Cutaneous Lupus Erythematosus Patients Research Articles

An update on clinical trials for cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) comprises dermatologic manifestations that may occur independently or with systemic lupus erythematosus (SLE). Despite advancements in refining CLE classification, establishing precise subtype criteria remains challenging due to overlapping presentations and difficulty in distinguishing morphology. Current treatments encompass preventive measures, topical therapies, and systemic approaches. Hydroxychloroquine and glucocorticoids are the sole US Food and Drug Administration (FDA)-approved medications for CLE, with numerous off-label treatments available. However, these treatments are often not covered by insurance, imposing a significant financial burden on patients. The exclusion of most CLE patients, particularly those without concurrent SLE, from trials designed for SLE has resulted in a lack of targeted treatments for CLE. To develop effective CLE treatments, validated outcome measures for tracking patient responsiveness are essential. The Cutaneous Lupus Erythematosus Disease Area and Severity Index is widely utilized for its reliability, validity, and ability to differentiate between skin activity and damage. In contrast, the FDA mandates the use of the Investigator's Global Assessment, a five-point Likert scale related to lesion characteristics, for skin-related therapeutic trials. It requires the disease to resolve or almost completely resolve to demonstrate improvement, which can be difficult when there is residual erythema or incomplete clearance that is meaningfully improved from a patient perspective. Various classes of skin lupus medications target diverse pathways, allowing tailored treatment based on the patient's lupus inflammatory profile, resulting in improved outcomes. Promising targeted therapeutic drugs include anifrolumab (anti-type 1 interferon), deucravacitinib (allosteric tyrosine kinase 2 inhibitor), litifilimab (plasmacytoid dendritic cell-directed therapy), iberdomide (cereblon-targeting ligand), and belimumab (B-cell directed therapy). Despite the significant impact of CLE on quality of life, therapeutic options remain inadequate. While promising treatments for cutaneous lupus are emerging, it is crucial to underscore the urgency for skin-focused treatment outcomes and the implementation of validated measures to assess therapeutic effectiveness in clinical trials.

Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case-control study comparing CLE patients retrospectively assigned to three subgroups based on 3-6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40-80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.

Treatment of Patient with Cutaneous Lupus Erythematosus with Roflumilast Cream 0.3%

Introduction: Cutaneous lupus erythematosus (CLE) is the cutaneous form of a common autoimmune disease, lupus erythematosus, driven by a dysfunction within the adaptive and innate immune system. CLE is subcategorized further into acute, subacute and chronic disease. Here we report a case of a patient with systemic and refractory cutaneous disease with improvement in manifestations demonstrating efficacy following treatment with roflumilast cream 0.3% in a complex chronic CLE patient with uncontrolled disease, intense pruritus and scarring. Case Report: A 48-year-old Asian female with history of smoking, chronic refractory SLE since 2008 with a new onset of pruritic rash. Previous therapies including thalidomide, hydroxychloroquine, methotrexate, mycophenolate mofetil, numerous research trials, oral and intramuscular steroids that failed to control her systemic LE. A Rheumatology colleague referred the patient for new onset cutaneous manifestations. Initial presentation revealed lesions involving 2% of the occipital scalp. Pathology confirmed the diagnosis of discoid lupus. Intralesional triamcinolone , plus topical betamethasone dipropionate 0.05% twice daily (BID) and timolol 0.5% OP solution for wound healing were initiated. Fifteen months later the patient had disease progression of her CLE on to her scalp, face, legs and arms, with the chief complaint of persistent pruritus despite oral prednisone, hydroxychloroquine and thalidomide. The patient’s rheumatologist requested alternative treatment for cutaneous disease without use of long term topical high potency steroids. A second series of intralesional triamcinolone injections plus betamethasone dipropionate 0.05% BID for 3-4 weeks and titrate down to 2-3 applications per week, and addition of roflumilast cream 0.3% was initiated once daily to her face, scalp, and lower legs. On the third office visit, four weeks later, the patient reported pruritus and cutaneous manifestations in lower legs controlled and scalp and face have marked improvement. After 8 weeks on this regimen, the patient return reported that scalp and face continued to improve and disease on the legs continue to be controlled despite not using topical treatment for four weeks. Roflumilast cream 0.3% once daily was continued as monotherapy. Two months later, the patient reported that her skin was fully controlled was starting to repigment with monotherapy. Conclusions: This case report of a 48-year-old female with refractory treatment resistant chronic SLE and CLE treated with roflumilast cream 0.3%, a phosphodiesterase-4 (PDE-4) inhibitor, resulted in disease control, the symptom improvement of improved pruritus as well as repigmentation of the skin. The results observed in this patient suggest this topical intervention, if implemented at the beginning of treatment for cutaneous onset of disease, may have the potential to halt the progression of cutaneous involvement. This case report serves to highlight a promising intervention that may lead to better cutaneous control without long term side effects of topical steroid use.

