Subtypes Of Lupus Erythematosus Research Articles

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

The Possible Clinical Significance of a Decreased Serum Level of Soluble PD-L1 in Discoid Lupus Erythematosus, but Not in Subacute Cutaneous Lupus Erythematosus-A Pilot Study.

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.

Characterization of B cells in lupus erythematosus skin biopsies in the context of different immune cell infiltration patterns.

Cutaneous lesions in lupus erythematosus (LE) subtypes are heterogenous. In line with the heterogeneity of the clinical presentation, the underlying lesional inflammation in LE skin samples is defined by different immune cell infiltrates. Pathophysiologically, lesional inflammation is driven by autoreactive cytotoxic T cells, targeting keratinocytes; plasmacytoid dendritic cells (pDCs), producing large amounts of interferon (IFN); and B cells, whose function in cutaneous LE is still unclear. This study aims to (a) classify inflammatory patterns with regard to the dominating cell type or cytokine expression and (b) investigating the specific role of B cells in LE skin lesions. Therefore, the immunohistological expression of inflammatory surrogates (CD20, CD123, MXA) in skin samples of n = 119 LE (subtypes: subacute cutaneous LE, chronic discoid LE, chilblain LE, LE tumidus, other LE) and n = 17 patients with inflammatory skin diseases (atopic dermatitis, psoriasis) were assessed. Samples were classified with regard to inflammatory groups. In addition multiplex-immunohistochemical analyses of n = 17 LE skin samples focusing on lesional B cells were conducted. In this study, we show that cutaneous lesions present with eight different inflammatory groups dominated by B cells, pDCs, a strong IFN expression, or overlapping patterns. Altogether, LE subtypes show heterogenous infiltration regardless of LE subtype, certain subtypes display a preference for infiltration groups. Furthermore, lesional B cells either form diffuse infiltrates or pseudofollicular structures, wherein they show antigen-presenting and T cell-activating properties. Altogether, in the light of emerging targeted therapeutic options, we suggest histological assessment in regard to B-cell or pDC preponderance to allow tailored treatment decisions.

Dynamics of Methylation of CpG Sites Associated With Systemic Lupus Erythematosus Subtypes in a Longitudinal Cohort.

Findings from cross-sectional studies have revealed associations between DNA methylation and systemic lupus erythematosus (SLE) outcomes. This study was undertaken to investigate the dynamics of DNA methylation by examining participants from an SLE longitudinal cohort using samples collected at 2 time points. A total of 101 participants from the California Lupus Epidemiology Study were included in our analysis. DNA was extracted from blood samples collected at the time of enrolment in the cohort and samples collected after 2 years and was analyzed using Illumina EPIC BeadChip kit. Paired t-tests were used to identify genome-wide changes which included 256 CpG sites previously found to be associated with SLE subtypes. Linear mixed models were developed to understand the relationship between DNA methylation and disease activity, medication use, and sample cell-type proportions, adjusted for age, sex, and genetic principal components. The majority of CpGs that were previously determined to be associated with SLE subtypes remained stable over 2 years (185 CpGs [72.3%]; t-test false discovery rate >0.05). Compared to background genome-wide methylation, there was an enrichment of SLE subtype-associated CpGs that changed over time (27.7% versus 0.34%). Changes in cell-type proportions were associated with changes at 67 CpGs (P < 2.70 × 10-5 ), and 15 CpGs had at least 1 significant association with immunosuppressant use. In this longitudinal SLE cohort, we identified a subset of SLE subtype-associated CpGs that remained stable over time and may be useful as biomarkers of disease subtypes. Another subset of SLE subtype-associated CpGs changed at a higher proportion compared to the genome-wide methylome. Additional studies are needed to understand the etiology and impact of these changes on methylation of SLE-associated CpGs.

Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus.

This study explored the correlation between peripheral blood CD3＋, CD3＋/CD4＋, CD3+/CD8+, CD4＋/CD8＋, CD3−/CD16+ CD56+, and CD3−CD19+ and disease activity of different subtypes of systemic lupus erythematosus (SLE). The percentages of CD3+, CD3+/CD4+, CD3+/CD8+, CD4+/CD8+, CD3−/CD16+ CD56+, and CD3−CD19+ in the peripheral blood of patients (n = 80) classified into lupus nephritis, blood involvement, and joint involvement and SLE in different active stages were detected by flow cytometry. Their correlations with baseline clinical experimental indicators of SLE patients’ SLE disease activity index score (SLEDAI) and complement C3 were analyzed. The results showed that CD3+, CD3+/CD4+, and CD3+/CD8+ at baseline level were negatively correlated with SLEDAI scores. These were positively correlated with C3. In conclusion, T-lymphocyte subpopulations are closely related to SLE activity and can be used as reference indicators to evaluate the SLE activity.

