Search

Purpose of Review: Epithelial cells have been acknowledged as important players in autoimmune diseases by directing and enhancing inflammatory responses. Here, we summarize recent publications that examine keratinocyte (KC) dysfunction and its contribution to cutaneous and systemic disease in systemic lupus erythematosus patients. Recent Findings: Chronic upregulation of type I interferon (IFN) in KCs is a feature of both lesional and nonlesional lupus skin. This IFN rich environment modulates epidermal cell death responses and promotes inflammatory responses to UV light exposure. In addition, newer technologies such as single cell RNA-seq are informing our understanding of lupus-specific intercellular crosstalk and how this contributes to disease. Summary: Recent discoveries in KC dysfunction in lupus skin include aberrant IFN responses to environmental stress, enhanced cytokine and chemokine secretion and epigenetic changes leading to increased cell death. Further research will enable precision therapies for lupus treatment. [ABSTRACT FROM AUTHOR]

Acute cutaneous lupus erythematosus (ACLE) is closely associated with systemic symptoms in systemic lupus erythematosus (SLE). This study aimed to identify potential biomarkers for ACLE and explore their association with SLE to enable early prediction of ACLE and identify potential treatment targets for the future. In total, 185 SLE‐diagnosed patients were enrolled and categorized into two groups: those with ACLE and those without cutaneous involvement. After conducting logistic regression analysis of the differentiating factors, we concluded that tumor necrosis factor‐alpha (TNF‐α) is an independent risk factor for ACLE. Analysis of the receiver operating characteristic revealed an area under the curve of 0.716 for TNF‐α. Additionally, both TNF‐α and ACLE are positively correlated with disease activity. TNF‐α shows promise as a biomarker for ACLE, and in SLE patients, ACLE may serve as a clear indicator of moderate‐to‐severe disease activity. [ABSTRACT FROM AUTHOR]

The array of potential differential diagnoses of cutaneous lupus erythematosus (CLE) is extensive. Exclusion of infection is paramount, given the patient’s immunodeficient state. We report the case of a 33-year-old female patient who presented with pruritic erythematous papules across her upper extremities, originally presumed to be a drug eruption. Cutaneous xerosis and desquamation involving the hands were also noted, concomitant with diffuse hair loss and onychodystrophy. Potassium hydroxide and culture analysis from nail scrapings aligned with onychomycosis. Concurrently, histopathological assessment of the skin biopsy illustrated subacute CLE. Following the completion of the antifungal, mycophenolate mofetil was initiated, owing to suboptimal outcomes observed with the previous treatment modalities. The resolution of scaling on the scalp was concomitant with the emergence of new hair growth. Alopecia in lupus erythematosus patients mandates a thorough examination, owing to the extensive spectrum of its potential causes. Involvement of the nails mandates a rigorous exclusion of infections.

Tumid lupus erythematosus is an uncommon subtype of chronic cutaneous lupus erythematosus. Hereby, we report a 36-year-old male patient with tumid lupus erythematosus who presented with erythematous papules and plaques on the face and neck who showed significant improvement after treatment with topical tacrolimus and topical hydrocortisone 17-butyrate.

