Cigarette smoking and response to antimalarials in cutaneous lupus erythematosus patients: evolution of a dogma.
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ABSTRACT:
SUBMITTER: Dutz J
PROVIDER: S-EPMC3263354 | biostudies-literature | 2011 Oct
REPOSITORIES: biostudies-literature
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Cigarette smoking and response to antimalarials in cutaneous lupus erythematosus patients: evolution of a dogma.
Dutz Jan J Werth Victoria P VP
The Journal of investigative dermatology 20111001 10
Antimalarial agents ameliorate disease in more than half of patients with cutaneous lupus erythematosus (CLE), regardless of smoking status. The major determinant of responsiveness appears to be severity: more extensive CLE and CLE in the setting of systemic lupus erythematosus (SLE) respond less well to antimalarial therapy. Prospective studies are needed to determine whether antimalarials are more likely to benefit patients--smokers and nonsmokers--who have milder cutaneous lupus. Agreement on ...[more]
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Project description:BackgroundAntimalarial agents (AMs), mainly hydroxychloroquine (HCQ) and chloroquine, are the cornerstone of treatment of cutaneous and systemic lupus erythematosus. However, many aspects of AM prescription remain empirical. The aim of this study was to assess the modalities of AM prescription among physicians treating patients with lupus and to verify the assumption that AM use is heterogeneous and frequently at variance with international guidelines.MethodsWe performed an international cross-sectional study among physicians involved in lupus care, using a web-based survey (from September 2019 to July 2020) addressing the main controversial aspects of AM prescription.ResultsA total of 298 physicians [median age: 42 (interquartile range: 17) years, mainly internists and rheumatologists] from 35 countries participated to the study. A total of 93% used HCQ as the first-line AM, 69.5% used fixed doses of AMs (mainly 400 mg/day for HCQ) and only 37.9% adjusted the dose in case of renal failure. The main reasons for measuring HCQ blood levels were suspected non-adherence (55.7%) and failure of AM treatment (34.1%). In case of AM failure, 58.0% added an immunosuppressive agent. In case of remission, 49.7% maintained the same dose of AM, whereas 48.3% reduced the dose. One-third of respondents reported not following the American screening guidelines on AM retinal toxicity and 40.9% started retinal screening from the first year of treatment.ConclusionThis study highlights the strong heterogeneity of AM prescription in lupus, as well as several key unmet needs regarding AMs. This may be improved by developing more comprehensive recommendations and favoring dissemination among physicians.
| S-EPMC8138289 | biostudies-literature
Project description:BackgroundPrevious studies have suggested that patients with cutaneous lupus erythematosus (CLE) are deficient in sunscreen use. Use of other photoprotective methods by patients with CLE has not been assessed to our knowledge.ObjectiveWe sought to identify demographic and clinical characteristics of patients with CLE who have the lowest overall sun-protection habits scores, and who are least likely to practice 5 individual photoprotective methods (ie, shade, sunscreen, long sleeves, hat, and sunglasses).MethodsA total of 105 patients with CLE at the University of Texas Southwestern Medical Center in Dallas completed a survey to evaluate their photoprotective practices. Additional information including demographics and clinical indicators related to CLE was collected from the patients.ResultsPatients with medium and dark skin (ie, Fitzpatrick skin types III-VI) and patients aged 31 to 50 years were the least likely CLE subgroups to practice overall photoprotection, as indicated by low sun-protection habits scores (P = .001 and P = .04, respectively). In terms of individual photoprotective methods, male patients with CLE were deficient in sunscreen use, but were more likely to wear hats than female patients with CLE. Sunscreen and sunglasses use was also significantly more infrequent in dark-skinned patients than those with Fitzpatrick skin types I to IV. Patients with CLE between the ages of 41 and 50 years were least likely to wear hats.LimitationsThis study was subject to reporter bias and did not cover barriers to and knowledge of photoprotection.ConclusionCultural customs and misconceptions shared by those from the general population have a significant influence on the photoprotective habits of this CLE population. These need to be addressed to improve photoprotection rates in these at-risk individuals.
