness, knowledge, and attitudes towards sun protection among patients with MM and AMS. METHODS From January 2020 till December 2021, a written survey was administered to patients with MM and AMS and a control group who attended a specialist mole clinic at the Dermatology Department of the University Hospital of Heraklion in Heraklion, Crete, Greece. Demographic data and photoprotective practices, knowledge, and perceived barriers were collected. Relevant statistical analyses were performed using SPSS IBM 25. RESULTS In total, 121 subjects consented and participated in the survey. Their mean age was 43.92 ± 12.55 years. There were 66 (54.4%) females and 55 (45.4%) males. Forty-seven (38.8%) patients had AMS, 26 (21.5%) had a past medical history of MM, and 48 (39.7%) attended the clinic for a full skin checkup for their naevi without having AMS or MM. Although 104 (86%) participants reported using sunscreen with the majority of them (59/121 = 48.8%) wearing sunscreen with a sun protection factor of > 50, only 22 (18.2%) patients did so every day and only 20 (16.5%) all year round. Approximately 74.4% of patients recalled having received advice on how to protect their skin from sunlight, and 73% were interested in receiving education about sun protection. The most mentioned barriers in photoprotection were concerns over adequate vitamin D and lack of time. CONCLUSION Despite mentioning having received adequate education in photoprotection, adherence to photoprotection practices is suboptimal in patients with MM and AMS.
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Affiliation(s)
- Dimitra Koumaki
- Department of Dermatology, University Hospital of Heraklion, Heraklion 71110, Greece
| | - Marios Papadakis
- Department of Surgery II, University of Witten-Herdecke, Wuppertal 42283, Germany
| | - Stamatoula Kouloumvakou
- Department of Internal Medicine, Agios Nikolaos General Hospital, Agios Nikolaos 72100, Greece
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12
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Li M, Zhao Y, Zhang Z, Huang C, Liu Y, Gu J, Zhang X, Xu H, Li X, Wu L, Song Y, Li X, Jin H, Lei J, Chen Y, Zeng X, Chinese Rheumatology Association, National Clinical Research Center for Dermatologic and Immunologic Diseases, Chinese Systemic Lupus Erythematosus Treatment and Research Group. 2020 Chinese Guidelines for the Diagnosis and Treatment of Systemic Lupus Erythematosus. RHEUMATOLOGY AND IMMUNOLOGY RESEARCH 2020; 1:5-23. [PMID: 36465077 PMCID: PMC9524765 DOI: 10.2478/rir-2020-0009] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 08/12/2020] [Indexed: 02/05/2023]
Abstract
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that represents a prodigious challenge of diagnosis and treatment. In 2019, under the leadership of the Chinese Rheumatology Association, a multidisciplinary guideline development group was established to develop an evidence-based diagnosis and treatment guideline for patients with SLE in PR China. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of evidence and the strength of recommendations. The guideline was reported following the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. In this guideline, we provided recommendations for SLE classification criteria, disease activity monitoring and assessment, medication administration and considerations for SLE patients with organs and systems involved, and management of special populations such as SLE patients in the setting of pregnancy. This guideline serves as an evidence-based tool for Chinese clinicians to diagnose and treat patients with SLE.
