Cutaneous Lupus Erythematosus Lesions Research Articles

A crack in the armor: Wolf isotopic response manifesting as cutaneous lupus.

Wolf isotopic response represents the development of skin lesions of one particular morphology occurring at the same site as another morphologically distinct and unrelated skin lesion. Cutaneous lupus erythematosus (CLE) is an autoimmune connective tissue disorder encompassing a wide range of phenotypes that may be associated with systemic involvement. Although CLE is a well-described entity with a broad spectrum, the occurrence of lesions manifesting as an isotopic response is rare. We present a patient with systemic lupus erythematosus who developed CLE in a dermatomal distribution following herpes zoster. When CLE lesions present in a dermatomal distribution, these cases may be difficult to distinguish from recurrent herpes zoster infection in an immunosuppressed patient. Therefore, they pose a diagnostic challenge and require balancing antiviral therapy with immunosuppression to sufficiently maintain adequate control of the autoimmune disease while addressing possible infections. To avoid treatment delay, clinicians should have elevated suspicion for an isotopic response when disparate lesions erupt in areas previously affected by herpes zoster or in cases of persistent eruptions at sites of prior herpes zoster. We discuss this case within the context of Wolf isotopic response and review the literature for similar cases.

31341 BIIB059 reduces disease activity over 16 weeks in active cutaneous lupus erythematosus (CLE): Results from part B of phase 2 LILAC study

Part B of the phase 2 LILAC (NCT02847598) study demonstrated at week 16 the efficacy of BIIB059 50, 150, and 450 mg versus placebo (CLASI-50 response [450 mg; P = .024]) subcutaneously administered every 4 weeks (with 1 additional dose at week 2) in CLE participants with active SCLE and/or chronic CLE lesions. In these exploratory analyses, we evaluated the proportion of participants with a 20% (CLASI-20 response) or 70% (CLASI-70 response) improvement in CLASI-A score over 16 weeks. Among 132 participants, 26, 25, 48, and 33 received BIIB059 50, 150, and 450 mg and placebo, respectively. For BIIB059 50, 150, and 450 mg versus placebo, the proportion of participants who achieved CLASI-20 response was 15.4%, 28.0%, and 33.3% versus 15.2% at week 2; 42.3%, 64.0%, and 56.3% versus 30.3% at week 4; 50.0%, 76.0%, and 52.1% versus 42.4% at week 8; 50.0%, 80.0%, and 56.3% versus 42.4% at week 12; and 46.2%, 72.0%, and 72.1% versus 43.8% at week 16. For the same treatment groups, the proportion of participants who achieved CLASI-70 response was 3.8%, 0, and 0 versus 0 at week 2; 3.8%, 12.0%, and 10.4% versus 0 at week 4; 19.2%, 24.0%, and 18.8% versus 6.1% at week 8; 19.2%, 24.0%, and 14.6% versus 6.1% at week 12; and 15.4%, 32.0%, and 27.9% versus 9.4% at week 16. A greater proportion of CLE participants treated with BIIB059 versus placebo had improvement in disease activity over time using different thresholds for CLASI-A response.

Downregulation of miR-885-5p Promotes NF-κB Pathway Activation and Immune Recruitment in Cutaneous Lupus Erythematosus

Cutaneous lupus erythematosus (CLE) has a specific microRNA expression profile. MiR-885-5p has been found to be downregulated in the epidermis of CLE lesions; however, its biological role in the disease has not been studied. In this study, we show that miR-885-5p is markedly reduced in CLE keratinocytes (KCs) with IFN-α and UVB being strong miR-885-5p regulators invitro. Microarray expression profiling of anti‒miR-885-5p‒transfected KCs identified PSMB5 as a direct target. Specific inhibition of miR-885-5p increased epidermal proliferation by modulating keratin 16 gene K16, BIRC5, TP63, and CDK4 proliferative genes and promoted NF-κB signaling pathway in human primary KCs by increasing IκBα degradation. Silencing PSMB5 rescued the effect of miR-885-5p inhibition, indicating that miR-885-5p regulates proliferation and NF-κB activation by targeting PSMB5 in KCs. In addition, inhibition of miR-885-5p increased the ability of KCs to attract leukocytes in a PSMB5-independent manner. We identified TRAF1 as another direct target, and its silencing reduced leukocyte migration. Collectively, our findings suggest that UVB and IFN-ɑ downregulate miR-885-5p in CLE KCs, leading to epidermal inflammation by NF-κB activity enhancement and proliferation through PSMB5 and immune recruitment through TRAF1. Our data indicate that miR-885-5p is a potential therapeutic target in 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.

