International exchange on the clinical practice and research of rheumatic skin diseases: A report of the 5th International Conference of Cutaneous Lupus Erythematosus.

The 5th International Conference of Cutaneous Lupus Erythematosus was held in Tokyo, Japan on May 9 and 10, 2023. The latest topics on the pathogenesis, diagnosis, assessment, and treatment of cutaneous lupus erythematosus, dermatomyositis, and scleroderma (systemic sclerosis, morphea) were presented by experts in each field and new developments discussed. In these rheumatic skin diseases, many clinical trials of novel therapies targeting cytokines, signaling molecules, plasmacytoid dendritic cells, B cells, and other molecules are currently underway, and standardization of outcome assessment was discussed. In addition, the selection of the therapeutic agents available for the diversity of each case is becoming more important, together with the ongoing pathophysiological analysis of the diseases. The achievements of this conference will further promote the development of clinical practice and research in rheumatic skin diseases through international exchange among researchers. We hope that by reporting a summary of the conference in this manuscript, we can share its contents with readers.

Patients with autoimmune skin diseases are at increased risk of adverse pregnancy outcomes.

BACKGROUND: Increased rates of adverse pregnancy outcomes have been reported in association with rheumatologic diseases such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis. However, little is known about pregnancy outcomes in patients with autoimmune skin diseases. OBJECTIVE: This study aimed to determine the frequency of adverse pregnancy outcomes in patients with autoimmune skin diseases. We hypothesized that similar to rheumatic diseases, the rate of adverse pregnancy outcomes in patients with autoimmune skin diseases would be higher than the general population. STUDY DESIGN: This is a case control study using the TriNetX US Collaborative Network, which is a database of electronic medical records of >95 million patients seen at 57 healthcare organizations in the United States. All pregnant women between the ages of 15 and 44 years who were seen at a healthcare organization between January 1, 2016 and December 31, 2021 were included. Participants with autoimmune skin disease were matched to healthy controls and controls with systemic rheumatologic conditions (systemic lupus erythematosus or rheumatoid arthritis). For both the autoimmune skin disease and healthy control groups, those with systemic rheumatologic condition or hidradenitis suppurativa were excluded. The primary outcomes were adverse pregnancy outcomes defined as spontaneous abortion, gestational hypertension, preeclampsia or eclampsia, gestational diabetes mellitus, intrauterine growth restriction, preterm premature rupture of membranes, preterm birth, and stillbirth. Patients with autoimmune skin diseases and controls were 1:1 propensity score-matched by age, race, ethnicity, comorbidities, obesity, and substance use. For each outcome, odds ratio with a 95% confidence interval was calculated. RESULTS: A total of 2788 patients with autoimmune skin diseases were matched to 2788 healthy controls. Patients with autoimmune skin diseases were at a higher risk of spontaneous abortions than controls (odds ratio, 1.54; 95% confidence interval, 1.36-1.75; P<.001). Compared with patients with systemic lupus erythematosus, patients with autoimmune skin diseases were at lower risk of having infants with intrauterine growth restriction (odds ratio, 0.59; 95% confidence interval, 0.4-0.87; P=.01), preterm birth (odds ratio, 0.68; 95% confidence interval, 0.47-0.98; P=.04), and stillbirth (odds ratio, 0.50; 95% confidence interval, 0.25-0.97; P=.04). The differences in adverse pregnancy outcomes between patients with autoimmune skin diseases and those with rheumatoid arthritis were not statistically significant. CONCLUSION: Patients with autoimmune skin diseases are at a higher risk of spontaneous abortions than patients without autoimmune skin diseases. When analyzed by each autoimmune skin disease, patients with cutaneous lupus erythematosus or vitiligo remained at increased risk of spontaneous abortions compared with patients without autoimmune skin diseases. Patients with autoimmune skin diseases have similar risks of adverse pregnancy outcomes as patients with rheumatoid arthritis, but lower risks than patients with systemic lupus erythematosus.

Implementation and evaluation of a store-and-forward teledermatology workflow in a United States safety-net hospital urgent care emergency center: A retrospective cohort study.