The development of litifilimab (BIIB 059) for cutaneous and systemic lupus erythematosus.

This review describes the litifilimab (BIIB 059) development program to date for systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). Plasmacytoid dendritic cells (pDCs), major producers of type I interferons (IFN-I), play a key role in SLE pathogenesis. Litifilimab, a humanized monoclonal antibody, binds to BDCA2, a protein uniquely expressed on pDCs. The consequence of BDCA2 ligation is the inhibition of IFN-I as well as IFN-III, cytokine and chemokine production. Phase I and II LILAC trial parts A and B achieved primary end points in SLE and CLE patients, confirming the importance of pDCs and IFN-I in SLE and CLE. Litifilimab is currently being evaluated in phase III trials in both SLE and CLE.

Prevalence, characteristics, and knowledge related to photosensitivity in patients with lupus erythematosus: the international PHOTOLUP study.

To assess the prevalence, characteristics and knowledge about photosensitivity and the use of photoprotective measures in an international cohort of cutaneous and systemic lupus erythematosus patients. We conducted an international, cross-sectional study based on a 46-question web-based survey including patients with medically confirmed LE conducted between November 2021 and April 2022. 600 patients with lupus erythematosus (94% female, median age: 41 years [IQR: 33-51]) from 50 countries were included. A history of photosensitivity was reported by 389/600 (64.8%) patients. Photosensitivity was associated with the presence of other cutaneous involvement (OR = 3.8; 95%CI 2.5-5.7; p < 0.001) and differed according to the area of habits and level of education (p < 0.001, for all). Photosensitivity was characterized by a wide range of clinical manifestations (both cutaneous and systemic symptoms in 56.1% and systemic symptoms only in 29.8% of patients). Fatigue was the most frequently reported systemic manifestation (82.3%). Overall, 559/600 (93%) patients were aware of the detrimental role of UV exposure in lupus erythematosus, but 160/480 (33.3%) were unaware of the importance of photoprotective measures, including 90/310 (29%) among those with photosensitivity. A high rate of self-reported photosensitivity characterize lupus erythematosus patients. Photosensitivity frequently includes subjective features, which makes it difficult to evaluate in clinical practice. As fatigue is frequent in LE, further study is needed to clarify its causal link with UV exposure. About one-third of lupus erythematosus patients are unaware of the importance of photoprotective measures. This should be improved through more frequent and targeted awareness interventions.

Decreased SIRT1 protein may promote HMGB1 translocation in the keratinocytes of patients with cutaneous lupus erythematosus.

Background Ultraviolet radiation causes DNA damage in keratinocytes, aggravating cutaneous lupus erythematosus (CLE). High mobility group box 1 (HMGB1) participates in nucleotide excision and may transfer from the nucleus to the cytoplasm in immune active cells and the translocation of HMGB1 may result in DNA repair defects. HMGB1 was observed to transfer from the nucleus to the cytoplasm in the keratinocytes of CLE patients. As a class III histone deacetylases (HDACs), sirtuin-1 (SIRT1) can induce HMGB1 deacetylation. Epigenetic modification of HMGB1 may lead to HMGB1 translocation. Aims We aimed to evaluate the expressions of SIRT1 and HMGB1 in the epidermis of CLE patients and whether decreased SIRT1 leads to HMGB1 translocation through HMGB1 acetylation in keratinocytes. Methods We measured the messenger RNA (mRNA) and protein expressions of SIRT1 and HMGB1 in CLE patients using real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. Keratinocytes were treated with SIRT1 activator resveratrol (Res) and irradiated with ultraviolet B (UVB). We detected the localization expression of HMGB1 by immunofluorescence. The apoptosis level and the cell cycle proportions were measured by flow cytometry. The acetyl-HMGB1 level was detected by immunoprecipitation. Results Compared to healthy controls, the mRNA and protein expressions of SIRT1 in the epidermis of CLE patients were significantly decreased and there was translocation of HMGB1 from the nucleus to the cytoplasm. In keratinocytes, UVB irradiation led to HMGB1 translocation from the nucleus to the cytoplasm. Res treatment inhibited HMGB1 translocation, attenuated the cell apoptosis induced by UVB and decreased the acetyl-HMGB1 level. Limitations We only treated keratinocytes with the SIRT1 activator but did not perform the relevant experiments in keratinocytes with SIRT1 knockdown or overexpression. In addition, the lysine residue site of action of SIRT1 deacetylation of HMGB1 is unclear. The specific mechanism of action of SIRT1 deacetylation of HMGB1 needs to be further investigated. Conclusion SIRT1 may inhibit HMGB1 translocation by HMGB1 deacetylation which inhibited the apoptosis of keratinocytes induced by UVB. Decreased SIRT1 may promote HMGB1 translocation in the keratinocytes of patients with CLE.