Prevalence and factors associated with long-term remission in cutaneous lupus: A longitudinal cohort study of 141 cases

Little is known about the prevalence and factors associated with long-term remission in cutaneous lupus erythematosus (CLE). To assess the prevalence, the factors associated with remission, and the long-term remission with and without treatment during CLE. Longitudinal cohort study including biopsy-proven patients with CLE seen between November 1, 2019 and April 30, 2021, with at least 6months of follow-up after diagnosis. Demographic data, CLE subtypes, remission status, and treatments were recorded. Remission was defined by a Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score of 0. Long-term remission was defined by remission >3years. Among 141 patients included (81% of women), 93 (66%) were in remission at last follow-up with a median duration since diagnosis of 11.4years (interquartile range, 4.2-24.7). Long-term remission was observed in 22 (19%) of 114 patients with at least 3years of follow-up, including 5 (4.4%) with no systemic treatment. Active smoking (odds ratio, 0.22 [95%CI: 0.05-0.97]; P=.04) and discoid CLE lesions (odds ratio, 0.14 [95%CI, 0.04-0.48]; P=.004) were associated with a lower risk of long-term remission. Partial retrospective data collection and tertiary center population. Long-term remission is rare in CLE and negatively associated with active smoking and discoid CLE.

Skin CD4+ Trm cells distinguish acute cutaneous lupus erythematosus from localized discoid lupus erythematosus/subacute cutaneous lupus erythematosus and other skin diseases

BackgroundAlthough the contribution of aberrant CD4+ T cell signaling to systemic lupus erythematosus (SLE) is well established, its role in cutaneous lupus erythematosus (CLE) skin is largely unknown. Because the rate of systemic manifestations varies in each subtype, resident memory CD4+ T cells in lesions that are responsible for only skin-associated tissue responses may vary in each subtype. However, the role of CD4+ tissue-resident memory T (CD4+ Trm) cells in each CLE subtype remains unclear. ObjectivesTo analyze and compare CD4+ Trm cells and absent in melanoma 2 (AIM2) identified by smart RNA sequencing (Smart-seq) in CD4+ Trm cells from patients with acute CLE (ACLE), subacute CLE (SCLE), and localized discoid lupus erythematosus (localized DLE) lesions. MethodsWe performed Smart-seq to investigate differences in dermal CD4+ Trm cells between patients with ACLE and normal controls (NCs). Multicolor immunohistochemistry was utilized to measure the levels of AIM2 in CD4+ Trm cells present in the skin of 134 clinical patients, which included patients with localized DLE (n = 19), ACLE (n = 19), SCLE (n = 16), psoriasis (n = 12), rosacea (n = 17), lichen planus (n = 18), and annular granuloma (n = 15), as well as NCs (n = 18). ResultsThe Smart-seq data showed higher AIM2 expression in skin CD4+ Trm cells from ACLE lesions than NCs (fold change >10, adjusted P < 0.05). AIM2 expression in CD4+ Trm cells did not vary according to age or sex. AIM2 expression in CD4+ Trm cells was significantly lower in patients with ACLE (6.38 ± 5.22) than localized DLE (179.41 ± 160.98, P < 0.0001) and SCLE (63.43 ± 62.27, P < 0.05). In an overall comparison of ACLE with localized DLE and SCLE, the receiver operating characteristic curve for AIM2 expression in CD4+ Trm cells had a sensitivity of 100.00% and a specificity of 82.86% at a cutoff value of 18.26. In a comparison of ACLE with localized DLE, the sensitivity was 89.47%, and the specificity was 100.00% at a cutoff value of 12.26. In a comparison of ACLE with SCLE, the sensitivity was 100.00%, and the specificity was 75.00% at a cutoff value of 18.26. ConclusionsThe number of CD4+ Trm cells is increased in lesions of SCLE and localized DLE compared to ACLE, suggesting that CD4+ Trm cells may have a more crucial role in persistent lesions of SCLE and localized DLE. In addition, AIM2 expression in CD4+ Trm cells discriminates patients with ACLE from those with localized DLE and SCLE.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

Immunogenetics of Lupus Erythematosus.