Background: Teledermatology (TD) is an important method for increasing access to care in outpatient settings. However, less is known regarding its use in emergency/urgent care centers. Objective: To evaluate the effect of TD on urgent care emergency center (UCEC) dwell time and postencounter utilization. Study type and methods: This retrospective cohort study evaluated patients in a safety-net hospital (Parkland Health, Dallas, Texas, USA) UCEC, who (1) received a TD consult in 2018, (2) were referred to dermatology clinic in 2017, or (3) were referred to dermatology clinic in 2018 without a TD consult. Results: We evaluated 2024 patients from 2017 to 2018. Of the 973 referred to dermatology clinic in 2018, 332 (34%) received TD consultations. Mean dwell time for patients receiving TD was longer versus the 2017 cohort (303 vs 204 minutes, respectively). Patients receiving TD consultation with inflammatory skin conditions had lower odds of dermatology clinic visits compared with those that did not (odds ratio, 0.5; 95% CI, 0.3-0.8). Teledermatology was not associated with differences in repeat UCEC utilization. Limitations: Single institution study and inability to account for differences in patient complexity. Conclusion: TD increases dwell time in a safety-net hospital's UCEC but can reduce dermatology clinic utilization for patients with inflammatory skin conditions.

Non-adherence of surgical treatment in patients with non-melanoma skin cancer: a retrospective cohort pilot study.

There is limited data on non-adherence for surgical treatment in non-melanoma skin cancer (NMSC) patients. The objective of this single-center, retrospective cohort study is to compare rates of non-adherence of surgical treatment options, determine factors associated with non-adherence, and identify barriers for non-adherence. All adult patients with NMSC (> 18 years) seen between 2015 and 2017 recommended surgical treatment (surgical excision and electrodessication and curettage (ED&C) or Mohs surgery) were eligible. Non-adherence was defined as not completing recommended treatment and reasons for non-adherence were collected. Out of 427 patients that met inclusion criteria, patients recommended surgical excision and ED&C had a lower non-adherence rate of 3.4% compared to those recommended Mohs (11.4%) (p = 0.006). Factors associated with non-adherence included self-pay patients (19.07% adherent vs. 43.24% non-adherent, p = 0.004). Multivariate logistic regression analysis confirmed that Mohs patients were more likely to be non-adherent (odds ratio (OR) = 3.839, 95% confidence interval (CI) (1.435-10.270), p = 0.007) compared to surgical excision and ED&C patients. Males were more likely to be non-adherent (OR = 2.474, 95% CI (1.105-5.542), p = 0.028) to females, and self-pay patients were more likely to be non-adherent than those with other payers (OR = 3.050, 95% CI (1.437-6.475), p = 0.004). Of the 37 patients who were non-adherent, the most common reasons were loss to follow-up (46%), social reasons (41%), medical reasons (38%), and financial reasons (22%). There was a significant difference in non-adherence rates between surgical treatments for NMSCs in our cohort. Our study suggests the need for future interventional studies that implement strategies and patient education to decrease non-adherence rates.

Late-onset cutaneous lupus erythematosus patients have distinctive clinical features and demographics versus early-onset patients.