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Project description:ObjectivesOur study aimed to investigate the effect of cigarette smoking on the clinical phenotype of patients registered in the Chinese Systemic Lupus Erythematosus (SLE) Treatment and Research (CSTAR) group registry database, the first online registry of Chinese patients with SLE.MethodsA prospective cross-sectional study of Chinese SLE patients was conducted using the CSTAR. Our case-control analysis was performed on age- and gender-matched subjects to explore the potential effect of cigarette smoking on the clinical manifestation of SLE.ResultsSmokers comprised 8.9% (65/730) of patients, and the ratio of females/males was 19/46. Thirty-nine patients were current smokers, and 26 were ex-smokers. Data showed significant differences between smokers and nonsmokers in the following areas: nephropathy (58.5% vs. 39.2%; p = 0.003), microscopic hematuria (30.8% vs. 19.1%; p = 0.025), proteinuria (53.8% vs. 34.4%; p = 0.002), and SLE Disease Activity Index(DAI) scores (12.38±8.95 vs. 9.83±6.81; p = 0.028). After adjusting for age and gender, significant differences between smokers and nonsmokers were found with photosensitivity (35.9% vs. 18%; p = 0.006), nephropathy (59.4% vs. 39.8%; p = 0.011), and proteinuria (54.7% vs. 35.2%). Although smokers tended to have greater disease severity compared with nonsmokers (SLEDAI scores: 12.58±8.89 vs.10.5±7.09), the difference was not significant (p = 0.081).ConclusionsCigarette smoking triggers the development and exacerbation of SLE, especially with respect to renal involvement. Chinese smokers with SLE should be advised to discontinue cigarette use.
| S-EPMC4539270 | biostudies-literature
Project description:Purpose of reviewSystemic lupus erythematosus (SLE) is the prototypic autoimmune condition, often affecting multiple organ systems, including the skin. Cutaneous lupus erythematosus (CLE) is distinct from SLE and may be skin limited or associated with systemic disease. Histopathologically, the hallmark of lupus-specific manifestations of SLE and CLE is an interface dermatitis. The cause of SLE and CLE is likely multifactorial and may include shared genetic factors. In this review, we will discuss the genetic findings related to the cutaneous manifestations of SLE and isolated CLE, with a particular focus on the lupus-specific CLE subtypes.Recent findingsSeveral major histocompatibility complex and nonmajor histocompatibility complex genetic polymorphisms have been identified which may contribute to the cutaneous manifestations of SLE and to CLE. Most of these genetic variants are associated with mechanisms attributed to the pathogenesis of SLE, including pathways involved in interferon and vitamin D regulation and ultraviolet light exposure. Although there is overlap between the genetic factors associated with SLE and CLE, there appear to be unique genetic factors specific for CLE.SummaryImproved understanding of the genetics of CLE may lead to the creation of targeted therapies, improving outcomes for patients with this challenging dermatologic condition.
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Project description:Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can occur with or without underlying systemic lupus erythematosus (SLE) and often has a profoundly negative impact on patient quality of life. There is substantial need for new and more effective therapies to treat CLE. CLE has a multifactorial pathogenesis that involves several key immune cells and pathways, including abnormalities in innate (e.g., type 1 interferon pathways) and adaptive immune responses (e.g., B and T cell autoreactivity), presenting multiple opportunities for more targeted therapies that do not require immunosuppression. Here we review several emerging therapies and their efficacy in CLE. Anifrolumab and belimumab have both been approved for the treatment of SLE in recent years, and clinical trial evidence suggests some forms of CLE may improve with these agents. Therapies currently in development that are being evaluated with CLE-specific outcome measures include BIIB059 and VIB7734, which target plasmacytoid dendritic cells (pDCs), and iberdomide, a cereblon modulator. These novel therapies all have previously demonstrated clinical benefit in some forms of CLE. Other therapies which target molecules believed to play a role in CLE pathogenesis, such as Janus kinases (JAKs), spleen tyrosine kinase (SYK), interferon γ (IFNγ), IL-12, and IL-23, have been evaluated in lupus clinical trials with skin-specific outcomes but failed to meet their primary endpoints.
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Project description:Lesional skin biopsies were taken from patients with active, untreated lupus skin disease (chronic discoid lupus erythematosus, CDLE, n=6; subacute cutaneous lupus erythematosus, SCLE, n=5). Healthy control specimens (HC) were obtained from healthy skin of 5 patients undergoing plastic surgery. In every case, two 4mm punch biopsies were taken. One was flash-frozen in liquid nitrogen and afterwards processed for mRNA isolation. The second biopsy was fixed in 5% formalin solution overnight, and was proceeded for histological investigation.The one-color Agilent 60-mer oligo microarray (Agilent, Santa Clara, CA) was used for gene expression analyses. Statistical analyses were performed using the Agilent Feature Extraction Software⢠and the Rosetta Resolver⢠gene expression data analysis system. The presented gene list (Table S1) includes normalized sample/ control log10-ratios (expression > 2-fold enhanced, p<0.01).