Abstract Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by loss of tolerance to nuclear antigens. The formation of autoantibodies and the deposition of immune complexes trigger inflammatory tissue damage that can affect any part of the body. In most cases, SLE is a complex disease involving multiple genetic and environmental factors. Despite advances in the treatment of SLE, there is currently no cure for SLE and patients are treated with immunosuppressive drugs with significant side effects. The elucidation of rare monogenic forms of SLE has provided invaluable insights into the molecular mechanisms underlying systemic autoimmunity. Harnessing this knowledge will facilitate the development of more refined and reliable biomarker profiles for diagnosis, therapeutic monitoring, and outcome prediction, and guide the development of novel targeted therapies not only for monogenic lupus, but also for complex SLE.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a multifactorial etiology in which genetic and environmental factors interplay. An exclusively cutaneous condition has been described and defined as cutaneous lupus erythematosus (CLE). In Italy, a nationwide blood donor survey found an overall HEV prevalence of 8.7%, with an interregional variation from 2.2% to 22.8%. In this study, we aimed to estimate HEV seroprevalence in a cohort of patients affected by SLE and CLE attending the Lupus Clinic, Sapienza University of Rome. Serum samples were tested for anti-HEV immunoglobulin Ig G and M antibodies using commercial enzyme-linked immunosorbent assay (ELISA) kits. Statistical analysis was performed. In total, 138 patients were enrolled, 92 (67%) affected by SLE and 46 by CLE. The prevalence of HEV infection was 23.9% in the CLE group and 7.6% in the SLE group. The anti-HEV+ prevalence was significantly more frequent in CLE. Some mechanisms may be linked to increased susceptibility to HEV such as a molecular mimicry associated with the CLE condition or with the skin compartment/skin self-antigens, as well as the involvement of the genetic background. Regarding the possible risk factors, no association was found, although, of note, the odds of HEV+ relative to contact with animals and to eating raw seafood were strongly higher than the unit in the CLE group. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by loss of tolerance to nuclear antigens. The formation of autoantibodies and the deposition of immune complexes trigger inflammatory tissue damage that can affect any part of the body. In most cases, SLE is a complex disease involving multiple genetic and environmental factors. Despite advances in the treatment of SLE, there is currently no cure for SLE and patients are treated with immunosuppressive drugs with significant side effects. The elucidation of rare monogenic forms of SLE has provided invaluable insights into the molecular mechanisms underlying systemic autoimmunity. Harnessing this knowledge will facilitate the development of more refined and reliable biomarker profiles for diagnosis, therapeutic monitoring, and outcome prediction, and guide the development of novel targeted therapies not only for monogenic lupus, but also for complex SLE. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess the prevalence and characteristics of, and knowledge about, photosensitivity and the use of photoprotective measures in an international cohort of cutaneous lupus erythematosus and SLE patients. Methods We conducted an international, cross-sectional study based on a 46-question web-based survey, including patients with medically confirmed lupus erythematosus, conducted between November 2021 and April 2022. Results A total of 600 patients with lupus erythematosus [94% female, median age: 41 years, interquartile range (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 [odds ratio (OR) = 3.8; 95% CI 2.5–5.7; P  < 0.001] and differed according to the area of residence 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 ultraviolet radiation 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. Conclusion A high rate of self-reported photosensitivity characterizes lupus erythematosus patients. Photosensitivity frequently includes subjective features, which makes it difficult to evaluate in clinical practice. As fatigue is frequent in lupus erythematosus, further study is needed to clarify the causal link with ultraviolet radiation 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. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the prevalence of skin disease among patients with systemic lupus erythematosus (SLE) and determine whether LE skin disease had clinical or serologic correlates with SLE. Methods: We reviewed records of 335 patients with SLE (seen at Mayo Clinic, Rochester, Minnesota, USA) and abstracted skin manifestations, fulfilled mucocutaneous SLE criteria, and clinical and serologic parameters. Results: Of the 231 patients with skin manifestations, 57 (24.7%) had LE‐specific conditions, 102 (44.2%) had LE‐nonspecific conditions, and 72 (31.2%) had both. LE skin disease was associated with photosensitivity, anti‐Smith antibodies, and anti‐U1RNP antibodies (all P < 0.001). Patients without LE skin disease more commonly had elevated C‐reactive protein levels (P = 0.01). Patients meeting 2–4 mucocutaneous American College of Rheumatology criteria less commonly had cytopenia (P = 0.004) or anti−double‐stranded DNA antibodies (P = 0.004). No significant associations were observed for systemic involvement (renal, hematologic, neurologic, and arthritis) when comparing patients with or without LE skin involvement. LE skin involvement was not significantly associated with internal SLE disease flare, number of medications, or overall survival. Conclusions: LE skin disease commonly occurs in patients with SLE. The presence of LE skin disease had no mitigating impact on the severity of SLE sequelae, disease flares, number of medications, or overall survival. Plain language summary: Skin manifestations of systemic lupus erythematosus (SLE) are myriad and can have a dramatic impact on patients' lives. Our study at Mayo Clinic, Rochester/Minnesota, USA, investigated the range of skin disease that occurs in patients with SLE and showed that these skin manifestations require as much systemic treatment comparable to those used for other organs affected by SLE in patients without skin findings. Patients with skin manifestations did not have better survival than those without skin manifestations. Our study highlights the important role of dermatologists in the care of patients with SLE and in SLE research. [ABSTRACT FROM AUTHOR]

Tumid lupus erythematosus is an uncommon subtype of chronic cutaneous lupus erythematosus. Hereby, we report a 36-year-old male patient with tumid lupus erythematosus who presented with erythematous papules and plaques on the face and neck who showed significant improvement after treatment with topical tacrolimus and topical hydrocortisone 17-butyrate. [ABSTRACT FROM AUTHOR]

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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Lupus erythematosus tumidus is an uncommon disorder characterized by erythematous urticarial non-scarring plaques. It has high photosensitivity and a clinical course with relapses and spontaneous remission. Histologic features include perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition, with the absence of changes on the epidermal surface. We present the case of a 55-year-old male who presented with an erythematous urticarial plaque on the forehead. Initially, we consider Hansen's disease due to its prevalence and regional epidemiology. [ABSTRACT FROM AUTHOR]