BACKGROUND: Cutaneous lupus erythematosus (CLE) can present later in life, but frequency and risk factors of late-onset CLE patients are not well characterized. The study determined frequency of late-onset CLE and compared the demographic and disease characteristics between early-onset and late-onset CLE in a cohort of patients with CLE. OBJECTIVES: To determine the frequency and compare clinical features of early-onset and late-onset CLE. METHODS: This was a cross-sectional study of CLE patients seen in outpatient dermatology clinics at University of Texas Southwestern Medical Center (UTSW) and Parkland Health and Hospital System, Dallas, TX, from April 2009 to May 2019. The primary outcome was the age of CLE onset, stratified by early-onset (<50 years) and late-onset CLE (≥50 years). Predictor variables significantly associated with CLE onset groups were identified by univariate and multivariable logistic regression analyses. RESULTS: Of the 291 CLE patients studied, 79% were early-onset, and 21% were late-onset. Multivariable logistic regression analyses identified that Caucasian race (odds ratio (OR): 2.23, 95% Confidence Interval (CI): 1.19-4.19, p = 0.013), having a CLE subtype other than chronic (OR: 2.18, 95% CI: 1.02-4.65, p = 0.044), and drug-induced cases (OR: 4.65, 95% CI: 1.18-18.24, p = 0.028) were significantly associated with late-onset CLE. Early-onset CLE patients were more likely to have oral ulcers (OR: 3.58, 95% CI: 1.46-8.78, p = 0.005) and renal disorders (OR: 4.02, 95% CI: 1.10-14.71, p = 0.036). LIMITATIONS: This was a single center study. Age of onset was self-reported and late-onset CLE cohort has a small sample size. CONCLUSIONS: Our diverse cohort of CLE patients had about one out of five patients with CLE experiencing disease onset after 50 years old. These patients have distinct demographic and clinical presentations compared to early-onset CLE patients. Providers should remain mindful of CLE in older patients with photosensitive rashes and mild systemic symptoms.

Influence of Socio-Demographic Factors in Patients With Cutaneous Lupus Erythematosus.

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.

The Genetic Landscape of Cutaneous Lupus Erythematosus.

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.

A Systematic Review of the Progression of Cutaneous Lupus to Systemic Lupus Erythematosus.

Lupus erythematosus is an autoimmune disease that may manifest in a variety of organs and tissues including the skin, kidney, brain, heart and lung. Many patients present with cutaneous lupus, where disease is often limited to the skin, but are at risk for developing systemic lupus. The objective of our present study is to perform a systematic review of studies that investigated patient cohorts and populations for the occurrence of cutaneous lupus progressing to systemic lupus. Inclusion criteria required that studies present longitudinal data of patients with limited cutaneous lupus erythematosus who were followed for development of systemic lupus erythematosus. Studies were excluded if patients had concurrent diagnosis of SLE, or if they failed to present longitudinal data. Medline and Embase were searched for English language studies using the Ovid platform. A total of 25 adult studies were identified, as well as 8 pediatric studies. The rate of cutaneous to systemic lupus progression ranged between 0% to 42% in the adult studies and 0% to 31% in the pediatric groups. The variability in these rates were due to differences in patient populations, study design, criteria used to diagnose systemic lupus, and follow-up time. Common risk factors associated with systemic lupus erythematosus development including having positive anti-nuclear antibodies, hematologic abnormalities, and higher number of lupus classification criteria at baseline. This study emphasizes the importance for providers to routinely monitor for systemic lupus in patients with cutaneous lupus.

Black patients with cutaneous lupus are associated with positive family history of cutaneous lupus and systemic lupus.

OBJECTIVES: Various genetic polymorphisms have been associated with an increased risk of cutaneous lupus erythematosus (CLE). However, it is not fully known how often positive family histories occur in patients with CLE. The aims of this study are to determine the rate of positive family history among patients with CLE and to identify risk factors associated with positive family history. METHODS: A retrospective cohort study was conducted among 338 patients with CLE seen in outpatient dermatology clinics in a tertiary referral centre in Dallas, Texas. The primary outcome was positive family history of CLE and/or SLE, as defined by the presence of self-reported CLE and/or SLE in first-degree or more distant relatives of a patient. Univariate analyses were performed to identify risk factors associated with positive family history of CLE and/or SLE in patients with CLE. Multivariable logistic regression analyses were performed to determine significant predictors of positive family history of CLE and/or SLE. RESULTS: 34% (n=114) of patients reported positive family history of CLE and/or SLE. 7% (n=23) of patients with CLE had relatives with CLE, with 5% (n=18) having a first-degree relative with CLE. 30% (n=102) of patients with CLE had relatives with SLE, and 15% (n=52) had a first-degree relative with SLE. Black patients were more likely to have positive family history of CLE and/or SLE (OR 2.13, 95% CI 1.23 to 3.69, p=0.007). CONCLUSIONS: More patients with CLE had positive family history of SLE than CLE. Black patients with CLE were more likely to have a relative with CLE and/or SLE. Providers can use this information to counsel patients with CLE on the risk of other family members having CLE and/or SLE. These data may help identify potentially new genetic polymorphisms associated with positive family history.

