RESUMO
Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.
Assuntos
Autoanticorpos , Lúpus Eritematoso Discoide , Lúpus Eritematoso Sistêmico , Pele , Humanos , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Discoide/patologia , Feminino , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Autoanticorpos/imunologia , Autoanticorpos/sangue , Pele/patologia , Pele/imunologia , Pele/metabolismo , Adulto , Pessoa de Meia-Idade , Alelos , Antígenos HLA/genética , Antígenos HLA/imunologia , Adulto Jovem , MultiômicaAssuntos
Linfócitos B , Lúpus Eritematoso Discoide , Camundongos Endogâmicos MRL lpr , Pele , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Discoide/patologia , Lúpus Eritematoso Discoide/diagnóstico , Animais , Camundongos , Humanos , Linfócitos B/imunologia , Pele/patologia , Pele/imunologia , Modelos Animais de Doenças , Feminino , Diagnóstico DiferencialRESUMO
Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians' understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions.
Assuntos
Interleucina-10 , Líquen Plano Bucal , Lúpus Eritematoso Discoide , Lesões Pré-Cancerosas , Fator de Necrose Tumoral alfa , Genótipo , Humanos , Testes Imunológicos , Inflamação , Interleucina-10/genética , Interleucina-10/imunologia , Líquen Plano Bucal/genética , Líquen Plano Bucal/imunologia , Lúpus Eritematoso Discoide/genética , Lúpus Eritematoso Discoide/imunologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: 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). OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Interferon-alfa/imunologia , Lúpus Eritematoso Cutâneo/imunologia , Células T de Memória/imunologia , Pele/imunologia , Adulto , Antígenos CD/biossíntese , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/biossíntese , Antígenos de Diferenciação de Linfócitos T/imunologia , Feminino , Humanos , Cadeias alfa de Integrinas/biossíntese , Cadeias alfa de Integrinas/imunologia , Interferon-alfa/farmacologia , Lectinas Tipo C/biossíntese , Lectinas Tipo C/imunologia , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
ABSTRACT: Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets GSE52471 and GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.
Assuntos
Redes Reguladoras de Genes/imunologia , Lúpus Eritematoso Discoide/genética , Quimiocina CXCL10/genética , Biologia Computacional , Citocinas/genética , Proteína DEAD-box 58/metabolismo , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Fator Regulador 7 de Interferon/genética , Helicase IFIH1 Induzida por Interferon/genética , Lúpus Eritematoso Discoide/epidemiologia , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Discoide/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Mapas de Interação de Proteínas/imunologia , Receptores Imunológicos/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Pele/imunologia , Pele/patologia , Software , Ubiquitinas/genética , Regulação para Cima/imunologiaRESUMO
OBJECTIVE: Discoid lupus erythematosus (DLE) is the most common category of chronic cutaneous lupus erythematosus, where the pathological process is proved to be closely associated with immunity. This bioinformatic analysis sought to identify key biomarkers and to perform immune infiltration analysis in the skin biopsy samples of DLE. METHODS: GSE120809, GSE100093, GSE72535, GSE81071 were used as the data source of gene expression profiles, altogether containing 79 DLE samples and 47 normal controls (NC). Limma package was applied to identify differentially expressed genes (DEGs) and additional Gene Ontology (GO) together with The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were done. Protein-protein interaction network (PPI) was constructed using STRING and Cytoscape. Hub genes were selected by CytoHubba. Finally, immune filtration analysis was finished by the CIBERSORT algorithm, and comparisons between the two groups were accomplished. RESULTS: A total of 391 DEGs were identified, which were composed of 57 up-regulated genes and 334 down-regulated genes. GO and KEGG enrichment analyses revealed that DEGs were closely related with different steps in the immune response. Top 10 hub genes included GBP2, HLA-F, IFIT2, RSAD2, ISG15, IFIT1, IFIT3, MX1, XAF1 and IFI6. Immune filtration analysis from CIBERSORT had found that compared with NC, DLE samples had higher percentages of CD8+ T cells, T cells CD4 memory activated, T cells gamma delta, macrophages M1 and lower percentages of T cells regulatory, macrophages M2, dendritic cells resting, mast cells resting, mast cells activated. CONCLUSION: This bioinformatic study selected key biomarkers from the contrast between DLE and NC skin samples and is the first research to analyze immune cell filtration in DLE.