Scoring personalized molecular portraits identify Systemic Lupus Erythematosus subtypes and predict individualized drug responses, symptomatology and disease progression.

ObjectivesSystemic Lupus Erythematosus is a complex autoimmune disease that leads to significant worsening of quality of life and mortality. Flares appear unpredictably during the disease course and therapies used are often only partially effective. These challenges are mainly due to the molecular heterogeneity of the disease, and in this context, personalized medicine-based approaches offer major promise. With this work we intended to advance in that direction by developing MyPROSLE, an omic-based analytical workflow for measuring the molecular portrait of individual patients to support clinicians in their therapeutic decisions.MethodsImmunological gene-modules were used to represent the transcriptome of the patients. A dysregulation score for each gene-module was calculated at the patient level based on averaged z-scores. Almost 6100 Lupus and 750 healthy samples were used to analyze the association among dysregulation scores, clinical manifestations, prognosis, flare and remission events and response to Tabalumab. Machine learning-based classification models were built to predict around 100 different clinical parameters based on personalized dysregulation scores.ResultsMyPROSLE allows to molecularly summarize patients in 206 gene-modules, clustered into nine main lupus signatures. The combination of these modules revealed highly differentiated pathological mechanisms. We found that the dysregulation of certain gene-modules is strongly associated with specific clinical manifestations, the occurrence of relapses or the presence of long-term remission and drug response. Therefore, MyPROSLE may be used to accurately predict these clinical outcomes.ConclusionsMyPROSLE (https://myprosle.genyo.es) allows molecular characterization of individual Lupus patients and it extracts key molecular information to support more precise therapeutic decisions.

Clusters of clinical and immunologic features in patients with bullous systemic lupus erythematosus: experience from a single-center cohort study in China

BackgroundBullous systemic lupus erythematosus (BSLE) is a rare subtype of systemic lupus erythematosus (SLE) that is clinically characterized by subepidermal tense vesicles or bullae. We aimed to investigate the clinical and laboratory features of patients with BSLE.MethodsWe retrospectively reviewed all patients who fulfilled the diagnostic criteria for BSLE in our institution from 2015 to 2021. Cutaneous lesions, systemic manifestations, treatment options, and outcomes were evaluated. For each case of BSLE, four controls were randomly selected from patients with single SLE. Major clinical and laboratory characteristics were compared between the two groups.ResultsAmong 4221 patients with SLE, 12 developed BSLE. Vesiculobullous lesions were the first sign in five of the BSLE patients (5/12, 41.7%) and appeared after SLE diagnosis in the remaining seven patients (7/12, 58.3%), with a median duration from SLE onset of 36 months (4–115 months). The most common BSLE-affected sites were the head and neck (10/12, 83.3%), extremities (9/12, 75.0%), trunk (7/12, 58.3%), and mucosae (6/12, 50.0%). All patients with BSLE had extra-cutaneous involvement. The SLE disease activity index score exceeded 5 in 10/12 (83.3%) patients, which indicated high disease activity. Patients in the BSLE group had significantly higher incidences of proteinuria (83.3% vs. 47.9%, P = 0.027), hematuria (75% vs. 31.3%, P = 0.006), hemolytic anemia (33.3% vs. 0%, P = 0.000), and leukopenia (66.7% vs. 25.0%, P = 0.006) than those in the control group. The use of systemic corticosteroids, immunosuppressants, dapsone, and skin care was effective in controlling disease.ConclusionsVesiculobullous lesions may be the first manifestation and indicate a high disease activity in patients with BSLE. Early diagnosis using clinical, histopathological, and immunological evaluations can lead to appropriate treatment of this progressive disease and improve prognosis.