Analysis of Cutaneous Lupus Hospitalizations: A United States National Population-Based Study.

Background There are limited studies analyzing cutaneous lupus erythematosus (CLE)hospitalizations. In this study, we aimed to analyze baseline demographics of systemic lupus erythematosus (SLE) and CLE patients, identify the most common reasons for hospitalizations, and find out the hospitalization outcomes. Materials and methods We performed the analysis using the National (Nationwide) Inpatient Sample (NIS) database between 2016 and 2019. For the CLE cohort, data for adults aged 18 years and older with the primary or secondary diagnosis of CLE using International Classification of Disease - 10th revision (ICD-10) codes were extracted. For comparison, the SLE cohort was identified by patients aged 18 years and older with primary or secondary diagnoses of SLE using ICD-10 codes. Chi-squared testwas used to compare baseline demographic characteristics. Multivariable logistic and linear regression was used to calculate outcomes of interest. Results In comparison to the SLE cohort, the CLE cohort was not only older in age and lower percentage female, but also had shorter length of stay, less total hospital charge, and the majority had Medicare as primary insurance.The SLE cohort included predominantly African American patients while the CLE cohort was majority Caucasian patients. The cardiovascular risks were more prevalent in the CLEcohortand most commonly admitted for sepsis, cardiovascular disease, and mental health disorders. Conclusion Our study highlights the importance of outpatient follow-up in CLE patients to closely monitor cardiovascular risk factors, early identification of infections, and routine mental health screenings to reduce hospitalizations and resource utilization.

New approach for the treatment of autoimmune diseases

Autoimmune diseases are due to a dysregulation of the immune system’s balance, which attacks healthy cells in the body, leading to tissue damage. They can affect different organs/tissues, and the skin represents one of the most affected. Among the skin-related autoimmune diseases, Cutaneous Lupus Erythematosus (CLE) and Morphea are included. Both conditions present various cutaneous manifestations and may also show systemic involvement. It is noted that they can be challenging to treat, often recalcitrant to currently available therapies, thus causing significant distress to affected patients. The approach of personalised medicine, based on regenerative therapies, has been growing in recent years. The use of autologous adult stem cells has successfully treated autoimmune diseases. In this study, we aimed to evaluate the treatment based on patient-specific adipose-tissue stem cells (ASCs) in our two distinct cohorts of patients affected by CLE (n=20) and Morphea (n=12). Patients presenting only with skin lesions underwent local ASCs therapy by intradermal injection in the affected areas. At the same time, patients who also had extra-cutaneous involvement (complicated cases) received a combined therapy consisting of both intradermal and intravenous injections of ASCs. Overall, after 1 month of treatment, an improvement has been observed in 78% and 73% of subjects treated with intradermal injections and combined therapy, respectively. Notably, a better response to ASCs-based therapy has been reported in CLE patients, reaching an 86% in complicated cases. Our study promotes the application of autologous ASCs as an effective therapeutic strategy in skin-related autoimmune diseases.

Epidemiology of Cutaneous Lupus Erythematosus Among Adults Over Four Decades (1976-2018): A Lupus Midwest Network (LUMEN) Study

ObjectiveTo characterize the epidemiological trends and mortality of cutaneous lupus erythematosus (CLE) between 1976 and 2018 in Olmsted County, Minnesota. Patients and MethodsIn this retrospective population-based cohort study, all incident and prevalent CLE cases among adult residents in Olmsted County, Minnesota, between January 1, 1976, and December 31, 2018, were identified and categorized by subtype through medical record review using the resources of the Rochester Epidemiology Project. ResultsThe overall incidence rate of CLE between 1976 and 2018 was 3.9 (95% CI, 3.4 to 4.5) per 100,000. The incidence of CLE was relatively stable, with no major trend across sexes or age groups. The age- and sex-adjusted prevalence of CLE was 108.9 per 100,000 on January 1, 2015. Mortality in CLE patients was similar to that of the general population, with a standardized mortality ratio of 1.23 (95% CI, 0.88 to 1.66) with no observed trends in mortality over time. ConclusionIn the past 4 decades, the incidence of CLE remained stable. Patients with CLE have mortality comparable to that of the general population.