The array of potential differential diagnoses of cutaneous lupus erythematosus (CLE) is extensive. Exclusion of infection is paramount, given the patient's immunodeficient state. We report the case of a 33-year-old female patient who presented with pruritic erythematous papules across her upper extremities, originally presumed to be a drug eruption. Cutaneous xerosis and desquamation involving the hands were also noted, concomitant with diffuse hair loss and onychodystrophy. Potassium hydroxide and culture analysis from nail scrapings aligned with onychomycosis. Concurrently, histopathological assessment of the skin biopsy illustrated subacute CLE. Following the completion of the antifungal, mycophenolate mofetil was initiated, owing to suboptimal outcomes observed with the previous treatment modalities. The resolution of scaling on the scalp was concomitant with the emergence of new hair growth. Alopecia in lupus erythematosus patients mandates a thorough examination, owing to the extensive spectrum of its potential causes. Involvement of the nails mandates a rigorous exclusion of infections. [ABSTRACT FROM AUTHOR]

Antimalarials (AMs), particularly hydroxychloroquine (HCQ) and chloroquine (CQ), are the cornerstone of the treatment for both systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE). HCQ and CQ are recommended as first‐line oral agents in all CLE guidelines. Initially thought to have potential therapeutic effects against COVID‐19, HCQ has drawn significant attention in recent years, highlighting concerns over its potential toxicity among patients and physicians. This review aims to consolidate current evidence on the efficacy of AMs in CLE. Our focus will be on optimizing therapeutic strategies, such as switching from HCQ to CQ, adding quinacrine to either HCQ or CQ, or adjusting HCQ dose based on blood concentration. Additionally, we will explore the potential for HCQ dose reduction or discontinuation in cases of CLE or SLE remission. Our review will focus on the existing evidence regarding adverse events linked to AM usage, with a specific emphasis on severe events and those of particular interest to dermatologists. Last, we will discuss the optimal HCQ dose and the balance between preventing CLE or SLE flares and minimizing toxicity. [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) may present as an isolated entity or be classified as Systemic lupus erythematosus (SLE) by the presence of laboratory abnormalities, including cytopenia, low complement levels, and/or autoantibodies (CLE with laboratory SLE). To compare isolated CLE and CLE with laboratory SLE and to validate an existing 3-item score with age < 25 years (1 point), phototypes V to VI (1 point), antinuclear antibodies ≥ 1:320 (5 points) to predict the risk of progression from CLE to severe SLE (sSLE). Monocentric cohort study including consecutive patients with CLE. CLE with laboratory SLE was defined by 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for SLE score of ≥10 points at baseline with CLE as the sole clinical feature. Of the 149 patients with CLE, 20 had CLE with laboratory SLE. The median follow-up duration was 11.3 years (IQR: 5.1-20.5). Ten patients (7%) had sSLE developed. In survival analysis, the risk of progression to sSLE was higher among CLE with laboratory SLE (hazard ratio = 6.69; 95% CI: 1.93-23.14, P <.001) compared to isolated CLE. In both groups, none of the patients with a risk score ≤ 2 had sSLE developed. Monocentric study with a limited number of patients. CLE with laboratory patients with SLE have a higher risk of progression to sSLE than isolated CLE. [ABSTRACT FROM AUTHOR]

Lupus erythematosus is an autoimmune disease characterised by the formation of various autoantibodies, leading to the involvement of numerous organ systems like the nervous system, renal system, and cutaneous involvement. Cutaneous involvement is the second most common manifestation after musculoskeletal involvement and can range from minor involvement to severe disabling sequelae. The type of skin manifestation can sometimes predict the underlying systemic involvement, as most patients of acute lupus erythematosus have concomitant systemic involvement in contrast to limited chronic cutaneous LE, which has a low incidence of systemic involvement. The cutaneous manifestations have been included in the Systemic Lupus International Collaborating Clinics (SLICC) and American College of Rheumatology criteria for ease in diagnosing lupus erythematosus patients. Herein, we present a review of various cutaneous manifestations seen in association with systemic lupus erythematosus (SLE) patients and their specific management, which can ease the early diagnosis of the patients and triage the patients that will need close follow-up for systemic involvement. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Systemic Lupus Erythematosus is a pleiotropic autoimmune disease with common skin involvement. To date, only one study has investigated tattoos safety in SLE patients. Objective: We performed a single-center study to evaluate the development of local and systemic complications after tattooing in a cohort of systemic lupus erythematosus (SLE) patients. Furthermore, we tried to identify SLE patients who had expressed the will to get a tattoo and why they decided not to. Methods: Consecutive SLE patients were asked to complete a questionnaire about tattoos, including their number, features, and side effects. Open questions were proposed to non-tattooed patients to describe why they did not have tattoos. Results: One hundred ninety-two SLE patients were enrolled [M/F 21/171; median age 41 years (IQR 18)]. Almost 50% of them had at least one tattoo. Seven patients (7.4%) referred adverse reactions to tattoos; interestingly, only one patient experienced a systemic reaction, specifically the occurrence of self-limiting lymphadenopathy. The main reason for not getting a tattoo was the diagnosis of SLE. Conclusions: Our results suggest the safety of tattoos in SLE patients, as demonstrated by a low prevalence of mild adverse events.