Identification of biomarkers related to neutrophils and two molecular subtypes of systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE), an autoimmune disease with complex pathogenesis, poses a considerable threat to women’s health. Increasing evidence indicates that neutrophils play an important role in the development and progression of lupus.MethodsWeighted correlation network analysis and single-sample gene set enrichment analysis (GSEA) were used to analyse SLE expression data from a comprehensive gene expression database and identify modules associated with neutrophils. Thereafter, the biomarkers most closely related to neutrophils were identified. We reclassified SLE into two molecular subtypes based on the aforementioned biomarkers and evaluated cell infiltration, molecular mechanisms, and signature pathways in each subtype.ResultsThe results showed significant differences in immunological characteristics between the two molecular subtypes of SLE. Hub genes were significantly upregulated in the NEUT-H subtype, and they may be associated with lupus activity. The GSEA revealed associations between our biomarkers and key metabolic pathways.ConclusionsOur study provides not only a classification for patients with SLE but also new cell and gene targets for immunotherapy, as well as a new experimental paradigm to explore immunotherapy for other autoimmune diseases.

Systemic lupus erythematosus with trisomy X: a case report and review of the literature

BackgroundThe cause of systemic lupus erythematosus is not completely clear so far, but the prevalence of systemic lupus erythematosus is significantly increased in people with additional X chromosomes.Case presentationWe report a 17-year-old Chinese female patient with systemic lupus erythematosus complicated with trisomy X, accompanied by lupus nephritis, pancytopenia, hemolytic anemia, and multiserous effusion. The patient recovered well after treatment and returned regularly. We review the previously reported cases to summarize the clinical characteristics of these patients.ConclusionThe additional X chromosome is related to the development of systemic lupus erythematosus. Whether it is a subtype of systemic lupus erythematosus remains to be further confirmed.

Interpretable machine learning identifies paediatric Systemic Lupus Erythematosus subtypes based on gene expression data.

Transcriptomic analyses are commonly used to identify differentially expressed genes between patients and controls, or within individuals across disease courses. These methods, whilst effective, cannot encompass the combinatorial effects of genes driving disease. We applied rule-based machine learning (RBML) models and rule networks (RN) to an existing paediatric Systemic Lupus Erythematosus (SLE) blood expression dataset, with the goal of developing gene networks to separate low and high disease activity (DA1 and DA3). The resultant model had an 81% accuracy to distinguish between DA1 and DA3, with unsupervised hierarchical clustering revealing additional subgroups indicative of the immune axis involved or state of disease flare. These subgroups correlated with clinical variables, suggesting that the gene sets identified may further the understanding of gene networks that act in concert to drive disease progression. This included roles for genes (i) induced by interferons (IFI35 and OTOF), (ii) key to SLE cell types (KLRB1 encoding CD161), or (iii) with roles in autophagy and NF-κB pathway responses (CKAP4). As demonstrated here, RBML approaches have the potential to reveal novel gene patterns from within a heterogeneous disease, facilitating patient clinical and therapeutic stratification.

Pearls for the diagnosis and possible pathophysiological mechanisms of valproic acid-induced lupus erythematosus: A literature review.

Background: Drug-induced lupus erythematosus (DILE) accounts for 10-15% of systemic lupus erythematosus (SLE) cases, with more than 100 pharmaceutical agents implicated in its development. Depending on the offending drug, clinical and serological manifestations present great variability and, thus, DILE may be overlooked in clinical practice. Valproic acid (VPA) - induced lupus erythematosus has not been analytically reported in the literature, rendering the recognition of such cases even more difficult.Objective: The aim of this study was to analyze VPA - induced lupus features and to discuss possible pathophysiological mechanisms.Materials and Methods: This literature review was conducted in PubMed and Embase databases in June 2021, in search of DILE cases induced by VPA. We found 164 manuscripts, out of which 140 articles regarding other adverse effects or drugs were discarded. Finally, 15 cases fulfilled the eligibility criteria to be included in this review.Results: Although SLE is more common in females, VPA-induced lupus presented a male predilection. Patients developed DILE within the first three months of treatment with VPA at a percentage of 50%, whereas four patients from one to five years after VPA initiation. DILE frequently presented with mild symptoms. In most patients, serositis manifested with polyarthritis, pleural effusion or pericarditis. Notably, one patient presented with Rowell's syndrome, a rare subtype of lupus erythematosus with erythema multiforme and speckled pattern of antinuclear antibodies (ANAs). Central nervous system, renal and skin involvement was scarcely observed. Cytopenia was noted in 7 patients. Immunological findings included positive ANAs in the vast majority of the patients (86.7%), positive anti-histone antibodies in five, positive anti-dsDNA antibodies in three and hypocomplementemia in two patients. Despite the prompt resolution of clinical symptoms after VPA discontinuation, serological abnormalities persisted up to 18 months. Apart from the discontinuation of VPA administration for the resolution of DILE, treatment included corticosteroids in 8 cases.Conclusion: Valproic acid has been implicated in several cases of DILE. Clinicians should be aware of this entity and recognize it promptly to ensure a favorable outcome. Possible pathophysiologic associations may be extrapolated, but a clearer understanding of this syndrome is to be gained by further studies.