Multidimensional Immune Profiling of Cutaneous Lupus Erythematosus In Vivo Stratified by Patient Response to Antimalarials.

The pathogenesis of cutaneous lupus erythematosus (CLE) is multifactorial, and CLE is difficult to treat due to the heterogeneity of inflammatory processes among patients. Antimalarials such as hydroxychloroquine (HCQ) and quinacrine (QC) have long been used as first-line systemic therapy; however, many patients do not respond to treatment with antimalarials and require systemic immunosuppressants that produce undesirable side effects. Given the complexity and the unpredictability of responses to antimalarial treatments in CLE patients, we sought to characterize the immunologic profile of patients with CLE stratified by subsequent treatment outcomes to identify potential biomarkers of inducible response. We performed mass cytometry imaging of multiple immune cell types and inflammation markers in treatment-naive skin biopsy samples from 48 patients with CLE to identify baseline immunophenotypes that may predict the response to antimalarial therapy. Patients were stratified according to their response to treatment with antimalarials, as HCQ responders, QC responders, or nonresponders. HCQ responders demonstrated increased CD4+ T cells compared to the QC responder group. Patients in the nonresponder group were found to have decreased Treg cells compared to QC responders and increased central memory T cells compared to HCQ responders. QC responders expressed increased phosphorylated stimulator of interferon genes (pSTING) and interferon-κ (IFNκ) compared to HCQ responders. Phosphorylated STING and IFNκ were found to be localized to conventional dendritic cells (cDCs), and the intensity of pSTING and IFNκ staining was positively correlated with the number of cDCs on a tissue and cellular level. Neighborhood analysis revealed decreased regulatory cell interactions in nonresponder patients. Hierarchical clustering revealed that nonresponder patients could be further differentiated based on expression of pSTAT2, pSTAT3, pSTAT4, pSTAT5, phosphorylated interferon regulatory factor 3 (pIRF3), granzyme B, pJAK2, interleukin-4 (IL-4), IL-17, and IFNγ. These findings indicate differential immune cell compositions between patients with CLE, offering guidance for future research on precision-based medicine and treatment response.

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

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. To determine the frequency and compare clinical features of early-onset and late-onset CLE. 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 (<50years) and late-onset CLE (≥50years). Predictor variables significantly associated with CLE onset groups were identified by univariate and multivariable logistic regression analyses. 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). This was a single center study. Age of onset was self-reported and late-onset CLE cohort has a small sample size. Our diverse cohort of CLE patients had about one out of five patients with CLE experiencing disease onset after 50years 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.

High Prevalence of Hypovitaminosis D in Cutaneous and Systemic Lupus Erythematosus Patients and Its Associated Factors: A Cross-Sectional Study in Thailand.

ObjectiveTo investigate the prevalence of low vitamin D levels in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) in Thailand and determine the influential factors associated with inadequate levels.MethodsThe medical records of patients diagnosed with SLE and/or CLE and evaluated for serum 25-OH vitamin D were retrospectively reviewed from January 2014 to January 2021. Vitamin D deficiency (<20 ng/mL) and insufficiency (21–29 ng/mL) were indicated, and predictors of hypovitaminosis D were identified by multiple linear regression analysis.ResultsIn total, 414 patients with SLE and/or CLE were included in the study. Vitamin D deficiency was predominant in the CLE-only group (33.3%), followed by SLE without CLE (15.6%) and SLE with CLE (8%), p < 0.001. Likewise, vitamin D insufficiency was more prevalent in the CLE-only group (44.4%) compared to SLE with (35.8%) and without CLE (40%). Multivariate analysis showed that a higher SLEDAI-2K score and female sex had a negative association with vitamin D levels, while an intake of every 10,000 IU of vitamin D2 per week increased serum vitamin D levels by up to 2.37 ng/mL. Furthermore, forty-five percent of patients continued to have vitamin D depletion despite commencing the recommended doses of vitamin D replacement.ConclusionApproximately half of Thai patients with SLE and 80% of CLE had vitamin D inadequacy. Vitamin D replacement is a good predictor of high serum vitamin D levels, while lower serum levels were associated with higher disease severity. Therefore, serum vitamin D monitoring and supplementation are suggested for all lupus erythematosus cases, especially those with CLE.