Lupus erythematosus (LE) is an autoimmune inflammatory disease with complex etiology. LE may present as a systemic disorder affecting multiple organs or be limited solely to the skin. Cutaneous LE (CLE) manifests with a wide range of skin lesions divided into acute, subacute and chronic subtypes. Despite classic forms of CLE, such as malar rash or discoid LE, little-known variants may occur, for instance hypertrophic LE, chilblain LE and lupus panniculitis. There are also numerous non-specific manifestations including vascular abnormalities, alopecia, pigmentation and nail abnormalities or rheumatoid nodules. Particular cutaneous manifestations correlate with disease activity and thus have great diagnostic value. However, diversity of the clinical picture and resemblance to certain entities delay making an accurate diagnosis The aim of this review is to discuss the variety of cutaneous manifestations and indicate the clinical features of particular CLE types which facilitate differential diagnosis with other dermatoses. Although in diagnostically difficult cases histopathological examination plays a key role in the differential diagnosis of LE, quick and accurate diagnosis ensures adequate therapy implementation and high quality of life for patients. Cooperation between physicians of various specialties is therefore crucial in the management of patients with uncommon and photosensitive skin lesions. [ABSTRACT FROM AUTHOR]

A subtype of cutaneous lupus erythematosus known as lupus erythematosus tumidus (LET) is characterized by sun-exposed areas that typically display urticaria-like papules and plaques. For LET, systemic therapy with antimalarials – particularly hydroxychloroquine (HCQ) – is the first line of treatment. Even though the safety profile of these medications appears to be high, there have been very few reports of side effects in the literature, including hemolytic anemia, retinal toxicity, maculopapular rash, gastrointestinal disturbance, and blue-gray discoloration of the skin or mucous membranes. Here, we report a unique instance of a 46- year-old LET smoker who, following HCQ treatment, developed a generalized myopathy. [ABSTRACT FROM AUTHOR]

Diabetic foot ulcers (DFU) and cutaneous lupus erythematosus (CLE) are both diseases that can seriously affect a patient's quality of life and generate economic pressure in society. Symptomatically, both DLU and CLE exhibit delayed healing and excessive inflammation; however, there is little evidence to support a molecular and cellular connection between these two diseases. In this study, we investigated potential common characteristics between DFU and CLE at the molecular level to provide new insights into skin diseases and regeneration, and identify potential targets for the development of new therapies. The gene expression profiles of DFU and CLE were obtained from the Gene Expression Omnibus (GEO) database and used for analysis. A total of 41 common differentially expressed genes (DEGs), 16 upregulated genes and 25 downregulated genes, were identified between DFU and CLE. GO and KEGG analysis showed that abnormalities in epidermal cells and the activation of inflammatory factors were both involved in the occurrence and development of DFU and CLE. Protein-protein interaction network (PPI) and sub-module analysis identified enrichment in seven common key genes which is KRT16, S100A7, KRT77, OASL, S100A9, EPGN and SAMD9. Based on these seven key genes, we further identified five miRNAs(has-mir-532-5p, has-mir-324-3p,has- mir-106a-5p,has-mir-20a-5p,has-mir-93-5p) and7 transcription factors including CEBPA, CEBPB, GLI1, EP30D, JUN,SP1, NFE2L2 as potential upstream molecules. Functional immune infiltration assays showed that these genes were related to immune cells. The CIBERSORT algorithm and Pearson method were used to determine the correlations between key genes and immune cells, and reverse key gene-immune cell correlations were found between DFU and CLE. Finally, the DGIbd database demonstrated that Paquinimod and Tasquinimod could be used to target S100A9 and Ribavirin could be used to target OASL. Our findings highlight common gene expression characteristics and signaling pathways between DFU and CLE, indicating a close association between these two diseases. This provides guidance for the development of targeted therapies and mutual interactions. [ABSTRACT FROM AUTHOR]

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Background: Polyautoimmunity is defined as having 2 or more autoimmune diseases. Little is known about polyautoimmunity in patients with cutaneous lupus erythematosus (CLE). Objectives: To estimate prevalence and 5-year incidence of non–lupus erythematosus (LE) autoimmune diseases in patients with CLE. Methods: Patients with CLE were identified In the Danish National Patient Registry and each patient was age- and sex-matched with 10 general population controls. Outcome information on non-LE autoimmune diseases was obtained by register-linkage between Danish National Patient Registry and the National Prescription Register. The risk ratio (RR) for prevalent non-LE autoimmune disease at time of CLE diagnosis was calculated in modified Poisson regression; and hazard ratios (HRs) for incident non-LE autoimmune disease were estimated in Cox regression analyses. Results: Overall, 1674 patients with CLE had a higher prevalence of a non-LE autoimmune disease than the comparators (18.5 vs 7.9%; RR 2.4; 95% CI, 2.1 to 2.6). Correspondingly, the cumulative incidence of a non-LE autoimmune disease during 5 years of follow-up was increased for the patients with CLE: HR 3.5 (95% CI, 3.0 to 4.0). Limitations: Risk of detection and misclassification bias, mainly pertaining to the CLE group. Conclusion: Patients with CLE had higher prevalence and 5-year cumulative incidence of a non-LE autoimmune disease than the general population.