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Affiliation(s)
- Mengtao Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Yan Zhao
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Zhiyi Zhang
- Department of Rheumatology, the First Affiliated Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Cibo Huang
- Department of Rheumatology, Beijing Hospital, Beijing, China
| | - Yi Liu
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Jieruo Gu
- Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Xiao Zhang
- Guangdong Provincial General Hospital, Guangzhou, Guangdong Province, China
| | - Huji Xu
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China
| | - Xiaofeng Li
- Department of Rheumatology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
| | - Lijun Wu
- Department of Rheumatology, Xinjiang Uygur Autonomous Region People's Hospital, Urumuqi, Xinjiang Uygur Autonomous Region, China
| | - Yijun Song
- Department of Gynecology and Obstetrics, Peking Union Medical College, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xuemei Li
- Department of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Hongzhong Jin
- Department of Dermatology, Peking Union Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Junqiang Lei
- Department of Radiology, the First Hospital of Lanzhou University, Lanzhou, Gansu Province, China
| | - Yaolong Chen
- Lanzhou University Evidence-based Medicine Center/Chinese GRADE Center, Lanzhou, Gansu Province, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Chinese Rheumatology Association, National Clinical Research Center for Dermatologic and Immunologic Diseases, Chinese Systemic Lupus Erythematosus Treatment and Research Group
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
- Department of Rheumatology, the First Affiliated Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang Province, China
- Department of Rheumatology, Beijing Hospital, Beijing, China
- Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
- Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
- Guangdong Provincial General Hospital, Guangzhou, Guangdong Province, China
- Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China
- Department of Rheumatology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China
- Department of Rheumatology, Xinjiang Uygur Autonomous Region People's Hospital, Urumuqi, Xinjiang Uygur Autonomous Region, China
- Department of Gynecology and Obstetrics, Peking Union Medical College, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Department of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Department of Dermatology, Peking Union Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Department of Radiology, the First Hospital of Lanzhou University, Lanzhou, Gansu Province, China
- Lanzhou University Evidence-based Medicine Center/Chinese GRADE Center, Lanzhou, Gansu Province, China
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13
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Chanprapaph K, Ploydaeng M, Pakornphadungsit K, Mekwilaiphan T, Vachiramon V, Kanokrungsee S. The behavior, attitude, and knowledge towards photoprotection in patients with cutaneous/systemic lupus erythematosus: a comparative study with 526 patients and healthy controls. Photochem Photobiol Sci 2020; 19:1201-1210. [PMID: 32935699 DOI: 10.1039/d0pp00073f] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
OBJECTIVE To evaluate the attitude, knowledge, and behavior towards the sun protection in systemic lupus erythematosus (SLE) patients with and without cutaneous involvement (CLE) compared to non-photosensitive controls and to determine influential factors for photoprotective practices in SLE patients. METHODS A case-control study was performed. Patients and controls completed a self-reported questionnaire. For SLE patients, the presence of organ involvement, disease activity and laboratory data were acquired from their physical examination and medical records. RESULTS A total of 263 SLE patients and 263 healthy controls were recruited. SLE patients had statistically significant better photoprotective practices than controls, i.e. exposure to sunlight <1 hour per day (76.1% vs. 48.3%, OR, 3.40; 95% CI, 2.34-4.93, p < 0.001), less outdoor activities (9.8% vs. 19.1%, OR, 0.44; 95% CI, 0.26-0.71, p = 0.003), wore long-sleeved shirts (57.0% vs. 32.7%, OR, 2.73; 95% CI, 1.92-3.89, p < 0.001) and hats (43.8% vs. 26.6%, OR 2.14; 95% CI, 1.49-3.09, p < 0.001). SLE with CLE subgroup had the highest percentage for regular practice in almost all sun protective means compared to SLE without CLE and controls. SLE with CLE patients had more diligent sunscreen application with higher percentage of consistent use (93.7% vs. 59.3%, OR, 11.66; 95% CI, 2.57-52.89, p = 0.001) and adequate application (58.1% vs. 24.6%, OR, 4.24; 95% CI, 1.93-9.30, p < 0.001) compared to those without CLE. Previous and current CLE were influential factors for adherence to photoprotective methods, while the extracutaneous involvement was not. The majority of SLE patients were well acquainted with the harm of sunlight to their diseases (91.6%). However, 40.1% of them did not perceive that sunlight could escalate their internal flare, which may have led to inferior photoprotective practices in patients with extracutaneous involvement. CONCLUSION SLE patients had good awareness and practiced better photoprotection than controls. The cutaneous sign is a predictor for superior photoprotective behavior. Education regarding the harms of sunlight and the importance of appropriate photoprotection should be emphasized, especially in SLE cases without cutaneous involvement.