Lupus erythematosus (LE) is a heterogeneous disease with a wide range of manifestations ranging from localized lesions in cutaneous lupus erythematosus (CLE) to severe disseminated disease in systemic lupus erythematosus (SLE).Lupus results from a complex interaction between genetic and epigenetic backgrounds and environmental triggers that cause loss of tolerance to self-antigens and the formation of autoantibodies. Genetic susceptibility plays a key role in the pathogenesis of lupus erythematosus. In most cases, multiple common alleles with modest effect sizes are combined to result in the polygenic inheritance of the disease but monogenic variants of lupus have also been described. Genes from the innate and adaptive immune system along with genes involved in apoptosis and immunoglobulin clearance have been linked to SLE. This chapter aims to explore the functions of these genes and their contribution to the pathogenesis of the disease.

27475 Efficacy of the BIIB059 monoclonal antibody against BDCA2 in active cutaneous lupus erythematosus (CLE): Subgroup analyses of participants with or without systemic LE (SLE) and with different levels of disease activity

CLE is an autoimmune disease occurring with or without systemic manifestations that significantly impairs health-related QoL. In the phase 2 LILAC (NCT02847598) study (part B), efficacy of BIIB059 50mg, 150mg, and 450mg vs placebo SC Q4W was demonstrated in participants with CLASI-A scores ≥8 and ≥1 subacute and/or chronic CLE lesions. In the subgroup analyses presented here, percentage changes from baseline in CLASI-A scores were analyzed in CLE participants with vs without concomitant SLE and in those with baseline CLASI-A<10 vs ≥10. The overall modified intent-to-treat population consisted of n = 33 (placebo), n = 26 (BIIB059 50mg), n = 25 (BIIB059 150mg), and n = 48 (BIIB059 450mg). The least squares (LS) mean differences from placebo (95%CI) in percentage change in CLASI-A at week 16 for participants with SLE were -31.01 (-61.61,-0.41; n = 11; BIIB059 50mg), -34.93 (-63.86,-6.00; n = 12; BIIB059 150mg), and -19.04 (-44.44,6.35; n = 20; BIIB059 450mg). For participants without SLE, they were -21.08 (-47.00,4.84; n = 15; BIIB059 50mg), -33.58 (-60.36,-6.79; n = 13; BIIB059 150mg), and -36.52 (-59.09,-13.95; n = 28; BIIB059 450mg). The LS mean differences from placebo (95%CI) in percentage change in CLASI-A at week 16 for participants with CLASI-A<10 were 25.38 (58.82,8.06; n = 6; BIIB059 50mg), 59.37 (97.19,21.55; n = 4; BIIB059 150mg), and 28.64 (59.67,2.39; n = 8; BIIB059 450mg). For CLASI-A≥10, they were 23.48 (47.00,0.05; n = 20; BIIB059 50mg), 28.08 (50.72,5.44; n = 21; BIIB059 150mg), and 26.21 (45.91,6.51; n = 40; BIIB059 450mg). The incidence of AEs in the overall study population was similar between the placebo and BIIB059 groups. Although the subgroup analyses are limited by small sample sizes and are not powered for statistical testing, BIIB059 efficacy was observed regardless of SLE presence or disease severity, consistent with the primary analysis in part B of the LILAC study.

Guideline for the diagnosis, treatment and long-term management of cutaneous lupus erythematosus

Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.

S2k guideline: Diagnosis and management of cutaneous lupus erythematosus - Part1: Classification, diagnosis, prevention, activity scores.

S2k guideline: Diagnosis and management of cutaneous lupus erythematosus - Part1: Classification, diagnosis, prevention, activity scores.

Senescent Progenitor Cells in the Skin of Patients with Cutaneous Lupus Erythematosus

Senescent Progenitor Cells in the Skin of Patients with Cutaneous Lupus Erythematosus

Treatments for disease damage in cutaneous lupus erythematosus: A narrative review.

Cutaneous lupus erythematosus (CLE) is an autoimmune photosensitive disorder that affects the skin. CLE lesions can have signs of skin damage including dyspigmentation, scarring, atrophy and/or alopecia. Disease damage secondary to CLE can be cosmetically disfiguring and causes patients significant distress. While many current treatments for CLE focus primarily on reducing inflammation, there are few options for managing disease damage. Providers currently lack strong guidance on managing CLE damage due to the paucity of literature on this topic. Because of this knowledge gap, we aim to provide an overview of what is currently known about the pathogenesis and management of signs of disease damage in CLE. In this narrative review, Pubmed, Ovid Medline, and Google scholar were searched for relevant articles assessing pathogenesis and treatment of disease damage. Therapeutic options for CLE damage, including hyperpigmentation (laser and camouflage), hypopigmentation (melanocyte grafting and camouflage), scarring (laser, dermabrasion, and camouflage), atrophy (filler, fat transplantation, and flap procedures), and scarring alopecia (hair transplantation and camouflage) were identified. We found that investigations of therapeutics for CLE disease damage primarily consist of case reports and small case series. Reported adverse events due to treatment for CLE disease damage range from temporary erythema and discomfort to disease reactivation and pigmentary defects. There are various treatments for disease damage for each sign of disease damage. However, more robust investigations are needed to assess disease pathogenesis and improve treatments of disease damage due to CLE.