Wenting Hu, Si Zhang, Cuihong Lian Department of Dermatology, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Cuihong Lian, Department of Dermatology, Shenzhen Second People’s Hospital, No. 3002 Sungang West Road, Shenzhen, Guangdong, People’s Republic of China, Tel +86 755 83366388, Fax +86 755 83003435, Email liancuihong@email.szu.edu.cnAbstract: Cutaneous lupus erythematosus (CLE) is a group of diseases within the spectrum of lupus that primarily manifests with skin lesions. Discoid lupus erythematosus (DLE) is the most common subtype of CLE. Currently, there is no specific medication available for the treatment of CLE. Here, we reported the efficacy and safety of upadacitinib, a JAK1 selective inhibitor, in treating one DLE patient for 28 weeks. Upadacitinib 15mg QD alone improved DLE lesions significantly, while reduction of the drug to 15mg QOD led to a relapse of the skin lesions. Upadacitinib showed favorable safety in this DLE patient in the 28-week period, except for acne, which was controlled by topical application of benzoyl peroxide gel. In this case, we observed rapid and sustained improvement of DLE lesions using upadacitinib with favorable safety, which provided the opportunity to use upadacitinib as an alternative therapy for DLE.Keywords: cutaneous lupus erythematosus, upadacitinib, JAK inhibitor, discoid lupus erythematosus

Abstract Background Palmoplantar discoid lupus erythematosus (ppDLE) is a rare manifestation of chronic cutaneous lupus erythematosus that can result in painful, hyperkeratotic, and/or erosive lesions on the palms and soles. Despite this penchant to cause significant morbidity, the natural history of ppDLE and its response to conventional treatment approaches remain poorly understood. Objectives To characterize the initial presentation, treatment response, and association with systemic lupus erythematosus (SLE) of ppDLE. Methods We performed an International Classification of Diseases (ICD‐9 and ICD‐10) code and natural‐language query for medical records from Brigham and Women's Hospital and Massachusetts General Hospital to identify all cases of ppDLE based on biopsy and/or expert opinion from January 2000 through October 2022. Demographics, clinical features, and treatment data were analysed. Results Forty‐three patients (median age, 29.5 years [range, 8−70 years]; 36 female [83.7%]) with ppDLE were identified. Mean time from initial clinical presentation of ppDLE symptoms to diagnosis was 14.5 months (n = 34). Of the 43 patients, 74.4% developed coexistent SLE. A mean of 5.9 (standard deviation, 2.7) lines of therapy were required to achieve control of ppDLE, with the majority of patients requiring the initiation of at least two concomitant systemic medications. Conclusions Herein, we present the largest cohort of patients with ppDLE in the literature to date. Despite a high incidence of coexistent SLE, patients experienced lengthy diagnostic delays. Even with appropriate diagnosis, an overwhelming trend towards treatment‐refractory disease was observed.

Immune checkpoint inhibitor (ICI) use has been associated with numerous autoimmune side effects, known as immune related adverse events (irAEs). Cutaneous irAEs are common and affect up to 50% of patients treated with ICIs. There have been an increasing number of cases reported in the literature regarding ICI-induced subacute cutaneous lupus erythematosus (SCLE). ICI-induced SCLE is important to recognize as it can result in a delayed and/or prolonged skin reaction despite treatment discontinuation. We describe a patient with gastro-esophageal adenocarcinoma who developed SCLE following one cycle of nivolumab treatment. A 75-year-old man presented to our clinic with a new photo-distributed rash composed of oval scaly pink papules and plaques involving his chest and arms. Despite treatment with topical corticosteroids, he presented to the emergency department 1 week later with worsening rash. Skin biopsy showed vacuolar interface pattern, along with superficial perivascular lymphocytic infiltrate, consistent with a drug eruption. The clinicopathological presentation was consistent with ICI-induced SCLE. Nivolumab treatment was discontinued due to the severity of the rash. The rash remitted with systemic corticosteroids, high potency topical steroids, and hydroxychloroquine. Unfortunately, the patient developed intraperitoneal metastatic disease, and was enrolled in hospice care. In this paper, we highlight the importance of early identification and treatment of this irAE. A review of the literature, including a discussion on the management of ICI-induced SCLE is also provided.