Assuntos
Biomarcadores/metabolismo , Biologia Computacional/métodos , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Discoide/metabolismo , Pele/imunologia , Biópsia/métodos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Regulação para Baixo , Ontologia Genética , Humanos , Lúpus Eritematoso Discoide/patologia , Macrófagos/metabolismo , Mapas de Interação de Proteínas/genética , Pele/patologia , Linfócitos T Reguladores/metabolismo , Transcriptoma/genética , Regulação para CimaRESUMO
BACKGROUND: Age at disease onset may modulate systemic lupus erythematosus (SLE), but its relation to cutaneous/extracutaneous manifestation remains understudied. OBJECTIVE: To compare the cutaneous, systemic features, laboratory characteristics, and disease severity between late- and adult-onset SLE patients. METHODS: Analyses of the cutaneous, systemic involvement, laboratory investigations, SLE disease activity index 2000 (SLEDAI-2K), and disease damage were performed to compare between groups. RESULTS: Of 1006 SLE patients, 740 and 226 had adult- (15-50 years) and late-onset (>50 years), respectively. Among 782 with cutaneous lupus erythematosus (CLE), acute CLE (ACLE) and chronic CLE (CCLE) were more common in the adult- and late-onset SLE, respectively (p = 0.001). Multivariable logistic regression analysis demonstrated that male patients and skin signs, including papulosquamous subacute CLE, discoid lupus erythematosus, and lupus profundus, were associated with late-onset SLE (all p < 0.05). Late-onset SLE had lower lupus-associated autoantibodies, and systemic involvement (all p < 0.05). ACLE, CCLE, mucosal lupus, alopecia, and non-specific lupus were related to higher disease activity in adult-onset SLE (all p < 0.001). There was no difference in the damage index between the two groups. CONCLUSIONS: Late-onset SLE had a distinct disease expression with male predominance, milder disease activity, and lower systemic involvement. Cutaneous manifestations may hold prognostic values for SLE.
Assuntos
Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Cutâneo/patologia , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Discoide/patologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Doença Aguda , Adulto , Idade de Início , Idoso , Alopecia/diagnóstico , Alopecia/etiologia , Alopecia/imunologia , Autoanticorpos/sangue , Técnicas de Laboratório Clínico/estatística & dados numéricos , Técnicas de Laboratório Clínico/tendências , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Tailândia/epidemiologiaAssuntos
Pérnio , Clobetasol/administração & dosagem , Temperatura Baixa/efeitos adversos , Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Discoide/complicações , Lúpus Eritematoso Sistêmico/complicações , Pele/patologia , Administração Tópica , Adulto , Biópsia/métodos , Pérnio/diagnóstico , Pérnio/tratamento farmacológico , Pérnio/etiologia , Pérnio/prevenção & controle , Feminino , Glucocorticoides/administração & dosagem , Humanos , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Cutâneo/etiologia , Lúpus Eritematoso Cutâneo/prevenção & controle , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Resultado do TratamentoAssuntos
Anti-Inflamatórios/efeitos adversos , Produtos Biológicos/efeitos adversos , Lúpus Eritematoso Discoide/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Humanos , Lúpus Eritematoso Discoide/induzido quimicamente , Lúpus Eritematoso Discoide/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Psoríase/tratamento farmacológico , Psoríase/imunologia , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/imunologia , Fator de Necrose Tumoral alfa/imunologiaAssuntos
Alopecia/patologia , Células Epiteliais/patologia , Folículo Piloso/patologia , Queratina-15/metabolismo , Células-Tronco/patologia , Cicatriz/diagnóstico , Cicatriz/patologia , Células Epiteliais/ultraestrutura , Fibrose/diagnóstico , Fibrose/patologia , Folículo Piloso/ultraestrutura , Humanos , Líquen Plano/imunologia , Líquen Plano/patologia , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Discoide/patologia , Microscopia de Fluorescência/métodos , Células-Tronco/citologia , Células-Tronco/imunologiaAssuntos
Alopecia/etiologia , Alopecia/patologia , Lúpus Eritematoso Discoide/complicações , Adulto , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Anticorpos Antinucleares/imunologia , Antimaláricos/uso terapêutico , Biópsia , Cicatriz/patologia , Derme/patologia , Dermoscopia/métodos , Feminino , Fibrose/patologia , Humanos , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Discoide/imunologia , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Alopecia/diagnóstico , Dermoscopia , Folículo Piloso/diagnóstico por imagem , Lúpus Eritematoso Discoide/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/imunologia , Alopecia/patologia , Biópsia , Estudos Transversais , Feminino , Folículo Piloso/patologia , Humanos , Lúpus Eritematoso Discoide/imunologia , Masculino , Pessoa de Meia-IdadeAssuntos