Expression pattern of tissue-resident memory T cells in cutaneous lupus erythematosus.

Tissue resident memory T cells (TRMs) persist long-term in peripheral tissues without recirculation, triggering an immediate protective inflammatory state upon the re-recognition of the antigen. Despite evidence incriminating the dysregulation of TRMs in autoimmune diseases, few studies have examined their expression in cutaneous lupus erythematosus (CLE). We aimed to examine whether there are differences among TRM populations in CLE depending on different clinical conditions, such as the CLE subtype or association with systemic lupus erythematosus, and to determine the effect of type I interferon (IFN) on the development of TRMs in CLE. CLE disease activity was evaluated using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. The expression of the TRM markers CD69 and CD103 in CLE lesions was evaluated by immunofluorescence. Flow cytometry was performed on peripheral blood mononuclear cells after IFNα treatment. The number of TRMs expressing either CD69 or CD103 was significantly higher in CLE lesions than in control skin; however, it was not significantly different between discoid lupus erythematosus and subacute CLE, or dependent on the presence of concomitant systemic lupus. Lesional severity was not correlated with an increase in TRMs in CLE. IFNα treatment induced a conspicuous increase in CD69 expression in skin-homing T cells, more profoundly in CD4+ T cells than in CD8+ T cells. Skin TRMs, either CD69 or CD103-positive cells, showed increased levels in the lesional skin of CLE, and IFNα increased the expression of CD69 in T cells.

Proteome study of cutaneous lupus erythematosus (CLE) and dermatomyositis skin lesions reveals IL-16 is differentially upregulated in CLE

BackgroundThe objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM).MethodsSkin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Protein pathway analysis was performed by the string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC).ResultsProteome investigation identified abundant expression of interferon-regulated proteins (IRP) as a common feature of CLE and DM. Interleukin (IL)-16 was the only abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, an enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16- and caspase-3-positive cells was identified in CLE lesions in comparison with DM, PC, and HC. Proteomic results indicate more abundant complement deposition in CLE skin lesions.ConclusionsUsing unbiased mass spectrometry investigation of CLE and DM inflammatory infiltrates, we confirmed that high IRP expression is a common feature of both CLE and DM, while IL-16 is the only differentially expressed cytokine in CLE. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. IL-16 could be of interest as a future therapeutic target for CLE.

The Koebner phenomenon on tattoos and piercings in a patient with cutaneous lupus: a case report and review of the literature

The Koebner phenomenon is associated with cutaneous lupus erythematosus (CLE). A 20-year-old woman with a 10-year history of systemic lupus, treated with hydroxychloroquine and methotrexate, presented with features of chronic discoid lupus erythematosus (DLE) on the scalp, at the site of ear piercings, and on the temporal bone at the site of trauma from her jewelry. She also had subacute CLE (SCLE) lesions on old black tattoos. Histology and direct immunofluorescence confirmed CLE. We reviewed 13 cases of Koebner phenomenon on tattoos in patients with CLE (seven men, median age: 31.5 years) and none after piercings. Lesions developed within 1 week to 16 years after tattooing. Lesions may be isolated, precede, or be associated with other CLE lesions. They can appear secondarily on the tattoo. There is no specific color affinity, but cases have shifted from red to black, possibly when mercury was withdrawn from red inks. CLE on tattoos is a rare phenomenon that more often presents with DLE features than SCLE. Patients should be warned of the potential risk of developing lesions on tattoos. Immunosuppressive treatment needs to be taken into account if a patient wishes to get a tattoo. However, tattooing is not associated with severe complications.

Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study.