IL-33/ST2 Activation Is involved in Ro60-Regulated Photosensitivity in Cutaneous Lupus Erythematosus.

Interleukin- (IL-) 33 contributes to various inflammatory processes. IL-33/ST2 activation participates in systemic lupus erythematous via binding to the receptor of Suppression of Tumorigenicity 2 protein (ST2). However, whether IL-33/ST2 interferes with the nosogenesis of cutaneous lupus erythematosus (CLE) has not been reported so far. Herein, we proposed to disclose the impacts on IL-33/ST2 activation and Ro60 on CLE and their potential implications in the photosensitization of CLE cells. IL-33, ST2, and Ro60 in CLE patients' skin lesions were detected. Murine keratinocytes stimulated with or without IL-33 were irradiated by ultraviolet B (UVB), and the levels of Ro60 and inflammation markers were determined. Keratinocytes were cocultured with J774.2 macrophages and stimulated with IL-33 for analysis of chemostasis. The results identified that IL-33, ST2, and downstream inflammation markers were significantly upregulated in CLE lesions with Ro60 overexpression. Additionally, IL-33 treatment promoted the upregulation of Ro60 induced by UVB treatment in murine keratinocytes. Moreover, IL-33 stimulates keratinocytes to induce macrophage migration via enhancing the generation of the chemokine (C–C motif) ligands 17 and 22. Meanwhile, the silencing of ST2 or nuclear factor-kappa B (NF-κB) suppression abolished IL-33-induced upregulation of Ro60 in keratinocytes. Similarly, the inhibition of SOX17 expression was followed by downregulation of Ro60 in keratinocytes following IL-33 stimulation. In addition, UVB irradiation upregulated SOX17 in keratinocytes. Conclusively, the IL-33/ST2 axis interferes with Ro60-regulated photosensitization via activating the NF-κB- and PI3K/Akt- and SOX17-related pathways.

673 Metabolomic profiling of cutaneous lupus erythematous

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease that disproportionately impacts patients with skin of color. Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune conditions, like CLE, is less well studied. Thus, untargeted liquid chromatography-mass spectrometry metabolomics was performed to characterize the skin and serum of CLE patients. Eleven CLE patients (8 Black and 2 Hispanic Whites) and 14 normal controls were recruited from outpatient dermatology clinics at the University of Texas Southwestern Medical Center and Parkland Health and Hospital System in Dallas, TX.

148 Management of the heightened risk for clinical events from atherosclerotic cardiovascular disease (ASCVD) in an established cohort of lupus erythematosus patients

Lupus erythematosus (LE) patients are at heightened risk of clinical events, chiefly heart attacks and strokes, caused by ASCVD. To address this problem, we recently proposed new guidelines for categorization of levels of risk for ASCVD events in LE patients, with corresponding recommendations for management of conventional risk factors, chiefly hypercholesterolemia, hypertension, smoking, and diabetes mellitus (Keyes E et al. 2021). Here, we performed a single-center study of our established cohort of cutaneous LE patients without or with concurrent systemic LE (n=370).

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.

Increased CD69+CCR7+ circulating activated T cells and STAT3 expression in cutaneous lupus erythematosus patients recalcitrant to antimalarials.

Antimalarials are first-line systemic therapy for cutaneous lupus erythematosus (CLE). While some patients unresponsive to hydroxychloroquine (HCQ) alone benefit from the addition of quinacrine (QC), a subset of patients is refractory to both antimalarials. We classified CLE patients as HCQ-responders, HCQ+QC-responders, or HCQ+QC-nonresponders to compare immune profiles. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to characterize inflammatory cells and cytokines in lesional skin. Immunohistochemistry showed that CD69+ T cells were higher in HCQ+QC-nonresponders compared to HCQ- and HCQ+QC-responders (p < 0.05). Immunofluorescence further identified these cells as CD69+CCR7+ circulating activated T cells. Myeloid dendritic cells were significantly higher in HCQ+QC-responders compared to both HCQ-responders and HCQ+QC-nonresponders. Plasmacytoid dendritic cells were significantly increased in HCQ-responders compared to HCQ- and HCQ+QC-nonresponders. No differences were found in the number of autoreactive T cells, MAC387+ cells, and neutrophils among the groups. CLASI scores of the HCQ+QC-nonresponder group positively correlated with CD69+CCR7+ circulating activated T cells (r = 0.6335, p < 0.05) and MAC387+ cells (r = 0.5726, p < 0.05). IL-17 protein expression was higher in HCQ+QC-responders compared to HCQ-responders or HCQ+QC-nonresponders, while IL-22 protein expression did not differ. mRNA expression demonstrated increased STAT3 expression in a subset of HCQ+QC-nonresponders. An increased number of CD69+CCR7+ circulating activated T cells and a strong correlation with CLASI scores in the HCQ+QC-nonresponders suggest these cells are involved in antimalarial-refractory skin disease. STAT3 is also increased in HCQ+QC-nonresponders and may also be a potential target for antimalarial-refractory skin disease.