B Cell Signatures Distinguish Cutaneous Lupus Erythematosus Subtypes and the Presence of Systemic Disease Activity.

Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin disease characterized by a diverse cadre of clinical presentations. CLE commonly occurs in patients with systemic lupus erythematosus (SLE), and CLE can also develop in the absence of systemic disease. Although CLE is a complex and heterogeneous disease, several studies have identified common signaling pathways, including those of type I interferons (IFNs), that play a key role in driving cutaneous inflammation across all CLE subsets. However, discriminating factors that drive different phenotypes of skin lesions remain to be determined. Thus, we sought to understand the skin-associated cellular and transcriptional differences in CLE subsets and how the different types of cutaneous inflammation relate to the presence of systemic lupus disease. In this study, we utilized two distinct cohorts comprising a total of 150 CLE lesional biopsies to compare discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE), and acute cutaneous lupus erythematosus (ACLE) in patients with and without associated SLE. Using an unbiased approach, we demonstrated a CLE subtype-dependent gradient of B cell enrichment in the skin, with DLE lesions harboring a more dominant skin B cell transcriptional signature and enrichment of B cells on immunostaining compared to ACLE and SCLE. Additionally, we observed a significant increase in B cell signatures in the lesional skin from patients with isolated CLE compared with similar lesions from patients with systemic lupus. This trend was driven primarily by differences in the DLE subgroup. Our work thus shows that skin-associated B cell responses distinguish CLE subtypes in patients with and without associated SLE, suggesting that B cell function in skin may be an important link between cutaneous lupus and systemic disease activity.

Blood Genomics Identifies Three Subtypes of Systemic Lupus Erythematosus: "IFN-High," "NE-High," and "Mixed".

Purpose Systemic lupus erythematosus (SLE) is a systemic and multifactorial autoimmune disease, and its diverse clinical manifestations affect molecular diagnosis and drug benefits. Our study was aimed at defining the SLE subtypes based on blood transcriptome data, analyzing functional patterns, and elucidating drug benefits. Methods Three data sets were used in this paper that were collected from the Gene Expression Omnibus (GEO) database, which contained two published data sets of pediatric and adult SLE patients (GSE65391, GSE49454) and public longitudinal data (GSE72754) from a cohort of SLE patients treated with IFN-α Kinoid (IFN-K). Based on disease activity scores and gene expression data, we defined a global SLE signature and merged three clustering algorithms to develop a single-sample subtype classifier (SSC). Systematic analysis of coexpression networks based on modules revealed the molecular mechanism for each subtype. Results We identified 92 genes as a signature of the SLE subtypes and three intrinsic subsets (“IFN-high,” “NE-high,” and “mixed”), which varied in disease severity. We speculated that IFN-high might be due to the overproduction of interferons (IFNs) caused by viral infection, leading to the formation of autoantibodies. NE-high might primarily result from bacterial and fungal infections that stimulated neutrophils (NE) to produce neutrophil extracellular traps (NETs) and induced individual autoimmune responses. The mixed type contained both of these molecular mechanisms and showed an intrinsic connection. Conclusions Our research results indicated that identifying the molecular mechanism associated with different SLE subtypes would benefit the molecular diagnosis and stratified therapy. Moreover, repositioning of IFN-K based on subtypes also revealed an improved therapeutic effect, providing a new direction for disease treatment and drug development.