Cost minimization analysis of mainstay treatments in cutaneous lupus erythematous.

Cutaneous lupus erythematosus (CLE) can be treated with multiple oral immunosuppressants but cost analyses of these treatments are lacking. We aimed to assess the relative cost difference between various oral medications for CLE using a cost-minimization analysis. Annual direct costs for 10 oral medications used in CLE were calculated including cost of medications and patient monitoring, which include office visits, laboratory and radiological studies, and procedures. Medication costs were taken from the National Average Drug Acquisition Cost calculated by the Centers of Medicare and Medicaid Services or the Average Wholesale Price. Monitoring guidelines were obtained from expert consensus and FDA-approved recommendations. Methotrexate had the lowest total direct cost ($899.31), followed by hydroxychloroquine ($1007.38), mycophenolate mofetil ($1162.12), azathioprine ($1193.71), chloroquine ($2525.01), dapsone ($2750.68), cyclosporine ($2976.32), thalidomide ($75,831.44), and lenalidomide ($316,104.03). For medications used for CLE patients, the medication cost contributes the most to differences between direct costs. Limitations include insufficient patient outcome data to ascertain medication efficacy, exclusion of cost of medication-related adverse events and hospitalizations, and medication cost data not reflecting all payers. Clinicians can use this data to help discern which medication to prescribe CLE patients with financial constraints and reduce healthcare spending.

Cutaneous Lupus Erythematosus and Dermatomyositis: Utilizing Assessment Tools for Treatment Efficacy.

There have been important developments in defining cutaneous lupus erythematosus and dermatomyositis. The skin manifestations of these two diseases have a profound impact on QOL, with both emotional and symptomatic impacts that are important to address. The proliferation of potential therapeutic targets has made it important to make sure that these diseases are defined in a way that they can be included in translational and clinical studies of both localized and systemic forms of the diseases. There are now validated disease tools and QOL studies that are facilitating current and future scientific and therapeutic developments.

Discoid lupus erythematosus skin lesion distribution and characteristics in Black patients: a retrospective cohort study.

OBJECTIVE: Epidemiological studies have shown that discoid lupus erythematosus (DLE) has a higher incidence and prevalence in racial/ethnic minority groups, particularly Black individuals. The objective of this retrospective cohort study was to identify the differences in DLE lesion distribution and characteristics in Black individuals compared with non-Black individuals. METHODS: 183 patients with DLE (112 Black patients and 71 non-Black patients) with a reported race/ethnicity and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores were included in this retrospective cohort study. Univariate analysis was performed to determine significant differences in demographic data, clinical characteristics, DLE lesion distribution and DLE lesion characteristics in Black and non-Black patients with DLE. Multivariable logistic regression was preformed to determine significant predictors of DLE lesion location and characteristics. RESULTS: Black patients with DLE had worse baseline CLASI damage scores compared with non-Black patients with DLE (median (IQR): 10.0 (6.0-14.5) vs 6.0 (3.0-10.0), p<0.001) and had 48.9 greater odds of dyspigmentation in any anatomical location (p<0.001). Black patients had 2.54 greater odds of having scalp involvement (p=0.015) and 1.97 greater odds of having ear involvement (p=0.032) compared with non-Black patients. Black patients also had greater odds of scalp dyspigmentation (OR=5.85, p<0.001), ear dyspigmentation (OR=2.89, p=0.001) and scarring alopecia (OR=3.00, p=0.001) compared with non-Black patients. CONCLUSIONS: Signs of disease damage, particularly ear dyspigmentation, scalp dyspigmentation and scarring alopecia, can more frequently affect Black patients with DLE. Recognising differences in clinical presentation of DLE among Black patients can assist future efforts with understanding biological, cultural, psychosocial and systemic factors that influence DLE presentation and outcomes in Black patients and may guide clinicians when counselling Black patients.