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Affiliation(s)
- Kumutnart Chanprapaph
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama IV Rd, 10400, Bangkok, Thailand
| | - Monthanat Ploydaeng
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama IV Rd, 10400, Bangkok, Thailand
| | - Kallapan Pakornphadungsit
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama IV Rd, 10400, Bangkok, Thailand
| | - Thiraphong Mekwilaiphan
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama IV Rd, 10400, Bangkok, Thailand
| | - Vasanop Vachiramon
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama IV Rd, 10400, Bangkok, Thailand
| | - Silada Kanokrungsee
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama IV Rd, 10400, Bangkok, Thailand.,Skin Center Srinakharinwirot University, 114 Sukhumvit 21, 10110, Bangkok, Thailand
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14
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Janthongsri T, Wisuthsarewong W, Nitiyarom R. Photoprotective habits in children with systemic lupus erythematosus. Lupus 2020; 29:964-969. [PMID: 32517570 DOI: 10.1177/0961203320930098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can involve multiple organ systems. Exposure to ultraviolet radiation (UVR) can exacerbate pre-existing SLE, and can even induce systemic manifestations. This study aimed to investigate the photoprotective habits of children with SLE and the factors that significantly influence those photoprotective habits. METHODS This questionnaire-based cross-sectional study included paediatric SLE patients being treated at the Department of Paediatrics at Siriraj Hospital, Mahidol University, between September 2018 and September 2019. Data were obtained from medical records and a face-to-face interview. RESULTS Ninety-six patients were enrolled, with a female-to-male ratio of 8:1. The mean age of patients at enrollment was 13.7 ± 2.4 years. Of the 96 patients, 70 (72.9%) reported being directly exposed to sunlight for less than two hours per day, but 39% of patients spent time in the sun during the peak hours of UVR. Up to 95% of patients used sunscreen. However, only 64% of patients applied it every day, and only 35% of patients used an adequate amount of sunscreen. Girls were significantly more likely to apply sunscreen every day than boys were (p = 0.041). SLE patients with a shorter disease duration had significantly greater exposure to sunlight than patients with a disease duration of more than four years (p = 0.040). CONCLUSION Sunscreen was the most common photoprotective method. However, most patients used sunscreen inappropriately. A shorter disease duration was significantly associated with more sunlight exposure. Regular evaluation and emphasis of the importance of photoprotection should be encouraged among paediatric SLE.
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Affiliation(s)
- Tipusa Janthongsri
- Division of Dermatology, Department of Paediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Wanee Wisuthsarewong
- Division of Dermatology, Department of Paediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Rattanavalai Nitiyarom
- Division of Dermatology, Department of Paediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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15
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Abstract
Lupus nephritis (LN) is a form of glomerulonephritis that constitutes one of the most severe organ manifestations of the autoimmune disease systemic lupus erythematosus (SLE). Most patients with SLE who develop LN do so within 5 years of an SLE diagnosis and, in many cases, LN is the presenting manifestation resulting in the diagnosis of SLE. Understanding of the genetic and pathogenetic basis of LN has improved substantially over the past few decades. Treatment of LN usually involves immunosuppressive therapy, typically with mycophenolate mofetil or cyclophosphamide and with glucocorticoids, although these treatments are not uniformly effective. Despite increased knowledge of disease pathogenesis and improved treatment options, LN remains a substantial cause of morbidity and death among patients with SLE. Within 10 years of an initial SLE diagnosis, 5-20% of patients with LN develop end-stage kidney disease, and the multiple comorbidities associated with immunosuppressive treatment, including infections, osteoporosis and cardiovascular and reproductive effects, remain a concern. Clearly, early and accurate diagnosis of LN and prompt initiation of therapy are of vital importance to improve outcomes in patients with SLE.
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16
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Traboulsi D, Potok OV, Ruzycki SM, Surmanowicz P, Hardin J, Khokhar B, Rabi DM, Hazlewood G, Mydlarski PR. Skin cancer knowledge and photoprotective practices of organ transplant recipients. Clin Transplant 2019; 33:e13524. [DOI: 10.1111/ctr.13524] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 02/11/2019] [Accepted: 02/20/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Danya Traboulsi
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
| | - Olivia V. Potok
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
| | - Shannon M. Ruzycki
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
| | - Philip Surmanowicz
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
| | - Jori Hardin
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
| | - Bushra Khokhar
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
| | - Doreen M. Rabi
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
| | - Glen Hazlewood
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
- Department of Community Health Sciences, Cumming School of Medicine University of Calgary Calgary Alberta Canada
| | - Paule Régine Mydlarski
- Department of Medicine, Cumming School of Medicine University of Calgary Calgary Alberta Canada
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