Cutaneous manifestations of systemic lupus erythematosus: experience from a tertiary care hospital of Bangladesh

Background: Systemic lupus erythematosus (SLE) is a chronic, multisystem disorder that can affect any organ of the body. Approximately 80 percent of patients develop skin disease at some point in their disease course. The association with SLE varies among the subtypes of cutaneous lupus erythematosus (LE). Better understanding of cutaneous manifestations can help in more effective management. This study aimed to evaluate the pattern of cutaneous manifestations of SLE and to find out association with organ involvement. Methods: This cross-sectional observational study was conducted in the Green Life Medical College Hospital from January 2019 to December 2020. Sixty four lupus patients who fulfilled the SLICC 2012 classification criteria and having new onset or preexisting skin complaints were enrolled. Mixed connective tissue disease and other overlap syndromes were excluded. All patients were evaluated by a dermatologist and diagnosis was done as per modified Gilliam Classification criteria. Results: Out of 64 patients, 56 were female and 8 were male. Female and male ratio was 7:1. Mean age was 28.4±9.6 years. Among the cutaneous manifestations, LE specific was 38 (59.4%), LE non-specific was 41 (64.1%). Among LE specific, 66% were acute (ACLE), 42% were sub-acute (SCLE) and 37% patients were chronic (CCLE). Among ACLE, 72% had malar rash and 84% had photosensitivity. Among SCLE, most common was papulosqumous (68%). DLE (86%) was the most common CCLE. Among LE non-specific, 85% had non-scarring alopecia, 52% had vascular abnormalities. Most common organ involvement was musculoskeletal (84%), then renal (56%). DLE had negative association with renal involvement [OR (-0.04)]. No other cutaneous manifestations showed any significant association with any other organ involvement. Conclusion: Cutaneous manifestations are important feature in SLE. LE non-specific was more common than LE specific manifestations in this study. Better understanding can help in efficient diagnosis and management. BIRDEM Med J 2022; 12(1): 57-61

EFEITO DOS RAIOS ULTRAVIOLETA FRENTE AO LÚPUS ERITEMATOSO SISTÊMICO E CUTÂNEO: UMA BREVE REVISÃO

Introdução: O Lúpus Eritematoso é uma doença autoimune mediada, principalmente, por autoanticorpos. Esta doença apresenta alta variabilidade sintomatológica, o que torna extremamente difícil o diagnóstico precoce. Além disso, também pode ser encontrado de formas diferentes de acordo com a localização do órgão afetado, tais como: 1) nos órgãos internos, irá desencadear o Lúpus Eritematoso Sistêmico (LES); e 2) no tecido epitelial, desencadeará o Lúpus Eritematoso Cutâneo (LEC)1. O LES afeta, principalmente, os rins, pulmão, coração, cérebro e articulações, tendo sintomatologias distintas apresentada por dores articulares, dores abdominais, dificuldades para respirar, redução das funções renais, convulsões e, em casos raros, tromboses1. O LEC afeta a pele e a maior característica entre os pacientes é a alta sensibilidade ao sol. Esta exposição pode provocar lesões, manchas avermelhadas ou até cicatrizes desfigurantes e profundas2. Objetivo: Realizar um levantamento bibliográfico sobre a fotossensibilidade do Lúpus Eritematoso Sistêmico e do Lúpus Eritematoso Cutâneo frente aos raios ultravioleta (RUV). Métodos: Trata-se de uma revisão de literatura integrativa. Os artigos selecionados foram publicados entre janeiro de 2018 e agosto de 2021 através dos seguintes bancos de dados: PubMed, NCBI, Science Direct, EBSCO e SciELo. Para realizar o levantamento de dados foram utilizados como descritores “Sistemic Lupus Erythematosus and Photosensitivity” e “Cutaneous Lupus Erythematosus and Photosensitivity”. Resultados: Os estudos demonstraram a relação entre a exposição solar em pacientes com lúpus eritematoso (LES e LEC) e o agravo das diferentes sintomatologias, dentre estas: fadiga, artralgia, artrite, febre modera ou intensa, alopecia, insuficiência renal, trombocitopenia, aumento na quantidade de lesões cutâneas e de cicatrizes desfigurantes, dentre outras3. Atualmente, sabe-se que o LEC acomete, aproximadamente, 70% dos pacientes que possuem LES aumentando a incidência no número de óbitos. Entretanto, também foi observado nesses estudos que a vitamina D, além de seu importante papel na homeostase do cálcio, apresenta efeitos imunomoduladores sobre as células do sistema imunológico, especialmente, frente aos linfócitos T e os autoanticorpos4,5. Conclusão: Os raios ultravioleta são capazes de provocar diversos danos em pacientes com LES e LEC. Diante disso, torna-se de extrema importância que os utilizem medidas fotoprotetoras, podendo ser através do uso de protetores solar, roupas com proteção à raios ultravioleta, chapéus, guarda sol e outras. Além disso, foi observado que a vitamina D pode ser bastante benéfica frente a pacientes autoimunes. Entretanto, mais estudos são necessários para elucidar as dúvidas sobre os riscos e benefícios da vitamina D nesses pacientes.