The immunoregulator spleen tyrosine kinase (SYK) is upregulated in cutaneous lupus erythematosus (CLE). This double‐blind, multicentre, Phase Ib study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical efficacy of the selective SYK inhibitor GSK2646264 in active CLE lesions. Two lesions from each participant (n = 11) were each randomized to topical application of 1% (w/w) GSK2646264 or placebo for 28 days; all participants received GSK2646264 and placebo. The primary endpoint was safety and tolerability of GSK2646264, assessed by adverse event incidence and a skin tolerability test. Secondary endpoints included change from baseline in clinical activity and mRNA expression of interferon‐related genes in skin biopsies. Levels of several immune cell markers were evaluated over time. Eight (73%) participants experienced ≥ 1 adverse event (all mild in intensity), and maximal dermal response was similar for GSK2646264 and placebo. The expression of several interferon‐related genes, including CXCL10 and OAS1, showed modest decreases from baseline after 28 days of treatment with GSK2646264 compared with placebo. Similar findings were observed for CD3 + T cell and CD11c + dendritic cell levels; however, overall clinical activity remained unchanged with GSK2646264 vs. placebo. Further studies are warranted to assess SYK inhibitors as potential treatment for CLE.

The pathogenesis of cutaneous lupus erythematosus: The aberrant distribution and function of different cell types in skin lesions

Cutaneous lupus erythematosus (CLE) is an autoimmune disease with a broad range of cutaneous manifestations. In skin lesions of CLE, keratinocytes primarily undergo apoptosis. Interferon-κ(IFN-κ) is belonged to type I interferons (type I IFNs) and is selectively produced by keratinocytes. Recently, keratinocytes selectively produced IFN-κ is identified to be a key to trigger type I interferon responses in CLE. Other immune cells such as plasmacytoid dendritic cells (pDCs) are identified to be relevant origin of type I interferons (type I IFNs) which are central to the development of CLE lesions and responsible for mediating Th1 cell activity. Other types of cells such as neutrophils, B cells and Th17 cells also are involved in the development of this disease. The close interaction of those cells composes a comprehensive and complicated network in CLE. In this review, we discussed the aberrant distribution and function of different cells types involved in this disease and will offer a new direction for research and therapy in the near future.

IL18-containing 5-gene signature distinguishes histologically identical dermatomyositis and lupus erythematosus skin lesions.

Skin lesions in dermatomyositis (DM) are common, are frequently refractory, and have prognostic significance. Histologically, DM lesions appear similar to cutaneous lupus erythematosus (CLE) lesions and frequently cannot be differentiated. We thus compared the transcriptional profile of DM biopsies with CLE lesions to identify unique features. Type I IFN signaling, including IFN-κ upregulation, was a common pathway in both DM and CLE; however, CLE also exhibited other inflammatory pathways. Notably, DM lesions could be distinguished from CLE by a 5-gene biomarker panel that included IL18 upregulation. Using single-cell RNA-sequencing, we further identified keratinocytes as the main source of increased IL-18 in DM skin. This study identifies a potentially novel molecular signature, with significant clinical implications for differentiating DM from CLE lesions, and highlights the potential role for IL-18 in the pathophysiology of DM skin disease.

Cutaneous Lupus Erythematosus: Disease Area and Severity Index reliability in clinical evaluation and assessment of cutaneous lupus erythematosus lesions in pediatric cases

Background: Children having systemic lupus erythematosus clinically reflect a management and diagnostic challenge. Cutaneous lupus erythematosus reflects the dermatological signs of SLE categorized into LE-specific and LE-nonspecific features. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Physician Global Assessment (PGA) are clinical tools categorizing the dermatological disease severity in cases having cutaneous lupus disease Aim of study: Assessment of CLASI scoring reliability and usefulness in pediatric cutaneous lupus. Methodology: A clinical research trial conducted on 100 research study subjects with pediatric cutaneous lupus erythematosus. Cases had an age range of 6–18 years. All research study subjects were assessed using both the CLASI and skin Physician’s Global Assessment clinical tools. Results: CLASI activity had excellent inter-rater and intra-rater reliability scores among dermatologists and rheumatologists (ICC = 0.965, 0.993, 0.924, 0.975 consecutively), CLASI damage had good interrater and intra rater scores among dermatologists (ICC = 0.810, 0.893 consecutively) on the other hand among rheumatologists it had poor interrater score (ICC =0.397) and good intra rater score (ICC =0.786). PGA activity had good inter rater reliability (ICC=0.830) and excellent intra rater variability (0.912) among dermatologists and among rheumatologists had fair inter rater and intra rater reliability (ICC=0.754, 0.784 consecutively) PGA damage had moderate inter rater reliability (ICC=0.593, 0.684) and fair intra rater reliability (ICC=0.783, 0.756) among dermatologists and rheumatologists consecutively.