2017-02-24 | E-MTAB-5542 | biostudies-arrayexpress
Project description:Objective:The severity and disease course of cutaneous lupus erythematosus (CLE) are highly variable. Consequently, outcome measures for CLE clinical improvement are heterogeneous, complicating treatment decisions and therapeutic development. This study characterises CLE outcome measures and identifies the influence of clinical improvement thresholds on strengths of associations with patient demographic and clinical factors. Methods:In this pilot cohort study, multivariable models identified factors associated with CLE activity and skin damage improvement, defined as relative decreases in Cutaneous Lupus Activity and Severity Index (CLASI) activity (CLASI-A) and damage (CLASI-D) scores, over ranges of response thresholds. Results:66 patients with 119 visit-pairs were included in the CLASI-A analysis. 74 patients with 177 visit-pairs were included in the CLASI-D analysis. Factors associated with CLE activity and damage improvement depended on the response threshold. Some associations were stronger at more stringent thresholds, including subacute CLE predominance with increased likelihood of CLASI-A improvement (R 2=0.73; 50% reduction: OR 1.724 (95% CI 0.537 to 5.536); 75%: 5.67 (95% CI 1.56 to 20.5)) and African-American race with decreased likelihood of CLASI-D improvement (R 2=0.80; 20%: 0.40 (95% CI 0.17 to 0.93); 40%: 0.25 (95% CI 0.08 to 0.82)). Other associations were stable across multiple thresholds, including older age of CLE development with increased likelihood of CLASI-A improvement (R 2=0.25; 50%: 1.05 (95% CI 1.01 to 1.09]; 75%: 1.05 (95% CI 1.00 to 1.10)) and higher initial disease activity with decreased likelihood of CLASI-D improvement (R 2=0.55; 20%: 0.91 (95% CI 0.84 to 0.98); 40%: 0.88 (95% CI 0.79 to 0.97)). Conclusions:Examining a range of CLASI threshold outcomes can comprehensively characterise changes in disease course in patients with CLE. Insufficiently stringent thresholds may fail to distinguish meaningful clinical change from natural fluctuation in disease activity.
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Project description:Cutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disease with potential for systemic involvement, disfigurement, and significant disease burden. The relationships of demographics and socioeconomic status with patients with CLE are emerging topics with important clinical implications. The primary objective of our study is to perform a literature review of studies that have investigated demographic and socioeconomic factors amongst patients with CLE and determine whether these factors influence diagnosis frequency, disease severity and outcomes or health related quality of life. We searched multiple databases to identify literature addressing CLE and concepts such as race, ethnicity, gender, income, education level and geographic location. Information regarding primary research objective was extracted from all full text articles, and a summary of findings was prepared. We found that race and ethnicity can influence CLE diagnosis frequency and disease outcomes. Chronic cutaneous lupus (CCLE) occurs more frequently in Black patients, often with higher overall disease damage. Differences between genders exist in CLE in terms of health-related quality of life, as female gender was a risk factor for worse quality of life in several studies. Lower income, low educational attainment, and lack of health insurance all contribute to poorer overall outcomes in CLE patients. This review will help inform physicians about populations at risk for potentially worse outcomes to guide treatment decisions for patients with CLE and provide important information to design interventions that address modifiable social determinants of health in this population.
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Project description:Cutaneous Lupus Erythematosus (CLE) is a clinically diverse group of autoimmune skin diseases with shared histological features of interface dermatitis and autoantibodies deposited at the dermal-epidermal junction. Various genetic and environmental triggers of CLE promote infiltration of T cells, B cells, neutrophils, antigen presenting cells, and NK cells into lesional skin. In this mini-review, we will discuss the clinical features of CLE, insights into CLE immunopathogenesis, and novel treatment approaches.
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Project description:Cutaneous lupus erythematosus (CLE) is an autoimmune connective tissue disease that can exist as a disease entity or within the context of systemic lupus erythematosus (SLE). Over the years, efforts to elucidate the genetic underpinnings of CLE and SLE have yielded a wealth of information. This review examines prior studies investigating the genetics of CLE at the DNA and RNA level and identifies future research areas. In this literature review, we examined the English language literature captured within the MEDLINE and Embase databases using pre-defined search terms. First, we surveyed studies investigating various DNA studies of CLE. We identified three predominant areas of focus in HLA profiling, complement deficiencies, and genetic polymorphisms. An increased frequency of HLA-B8 has been strongly linked to CLE. In addition, multiple genes responsible for mediating innate immune response, cell growth, apoptosis, and interferon response confer a higher risk of developing CLE, specifically TREX1 and SAMHD1. There was a strong association between C2 complement deficiency and CLE. Second, we reviewed literature studying aberrations in the transcriptomes of patients with CLE. We reviewed genetic aberrations initiated by environmental insults, and we examined the interplay of dysregulated inflammatory, apoptotic, and fibrotic pathways in the context of the pathomechanism of CLE. These current learnings will serve as the foundation for further advances in integrating personalized medicine into the care of patients with CLE.
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