Diabetic foot ulcers (DFU) and cutaneous lupus erythematosus (CLE) are both diseases that can seriously affect a patient’s quality of life and generate economic pressure in society. Symptomatically, both DLU and CLE exhibit delayed healing and excessive inflammation; however, there is little evidence to support a molecular and cellular connection between these two diseases. In this study, we investigated potential common characteristics between DFU and CLE at the molecular level to provide new insights into skin diseases and regeneration, and identify potential targets for the development of new therapies. The gene expression profiles of DFU and CLE were obtained from the Gene Expression Omnibus (GEO) database and used for analysis. A total of 41 common differentially expressed genes (DEGs), 16 upregulated genes and 25 downregulated genes, were identified between DFU and CLE. GO and KEGG analysis showed that abnormalities in epidermal cells and the activation of inflammatory factors were both involved in the occurrence and development of DFU and CLE. Protein-protein interaction network (PPI) and sub-module analysis identified enrichment in seven common key genes which is KRT16, S100A7, KRT77, OASL, S100A9, EPGN and SAMD9. Based on these seven key genes, we further identified five miRNAs(has-mir-532-5p, has-mir-324-3p,has-mir-106a-5p,has-mir-20a-5p,has-mir-93-5p) and7 transcription factors including CEBPA, CEBPB, GLI1, EP30D, JUN,SP1, NFE2L2 as potential upstream molecules. Functional immune infiltration assays showed that these genes were related to immune cells. The CIBERSORT algorithm and Pearson method were used to determine the correlations between key genes and immune cells, and reverse key gene-immune cell correlations were found between DFU and CLE. Finally, the DGIbd database demonstrated that Paquinimod and Tasquinimod could be used to target S100A9 and Ribavirin could be used to target OASL. Our findings highlight common gene expression characteristics and signaling pathways between DFU and CLE, indicating a close association between these two diseases. This provides guidance for the development of targeted therapies and mutual interactions.

Type 1 interferons (IFNs) play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) and various type I IFNs targeting therapeutic approaches have been developed. Anifrolumab, a monoclonal antibody that binds to the subunit 1 of the type I IFN receptor, has acquired considerable interest and has entered different clinical human trials willing to evaluate its efficacy and safety. This review summarizes the data obtained in phases 1, 2, and 3 clinical trials of anifrolumab for SLE patients. A focus is made on data of clinical efficacy and safety obtained in MUSE, TULIP-1 and TULIP-2 trials. Anifrolumab is a promising therapeutic option for patients with SLE, currently authorized for moderate-to-severe SLE. Extensive real-world use is now going to generate data required to gain experience on the type of patients who benefit the most from the drug, and the exact positioning of anifrolumab in the therapeutic plan. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is complex autoimmune disease with heterogenous manifestations, unpredictable disease course and response to treatment. One of the critical needs in SLE management is the identification of reliable biomarkers that can aid in early diagnosis, accurate monitoring of disease activity, and assessment of treatment response. In the current review, we focus on the commonly affected organs (skin, kidney, and nervous system) in SLE to summarize the emerging biomarkers that show promise in disease diagnosis, monitoring and treatment response assessment. The subtitles within each organ domain were determined based on the most relevant and promising biomarkers for that specific organ damage. Biomarkers have the potential to significantly benefit the management of SLE by aiding in diagnosis, disease activity monitoring, prognosis, and treatment response assessment. However, despite decades of research, none has been validated and implemented for routine clinical use. Novel biomarkers could lead to the development of precision medicine for SLE, guide personalized treatment, and improve patient outcomes. Challenges in biomarker research in SLE include defining clear and clinically relevant questions, accounting for the heterogeneity of SLE, and confirming initial findings in larger, multi-center, multi-ethnic, independent cohorts that reflect real-world clinical scenarios. [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune skin disease which occurs independently and in conjunction with systemic lupus erythematosus. Drug development for CLE is severely lacking. Anandamide (AEA) is a primary endocannabinoid which exhibits immunomodulatory effects through mixed cannabinoid receptor agonism. We evaluated AEA as topical treatment for CLE and assessed benefits of nanoparticle encapsulation (AEA‐NP) on cutaneous drug penetration, delivery and biological activity. Compared to untreated controls, AEA‐NP decreased IL‐6 and MCP‐1 in UVB‐stimulated keratinocytes (p < 0.05) in vitro. In BALB/c mice, AEA‐NP displayed improved cutaneous penetration, extended release and persistence of AEA in the follicular unit extending to the base after 24 h. Utilizing the MRL‐lpr lupus murine model, twice weekly treatment of lesions with topical AEA‐NP for 10 weeks led to decreased clinical and histologic lesion scores compared to unencapsulated AEA and untreated controls (p < 0.05). Prophylactic application of AEA‐NP to commonly involved areas on MRL‐lpr mice similarly resulted in decreased clinical and histologic scores when compared to controls (p < 0.05), and reduced C3 and IBA‐1 in lesional tissue (p < 0.05). The demonstrated clinical and immunomodulatory effects of treatment with AEA support its potential as therapy for CLE. This work also suggests that encapsulation of AEA improves penetration and treatment efficacy. Future studies will be conducted to assess full therapeutic potential. [ABSTRACT FROM AUTHOR]