Research in practice: Disturbance in intracellular nucleic acid metabolism promotes lupus erythematosus

Lupus erythematosus (LE) is an autoimmune disease with a broad spectrum of cutaneous manifestations. It is characterized by a loss of tolerance to nuclear antigens, including endogenous nucleic acids, autoantibody formation and upregulation of the typeI interferon pathway. This can be induced by an immune response to unrestricted extracellular self-antigens. In addition, the molecular characterization of rare monogenic subtypes of LE has revealed insights into the role of cell-intrinsic sensing of endogenous self-nucleic acids in inducing a typeI interferon response. This pathway can also initiate and sustain LE. The enhanced understanding of innate and adaptive immune responses in LE is a prerequisite for the development of more targeted therapies.

Dermatologic Manifestations, Histologic Features and Disease Progression among Cutaneous Lupus Erythematosus Subtypes: A Prospective Observational Study in Asians.

IntroductionCutaneous manifestations are central to the primary diagnosis of systemic lupus erythematosus (SLE). However, information on the clinical, histopathologic, and direct immunofluorescence (DIF) features among subtypes of cutaneous lupus erythematosus (CLE), as well as longitudinal prospective observational study to evaluate the natural history and the progression to SLE, is lacking among Asians. Our objectives are to summarize the differences in the clinical, histopathologic, and DIF characteristics and serological profiles between various subtypes of CLE, and to provide its natural history and the association with disease activity in our Asian population.MethodsA prospective observational study on CLE patients was performed between May 2016 and May 2020. Patients underwent full physical/dermatologic examination, skin biopsy for histology, and DIF. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores and laboratory data were evaluated. Time schedule and characteristics for resolution and/or the disease progression to SLE were recorded in subsequent follow-ups.ResultsOf 101 biopsy-proven CLE patients, 25 had acute CLE (ACLE), 8 had subacute CLE (SCLE), 39 had chronic CLE (CCLE) only, 22 had CCLE with SLE, and 7 had LE-nonspecific cutaneous lesions only. Patients with exclusive CLE showed lower female preponderance, serological abnormalities, and correlation to systemic disease. However, when CLE was accompanied with any LE-nonspecific cutaneous manifestations, they were associated with high antinuclear antibody (ANA) titer, renal, hematologic, joint involvement, and greater SLEDAI score. Of 207 biopsy sections, SCLE/CCLE regardless of systemic involvement showed significantly higher percentage of superficial/deep perivascular and perieccrine infiltration than ACLE. On DIF, deposition of multiple immunoreactants was associated with higher systemic disease. Approximately 10% of CLE-only patients later developed SLE but had mild systemic involvement.ConclusionOur findings support that each CLE subtype has a diverse and unique character. Comprehensive understanding of the differences among CLE subtypes is important for achieving the correct diagnosis and providing appropriate disease monitoring and management.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-020-00471-y.

Alendronate induced subacute cutaneous lupus erythematosus successfully treated with intravenous immunoglobulin

The subacute cutaneous lupus erythematosus (SCLE) is a distinct subtype of lupus erythematosus (LE) representing specific clinical and serological features. Almost 20%-30% of the cases with SCLE are predicted to associated with medications. Thiazide diuretics, terbinafine, antiepileptic, and proton pump inhibitors are the best-known drugs to induce drug-related SCLE. Herein we want to present a 65-year-old female with alendronate induced SCLE, resistant to classical therapies, and respond well to intravenous immunoglobulin (IVIG), suggesting that IVIG could be an alternative treatment in patients resistant to classical treatment protocols.

Use of the Cutaneous Lupus Disease Area and Severity Index as an outcome measure in clinical trials: a descriptive study.

This study summarizes the use, since its inception, of the Cutaneous Lupus Disease Area and Severity Index (CLASI) as an outcome measure in clinical studies. We systematically searched the MEDLINE, PubMed, EMBASE and Cochrane databases for papers including the term 'cutaneous lupus disease area and severity index' and its abbreviations up to August 2017, identifying 205 abstracts. Following shortlisting, two independent physicians critically reviewed 71 papers for data extraction. We found that a limited number of high-quality studies used the CLASI scoring as an outcome measure. We concluded that further validation is necessary to identify the effectiveness of the CLASI in the assessment of cutaneous lupus erythematosus subtypes. The use of standardized core patient- and physician-reported outcome measures may reduce heterogeneity and allow comparisons between patients enrolled in clinical trials. This would improve the relevance within clinical practice, where the use of CLASI is currently limited.

Pigmented linear discoid lupus erythematosus following the lines of Blaschko: A retrospective study of a Chinese series.