Dessensibilização Imunológica/métodos , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Discoide/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Toxidermias/diagnóstico , Toxidermias/imunologia , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the profiles of anti-RPLP0, anti-galectin3 antibodies, interferon-α (IFN-α), interferon-λ1(IFN-λ1) and interleukin-17A/F(IL-17A/F) in the subtypes of cutaneous lupus erythematosus (CLE) including acute CLE (ACLE), subacute CLE (SCLE) and discoid lupus erythematosus (DLE). METHODS: Serum levels of autoantibodies and cytokines were determined by enzyme-linked immunoabsorbent assay (ELISA). Lupus lesions were evaluated by cutaneous lupus erythematosus disease area and severity index (CLASI). RESULTS: Serum anti-RPLP0, anti-galectin3 antibodies and IFN-λ1 were higher in systemic lupus erythematosus (SLE) patients with skin lesions than those without skin lesions, compared to healthy controls. IFN-α, IL-17A and IL-17F was elevated in all patients regardless of skin lesions. The two antibodies, IFN-α and IL-17A were positively correlated with the CLASI score in all patients with CLE. In addition, serum IL-17A was positively correlated to the CLASI score of ACLE, SCLE and DLE, while anti-RPLP0 and anti-galectin3 antibodies were only correlated to the score of SCLE and IL-17F to DLE. CONCLUSION: Serum anti-RPLP0, anti-galectin3 antibodies, IFN-α, IFN-λ1 and IL-17A/F are associated with the occurrence of lupus skin lesions regardless of the systemic complications, whereas the profiles of these inflammatory mediators vary with the subtypes of lupus skin lesions.
Assuntos
Autoanticorpos/sangue , Interferons/sangue , Interleucina-17/sangue , Lúpus Eritematoso Cutâneo/sangue , Lúpus Eritematoso Cutâneo/imunologia , Adulto , Autoanticorpos/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Interferons/imunologia , Interleucina-17/imunologia , Lúpus Eritematoso Discoide/sangue , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Índice de Gravidade de Doença , Pele/imunologia , Pele/metabolismoRESUMO
INTRODUCTION: Disease features and laboratory abnormalities differ among adult-onset and childhood-onset systemic lupus erythematosus (aSLE and cSLE). Socioeconomic status both independent of, and in combination with, ethnicity influences the disease phenotype and outcome. OBJECTIVE: To compare the various disease features among patients with cSLE and aSLE in a limited monetary income Egyptian cohort attending a large free-of-charge university hospital. Patients and methods: Retrospective analysis of the medical records of 714 SLE patients attending Cairo University Hospitals from January 2000 to December 2019. Of them 602 (400 with aSLE and 202 with cSLE) were enrolled in the study. RESULTS: The mean age of disease onset was 28.27 ± 10.55 among aSLE patients compared to 12.88 ± 4.26 years among cSLE patients. Disease duration was 12.03 ± 5.05 and 4.14 ± 3.18 years in aSLE and cSLE, respectively. Female to male ratio was 15:1 among patients with aSLE, as compared to 2.67:1 among cSLE (<0.001). Arthritis (69%), oral ulcers (48.5%), neuropsychiatric (18.3%) and thrombotic manifestations of antiphospholipid syndrome (12%) were significantly more frequent in aSLE. On the other hand, renal (67.8%), serositis (49.6%), fever (49%), lymphopenia (40.6%), hemolytic anemia (38.6%), and discoid lupus (13.4%) were significantly more frequent in cSLE. Weight loss, malar rash, photosensitivity, thrombocytopenia, leucopenia and lymphadenopathy were not significantly different between the two groups. Hypocomplementemia, proteinuria, urinary sediments, hematuria were significantly more frequent in cSLE. For those patients with renal involvement, who underwent renal biopsy (58.3% in aSLE and 63.5% in cSLE), there was no significant difference with regard to the different histopathological classes. Anti-Smith, anti-cardiolipin antibodies and rheumatoid factor were significantly more frequent among aSLE patients, while anti-La antibodies were more frequent among cSLE patients. CONCLUSION: Arthritis was the most common clinical manifestation over time in aSLE compared to renal involvement in cSLE. Renal disease tends to be more active in cSLE. The differences in disease manifestations between this cohort and other studies can be attributed to the ethnic and socioeconomic disparities.