Objective: The global mortality rates have surged due to the ongoing coronavirus disease 2019 (COVID-19), leading to a worldwide catastrophe. Increasing incidents of patients suffering from cutaneous lupus erythematosus (CLE) exacerbations after either contracting COVID-19 or getting immunized against it, have been observed in recent research. However, the precise intricacies that prompt this unexpected complication are yet to be fully elucidated. This investigation seeks to probe into the molecular events inciting this adverse outcome. Method: Gene expression patterns from the Gene Expression Omnibus (GEO) database, specifically GSE171110 and GSE109248, were extracted. We then discovered common differentially expressed genes (DEGs) in both COVID-19 and CLE. This led to the creation of functional annotations, formation of a protein-protein interaction (PPI) network, and identification of key genes. Furthermore, regulatory networks relating to these shared DEGs and significant genes were constructed. Result: We identified 214 overlapping DEGs in both COVID-19 and CLE datasets. The following functional enrichment analysis of these DEGs highlighted a significant enrichment in pathways related to virus response and infectious disease in both conditions. Next, a PPI network was constructed using bioinformatics tools, resulting in the identification of 5 hub genes. Finally, essential regulatory networks including transcription factor-gene and miRNAgene interactions were determined. Conclusion: Our findings demonstrate shared pathogenesis between COVID-19 and CLE, offering potential insights for future mechanistic investigations. And the identification of common pathways and key genes in these conditions may provide novel avenues for research. [ABSTRACT FROM AUTHOR]

German Shorthaired Pointer (GSHP) dogs with a UNC93B1 gene mutation develop exfoliative cutaneous lupus erythematosus (ECLE) and kidney disease resembling lupus nephritis in humans. The objective of this study was to characterize the kidney disease by light microscopy, immunofluorescence, and electron microscopy in a population of GSHP dogs with ECLE. Medical records were reviewed, and light microscopy of kidneys from 7 GSHP dogs with a previous histologic diagnosis of ECLE was performed. Immunofluorescence of fresh-frozen kidney from 1 dog and transmission electron microscopy of kidney from that dog and 2 additional dogs were performed. Five of 7 dogs had proteinuria diagnosed by urinalysis or urine protein-to-creatinine ratio. Two of 7 dogs were intermittently hypoalbuminemic, and none were azotemic. Histologic findings included early (2 dogs) to late (5 dogs) membranous glomerulonephropathy characterized by mild-to-severe glomerular capillary loop thickening and tubular proteinosis. In all 7 cases, trichrome staining revealed red granular immune deposits on the subepithelial surface of the glomerular basement membrane. Immunofluorescence revealed strong granular labeling for immunoglobulins and complement protein C3. Electron microscopy demonstrated subepithelial electron-dense immune deposits encircled by the remodeled glomerular basement membrane. These findings are diagnostic of immune-complex membranous glomerulonephropathy and are similar to class V lupus in humans. This cohort of GSHP dogs with ECLE developed immune-complex membranous glomerulonephropathy, which we hypothesize is a manifestation of systemic lupus erythematosus. GSHP dogs with ECLE should undergo clinical evaluation of renal function for early identification and treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

IntroductionThe anti-programmed cell death protein 1 (PD-1) antibody cemiplimab has shown promising results in the treatment of unresectable or metastatic squamous cell carcinoma, however, frequently leads to immune-related adverse events limiting therapy efficacy. Although cutaneous side effects are common, only very few cases of cutaneous lupus erythematosus have been reported under anti-PD-1 immunotherapy. So far, no case of cutaneous lupus has been described under treatment with cemiplimab.Case reportFor the first time, we report the case of a patient with advanced squamous cell carcinoma, who developed clinical and histological findings in sun-exposed skin that were consistent with anti-SS-A/Ro antibody-positive subacute cutaneous lupus erythematosus (SCLE) under treatment with cemiplimab. Additionally, laboratory chemical analyses revealed a severe immune-related hepatitis without clinical symptoms. Both, the SCLE and the hepatitis, resolved after the administration of topical and systemic steroids and the discontinuation of anti-PD-1 therapy.ConclusionTreatment with cemiplimab can be associated with the appearance of cutaneous lupus erythematosus in sun-exposed areas. Application of topical and systemic glucocorticoids can lead to a rapid resolution of the skin eruptions. Moreover, our case illustrates the possibility of simultaneously occurring severe immune-related adverse events. This highlights the importance of additional diagnostics to avoid overlooking additional immune-related adverse events.