Linear cutaneous lupus erythematosus is a rare subtype of lupus erythematosus (LE) that develops linear lesions following the lines of Blaschko. Linear cutaneous lupus erythematosus may present as various subtypes of LE, including linear discoid lupus erythematosus. There are few reports about pigmentedlinear discoid lupus erythematosus in the literature. We aimed to summarize the clinical and pathological features of patients with pigmented linear discoid lupus erythematosus following the lines of Blaschko. Eighteen patients with pigmented linear discoid lupus erythematosus attending the outpatient department of the Dermatology, Peking Union Medical College Hospital, China, were enrolled in the study. We recorded clinical data including sex, age at onset, disease duration, location and distribution of the lesions, symptoms, trigger factors, antinuclear antibody (ANA) testing, therapy, and therapeutic responses. Histopathological features were also summarized. All 18 patients presented with well-defined brownish pigmented linear or segmental macules or plaques, following the lines of Blaschko. All the lesions were located on the head or neck. Unilaterally distributed lesions were found in 94.4% of patients. Two patients showed low titers of ANA in a speckled pattern. No systemic involvement or progression to systemic LE was noted. The patients were clinically diagnosed as pigmented lichen planus (55.6%), pigmented linear discoid lupus erythematosus (33.3%), and linear morphea (11.1%) before histopathological examination. The study was retrospective and direct immunofluorescence was not performed. Not all patients' information was available and 4 patients were lost to follow-up because their contact information was changed. Pigmented linear discoid lupus erythematosus mostly occurs on the head and neck. It manifests as brownish macules along the lines of Blaschko. Differentiation between pigmented linear discoid lupus erythematosus and other dermatoses that have a linear distribution can be difficult both clinically and pathologically, but histological details can help distinguish them.

Investigating the presence of neutrophil extracellular traps in cutaneous lesions of different subtypes of lupus erythematosus

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, little is known about the implication of NETs in cutaneous lupus. In this case series of 30 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different subtypes of lupus (5 with discoid lupus or DLE, 5 with subacute cutaneous lupus or SCLE, 11 with acute cutaneous SLE, 7 with lupus panniculitis and 2 with chilblains). Immunofluorescence was performed on formalin-fixed paraffin-embedded skin biopsies using antibodies against neutrophilic granules (elastase, myeloperoxidase, PR-3 proteins and citrullinated histone 3). Dihydroethidium staining was performed to detect reactive oxygen species (ROS), known inducers of NETs. NETs were detected in the different subtypes of cutaneous lupus as well as in cutaneous lesions of SLE. The amounts of neutrophils producing NETs were significantly higher in lupus panniculitis (49%), acute cutaneous SLE (41%) and DLE (32%), in comparison with SCLE (5%) and chilblains (0%). This suggests that NETs might be associated with more tissue damage and scarring. ROS were observed in the different cutaneous subtypes of lupus independent of NETs.

Varied responses to and efficacies of hydroxychloroquine treatment according to cutaneous lupus erythematosus subtypes in Japanese patients.

Hydroxychloroquine is recommended as the first-line systemic treatment for cutaneous lupus erythematosus (CLE) in Western countries, and it was approved in Japan in 2016. However, the efficacy of hydroxychloroquine in various cutaneous lupus erythematosus subtypes in Japanese patients has not been elucidated to date. Therefore, we investigated the efficacy of hydroxychloroquine for the treatment of cutaneous manifestations according to CLE subtypes in Japanese patients. We enrolled 35 patients (29 diagnosed with systemic lupus erythematosus and six with CLE) in this retrospective study. We analyzed the efficacy of hydroxychloroquine for the treatment of cutaneous manifestations according to cutaneous lupus erythematosus subtypes, time to the first skin improvement, as well as effects on laboratory data and reduction of concomitant immunosuppressive drug administration at 16 and 32weeks of therapy. Complete improvement was observed at high rates for acute CLE (ACLE); however, partial or non-improvement rates were higher for chronic CLE (CCLE) at 16weeks. Several patients with alopecia without scarring achieved complete improvement at 32weeks. CCLE tended to take more time to improve than ACLE. Overall, hydroxychloroquine was highly effective for skin: 87% of patients had at least some beneficial response at 16weeks. Nevertheless, there were wide variations in complete improvement rates and duration for improvement among CLE subtypes. Our findings suggest that a therapeutic approach considering the subtypes of CLE will improve its management.