Thalidomide Exerts Anti-Inflammatory Effects in Cutaneous Lupus by Inhibiting the IRF4/NF-ҡB and AMPK1/mTOR Pathways

Thalidomide is effective in patients with refractory cutaneous lupus erythematosus (CLE). However, the mechanism of action is not completely understood, and its use is limited by its potential, severe side-effects. Immune cell subset analysis in thalidomide’s CLE responder patients showed a reduction of circulating and tissue cytotoxic T-cells with an increase of iNKT cells and a shift towards a Th2 response. We conducted an RNA-sequencing study using CLE skin biopsies performing a Therapeutic Performance Mapping System (TMPS) analysis in order to generate a predictive model of its mechanism of action and to identify new potential therapeutic targets. Integrating RNA-seq data, public databases, and literature, TMPS analysis generated mathematical models which predicted that thalidomide acts via two CRBN-CRL4A- (CRL4CRBN) dependent pathways: IRF4/NF-ҡB and AMPK1/mTOR. Skin biopsies showed a significant reduction of IRF4 and mTOR in post-treatment samples by immunofluorescence. In vitro experiments confirmed the effect of thalidomide downregulating IRF4 in PBMCs and mTOR in keratinocytes, which converged in an NF-ҡB reduction that led to a resolution of the inflammatory lesion. These results emphasize the anti-inflammatory role of thalidomide in CLE treatment, providing novel molecular targets for the development of new therapies that could avoid thalidomide’s side effects while maintaining its efficacy.

Development of a working core outcome set for cutaneous lupus erythematosus: a practical approach to an urgent unmet need

ObjectiveThe lack of standardised outcomes and outcome measures for cutaneous lupus erythematosus (CLE) represents a substantial barrier to clinical trial design, comparative analysis and approval of novel investigative treatments. We aimed to develop a working core outcome set (COS) for CLE randomised controlled trials and longitudinal observational studies.MethodsWe conducted a multistage literature review of CLE and SLE studies to generate candidate domains and outcome measures. Domains were narrowed to a working core domain set. Outcome measures for core domains were identified and examined.ResultsProposed core domains include skin-specific disease activity and damage, investigator global assessment (IGA) of disease activity, symptoms (encompassing itch, pain and photosensitivity), health-related quality of life (HRQoL) and patient global assessment (PtGA) of disease activity. Recommended physician-reported outcome measures include the Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and Cutaneous Lupus Activity IGA (CLA-IGA). For the domains of symptoms, HRQoL and PtGA of disease activity, we were unable to recommend one clearly superior instrument.ConclusionThis work represents a starting point for further refinement pending formal consensus activities and more rigorous evaluations of outcome measure quality. In the interim, the proposed working COS can serve as a much-needed guide for upcoming CLE clinical trials.