Assuntos
Lúpus Eritematoso Discoide/patologia , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/patologia , Adolescente , Adulto , Idade de Início , Anemia Hemolítica/epidemiologia , Anticorpos Antinucleares/sangue , Criança , Comorbidade , Progressão da Doença , Egito/epidemiologia , Feminino , Febre/epidemiologia , Hospitais Universitários , Humanos , Lúpus Eritematoso Discoide/epidemiologia , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/imunologia , Linfopenia/epidemiologia , Masculino , Estudos Retrospectivos , Serosite/epidemiologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
A 6-year-old boy presented with dusky erythematous plaques in linear and whorled pattern over limbs and trunk for the past 1 year along with subcutaneous nodule on the left cheek of 3 months duration. He also had Gottron-like and inverse Gottron-like papules on hands. Histology from truncal lesion showed interface dermatitis with superficial and deep perivascular and periappendageal infiltrate suggestive of discoid cutaneous lupus erythematosus (CLE), while biopsy from facial nodule revealed features of lupus panniculitis. The connective tissue disease workup showed only antinuclear antibody positivity (2+, 1:100 dilution). There was no clinical or investigational evidence of myositis as part of dermatomyositis (DM) workup. A final diagnosis of Blaschko-linear CLE was made, since Gottron-like and inverse Gottron-like papules can be found in CLE as well. The present case highlights the rarity of presentation of CLE along Blaschko lines and overlapping features of Blaschko-linear CLE with DM.
Assuntos
Anticorpos Antinucleares/sangue , Dermatomiosite , Lúpus Eritematoso Discoide , Paniculite de Lúpus Eritematoso/patologia , Pele/patologia , Biópsia/métodos , Criança , Dermatomiosite/diagnóstico , Dermatomiosite/patologia , Diagnóstico Diferencial , Humanos , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Discoide/patologia , MasculinoRESUMO
PURPOSE OF REVIEW: Lupus erythematosus (LE) is characterized by broad and varied clinical forms ranging from a localized skin lesion to a life-threatening form with severe systemic manifestations. The overlapping between cutaneous LE (CLE) and systemic LE (SLE) brings difficulties to physicians for early accurate diagnosis and sometimes may lead to delayed treatment for patients. We comprehensively review recent progress about the similarities and differences of the main three subsets of LE in pathogenesis and immunological mechanisms, with a particular focus on the skin damage. RECENT FINDINGS: Recent studies on the mechanisms contributing to the skin damage in lupus have shown a close association of abnormal circulating inflammatory cells and abundant production of IgG autoantibodies with the skin damage of SLE, whereas few evidences if serum autoantibodies and circulating inflammatory cells are involved in the pathogenesis of CLE, especially for the discoid LE (DLE). Till now, the pathogenesis and molecular/cellular mechanism for the progress from CLE to SLE are far from clear. But more and more factors correlated with the differences among the subsets of LE and progression from CLE to SLE have been found, such as the mutation of IRF5, IFN regulatory factors and abnormalities of plasmacytoid dendritic cells (PDCs), Th1 cells, and B cells, which could be the potential biomarkers for the interventions in the development of LE. A further understanding in pathogenesis and immunological mechanisms for skin damage in different subsets of LE makes us think more about the differences and cross-links in the pathogenic mechanism of CLE and SLE, which will shed a light in predictive biomarkers and therapies in LE.
Assuntos
Lúpus Eritematoso Cutâneo/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Pele , Doença Aguda , Progressão da Doença , Humanos , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/genética , Lúpus Eritematoso Cutâneo/microbiologia , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Discoide/genética , Lúpus Eritematoso Discoide/imunologia , Lúpus Eritematoso Discoide/microbiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/microbiologia , Microbiota/imunologia , Pele/imunologia , Pele/microbiologia , Pele/patologia , Raios Ultravioleta/efeitos adversosRESUMO
The cutaneous manifestations of lupus, especially chronic cutaneous lupus erythematosus, are a source of significant morbidity and can negatively impact patient quality of life. While the active inflammatory component of the disease may be adequately treated, patients are frequently left with residual skin damage and disfiguring aesthetic deficits. Dermatologists lack guidelines regarding the use and safety of various reconstructive and cosmetic interventions in this patient population. Laser treatments are largely avoided in the lupus population because of the possible photodamaging effects of ultraviolet and visible light. Similarly, given the autoimmune nature of this disease, some physicians avoid injectable treatment and grafts because of the concern for disease reactivation via antigenic stimulation. In the second article in this continuing medical education series we compile available data on this topic with the goal of providing evidence-based guidance on the cosmetic treatment of patients with lupus erythematosus with a focus on chronic cutaneous lupus erythematosus.