Vaccine development for COVID-19 has progressed expeditiously. To date, the Food and Drug Administration (FDA) has authorized the Moderna/mRNA-1273, Pfizer-BioNTech (BNT162b2), and Johnson & Johnson’s Janssen (JNJ-78436735) vaccines for use in the United States. Immediate side effects have included myalgia fatigue, chills, fever, and headache. We report an elderly patient with a history of lung cancer and no prior history of autoimmune disease who developed cutaneous lupus erythematosus two ½ months after the second dose of the Pfizer-BioNTech COVID-19 vaccine.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with varied dermatological manifestations that are almost universal. Overall, lupus disease has a major effect on the quality of life in these patients. We assessed the extent of cutaneous disease in early lupus and correlated it with the SLE quality-of-life (SLEQoL) index and disease activity measures. Patients diagnosed as SLE with the skin involved were recruited at the first presentation and were assessed for cutaneous and systemic disease activity using the cutaneous lupus erythematosus disease area and severity index (CLASI) and the Mexican-SLE disease activity index (Mex-SLEDAI), respectively. Quality of life was assessed with the SLEQoL tool while systemic damage was captured by the SLICC damage index. Fifty-two patients with SLE who had cutaneous involvement were enrolled (40, 76.9% females) with a median disease duration of 1 month (1–3.7). The median age was 27.5 years (IQR: 20–41). Median Mex-SLEDAI and SLICC damage index were 8(IQR: 4.5–11) and 0 (0–1), respectively. The median CLASI activity and damage scores were 3 (1–5) and 1 (0–1), respectively. Overall, there was no correlation between SLEQoL with CLASI or CLASI damage. Only the self-image domain of SLEQoL correlated with total CLASI (ρ = 0.32; p = 0.01) and CLASI-D (ρ = 0.35; p = 0.02). There was a weak correlation of CLASI with the Mexican-SLEDAI score (ρ = 0.30; p = 0.03) but not with the SLICC damage index. In this cohort of early lupus, cutaneous disease activity in lupus had a weak correlation with systemic disease. Cutaneous features did not appear to influence the quality of life except in the self-image domain. [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease with various clinical forms, including the subtypes of discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). The altered function of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis in CLE pathogenesis has been suggested. Here, the soluble forms of PD-1 (sPD-1) and PD-L1 (sPD-L1) were explored in untreated DLE and SCLE. Levels of sPD-1 and sPD-L1 were determined by enzyme-linked immunosorbent assay in serums of 21 DLE, 18 SCLE, 13 systemic lupus erythematosus (SLE) patients and 20 healthy controls (HCs). Differences between patient groups and HCs, and the association between clinical activity of skin symptoms and sPD-1/sPD-L1 levels were analyzed with Mann–Whitney U-test and Spearmann's correlation. Regarding sPD-1 levels, no statistically significant differences were found between DLE and SCLE groups, nor compared to HCs. As for sPD-L1, a significantly lower level was found in the DLE group compared to the SCLE and HC groups (p = 0.027 and p = 0.009, respectively). In SLE, significantly higher sPD-1 was found compared to HCs (p = 0.002). No association between skin symptom activity and sPD-1/sPD-L1 levels was found in CLE. Alterations of the inhibitory effect of sPD-L1 on T-cell activity might elucidate the differences between DLE and SCLE. [ABSTRACT FROM AUTHOR]

Prinpat Pinyowiwat, Suthinee Rutnin, Kumutnart Chanprapaph Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Kumutnart Chanprapaph, Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama IV Road, Ratchatewi, Bangkok, 10400, Thailand, Tel +662-201-1141, Fax +662-201-1211, Email kumutnartp@hotmail.comAbstract: Sclerodermic or scleroderma-like lupus erythematosus panniculitis (SLEP) shares both clinical and histopathological features between lupus panniculitis and localized scleroderma. It is exceedingly rare. We herein report a case of SLEP manifested with a solitary, firm-to-hard, erythematous plaque in an Asian woman. This patient responded well to intralesional corticosteroid and antimalarials. We have reviewed the pathogenesis of fibrosis in patients with chronic cutaneous lupus erythematosus as well as documented cases of SLEP in the literature.Keywords: cutaneous lupus erythematosus, scleroderma-like lupus erythematosus panniculitis, sclerodermic lupus panniculitis, localized scleroderma, lupus profundus, overlap syndrome

Cutaneous disease is one of the most frequent manifestations of systemic lupus erythematosus (SLE), being classified as LE-specific and LE-nonspecific. LE-specific skin lesions are divided into acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). The association with systemic involvement varies between each clinical subtype, with non-specific lesions being more frequent associated with active SLE than cutaneous specific lesions. The treatment consists of topical agents (glucocorticoids, topical calcineurin inhibitors) as well as systemic therapies (glucocorticoids, hydroxychloroquine, quinacrine, methotrexate, retinoids, dapsone, mycophenolate mofetil or even biologics). In the presence of strictly cutaneous involvement, periodic patient follow-up and monitoring for the progression to systemic disease remains an important mission for the dermatologist and the rheumatologist.