Discoid lesions and smoking history are negative predictors of disease activity remission in cutaneous lupus erythematosus

To the Editor: Cutaneous lupus erythematosus (CLE) is a photosensitive skin disorder with a heterogeneous clinical course.1 While it is known that long-term stabilization of disease activity can be achieved on standard therapies, frequencies of remission and recurrence of CLE disease activity are not well studied.2 In this retrospective study, we assessed the rates of disease activity remission and recurrence in a cohort of CLE patients and identified the factors associated with each outcome.

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.

Clinico-Pathological Profile of Cutaneous Lupus Erythematosus Patients: A Report from A Tertiary Care Center of Chattogram

Background : Nearly all epidemiologic studies have involved patients with Systemic Lupus Erythematosus (SLE). Few authors have investigated the characteristics of patients with Cutaneous Lupus Erythematosus (CLE). We aim to describe the epidemiologic, clinical, and immunologic characteristics of a series of patients diagnosed with CLE.&#x0D; Materials and methods : This is a descriptive retrospective cross-sectional study carried out using the register records of total 218 patients attending the ‘Lupus Clinic’ in Chittagong Medical College Hospital during the period 2010 and 2020. The disease activity and damage of CLE were assessed according to the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI).&#x0D; Results : There were 187 females (86%) and 31 males (14%) with the female: male ratio being 6.1:1. The mean age was 28 ± 10.06 (mean ± SD) ranging between 11 and 65 years. The Chronic Cutaneous Lupus Erythematosus (CCLE) patients accounted 154 (71%) followed by Acute Cutaneous Lupus Erythematosus (ACLE) 46 (21%) and Subacute Cutaneous Lupus Erythematosus (SCLE) 18 (8%). On the basis of CLASI score, 91 (42%) patients were in mild form, 85 (39%) in moderate form and 42 (19%) in severe state. In LE specific skin lesions, common manifestation was photosensitivity 198 (91%) followed by discoid rash 154 (71%) and maculo-papular lupus rash 55 (25%). Oral ulcer was seen in 49 (22%) patients and malar rash in 46 (21%) patients. Other observed LE specific skin manifestations were papulo squamous rash 11 (5%), Toxic epidermal necrolysis like lesions 7 (3%) and lichenoid lesions 6 (3%). Among LE nonspecific skin lesions, common manifestation was nonscarring alopecia 123 (56%) followed by Raynaud’s phenomenon 17 (8%) livedo reticularis 17 (8%) Vasculitis 15 (7%) Periungual telangiectasia 7 (3%) erythema multiforme 6 (3%) and leg Ulcer 5 (2%). Antinuclear Antibody (ANA) 132 (61%) was the most common autoantibody followed by anti-ds DNA 91 (42%) anti-Sm antibody 2 (1%) anti-phospholipid antibodies 9 (4%) and anti-RNP 3 (1%). Hematological manifestations were seen in 161 (73.85%) where erythrocyte sedimentation rate was the most common hematological abnormality 161(73.85%) followed by lymphopenia 126 (57.80%) leucopenia 113 (51.80%) thrombocytopenia 107 (49.10%) anemia 92 (42%) monocytopenia 37 (16.97%). Conclusions: CCLE was the most common subtypes of CLE. Patients with different subtypes of CLE have distinct clinical and pathological characteristics. The onset or concurrence of SLE mandates the involvement of other disciplines depending on organ involvement. In the absence of consensus on a definition that makes it possible to differentiate cutaneous forms of LE from SLE, the dermatologist’s role in the correct diagnosis and classification of such patients is fundamental.&#x0D; Chatt Maa Shi Hosp Med Coll J; Vol.20 (2); July 2021; Page 79-84