Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions

American Journal of Clinical Dermatology, Journal Year: 2023, Volume and Issue: 24(4), P. 521 - 540

Published: May 4, 2023

Lupus erythematosus comprises a spectrum of autoimmune diseases that may affect various organs (systemic lupus [SLE]) or the skin only (cutaneous [CLE]). Typical combinations clinical, histological and serological findings define clinical subtypes CLE, yet there is high interindividual variation. Skin lesions arise in course triggers such as ultraviolet (UV) light exposure, smoking drugs; keratinocytes, cytotoxic T cells plasmacytoid dendritic (pDCs) establish self-perpetuating interplay between innate adaptive immune system pivotal for pathogenesis CLE. Therefore, treatment relies on avoidance UV protection, topical therapies (glucocorticosteroids, calcineurin inhibitors) rather unspecific immunosuppressive immunomodulatory drugs. Yet, advent licensed targeted SLE might also open new perspectives management The heterogeneity CLE be attributable to individual variables we speculate prevailing inflammatory signature defined by either cells, B pDCs, strong lesional type I interferon (IFN) response, above suitable predict therapeutic response treatment. pretherapeutic assessment infiltrate could stratify patients with refractory T-cell-directed (e.g. dapirolizumab pegol), B-cell-directed belimumab), pDC-directed litifilimab) IFN-directed anifrolumab). Moreover, Janus kinase (JAK) spleen tyrosine (SYK) inhibitors broaden armamentarium near future. A close interdisciplinary exchange rheumatologists nephrologists mandatory optimal best strategy.

Language: Английский

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Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: a large-scale, propensity-matched global retrospective cohort study

EBioMedicine, Journal Year: 2023, Volume and Issue: 93, P. 104639 - 104639

Published: June 6, 2023

Autoimmune skin diseases can expedite various systemic sequelae involving other organs. Although limited to the skin, cutaneous lupus erythematosus (CLE) was noted be associated with thromboembolic diseases. However, small cohort sizes, partially discrepant outcomes, missing data on CLE subtypes, and incomplete risk assessment limits these findings.The Global Collaborative Network of TriNetX provides access medical records more than 120 million patients worldwide. We used elucidate for cardiac vascular after diagnosis CLE, its subtypes chronic discoid (DLE) subacute (SCLE). included 30,315 27,427 DLE, 1613 SCLE patients. performed propensity-matched studies determining develop (ICD10CM:I00-99) following or SCLE. Patients were excluded.We document that subtype DLE but less so are a higher This predominantly events such as pulmonary embolism, cerebral infarction, acute myocardial also peripheral disease pericarditis. For example, hazard ratio arterial embolism thrombosis 1.399 (confidence interval: 1.230-1.591, p < 0.0001) diagnosis. The study is by retrospective collection reliance ICD10-disease classification.CLE major an increased development wide range diseases.This research funded Deutsche Forschungsgemeinschaft (EXC 2167, CSSL/CS01-2022) Excellence-Chair Program State Schleswig-Holstein.

Language: Английский

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The Spectrum of Cutaneous Manifestations in Lupus Erythematosus: A Comprehensive Review

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(8), P. 2419 - 2419

Published: April 21, 2024

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

Language: Английский

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Deucravacitinib zeigt eine höhere Wirksamkeit und Sicherheit bei kutanem Lupus erythematodes im Vergleich zu verschiedenen Biologika und niedermolekularen Wirkstoffen: systematische Übersicht und Metaanalyse

Kompass Autoimmun, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: April 10, 2025

Hintergrund: Neue Therapien für den kutanen Lupus erythematodes (CLE) und systemischen (SLE) haben in früheren Studien ihre Wirksamkeit Sicherheit gezeigt. Es fehlen jedoch vergleichende Daten zu diesen Therapien, was Integration die klinische Praxis einschränkt. Unser Ziel ist es daher, eine systematische Übersicht Netzwerk-Metaanalyse durchzuführen, um neuer systemischer bei CLE vergleichen. Methoden: Eine Recherche PubMed, Embase CENTRAL wurde am 25. November 2023 durchgeführt, Patienten mit oder SLE aktiver kutaner Beteiligung identifizieren, neuen behandelt wurden. Die primären Outcomes waren der Anteil Patienten, Cutaneous Erythematosus Disease Area and Severity Index-50 (CLASI50) erreichten, Veränderung des CLASI-A das Auftreten von unerwünschten Ereignissen (AE) schwerwiegenden (SAE). Ergebnisse: wurden 18 280 Datensätze abgerufen, denen 53 Einschlusskriterien erfüllten. Deucravacitinib zeigte signifikant höhere hinsichtlich Erreichens CLASI50 im Vergleich Placebo (Odds Ratio (OR): 8,28, 95%-Konfidenz­intervall (KI): 2,22–30,91). Auch Litifilimab (OR: 2,54, 95%-KI: 1,20–5,40) Anifrolumab 2,25, 1,23–4,14) wirksamer als ein Placebo. gab keine signifikanten Unterschiede Häufigkeit AE SAE zwischen Behandlungen dem Schlussfolgerung: sind wirksame sichere Behandlungsoptionen CLE. überlegene weniger AE. CLE, unzureichend auf Erst- Zweitlinientherapie angesprochen haben, könnten Aufnahme ihr Behandlungsschema profitieren.

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Aberrant inflammasome activation as a driving force of human autoimmune skin disease

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 30, 2023

Autoimmune skin diseases are understood as conditions in which the adaptive immune system with autoantigen-specific T cells and autoantibody-producing B reacting against self-tissues plays a crucial pathogenic role. However, there is increasing evidence that inflammasomes, large multiprotein complexes were first described 20 years ago, contribute to autoimmune disease progression. The inflammasome its contribution bioactivation of interleukins IL-1β IL-18 play an essential role combating foreign pathogens or tissue damage, but may also act driver myriad chronic inflammatory when dysfunctionally regulated. Inflammasomes containing NOD-like receptor family members NLRP1 NLRP3 well AIM2-like member AIM2 have been increasingly investigated conditions. In addition autoinflammatory diseases, often associated involvement, aberrant activation has implied can either affect besides other organs such systemic lupus erythematosus sclerosis isolated humans. latter include, among others, T-cell mediated disorders vitiligo, alopecia areata, lichen planus cutaneous autoantibody-driven blistering bullous pemphigoid. Some characterized by both responses psoriasis. Further insights into dysregulation pathways their forming human pathology could potentially offer new field therapeutic options future.

Language: Английский

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Deucravacitinib shows superior efficacy and safety in cutaneous lupus erythematosus compared to various biologics and small molecules – A systematic review and META-analysis

Autoimmunity Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 103723 - 103723

Published: Dec. 1, 2024

Language: Английский

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Cutaneous lupus erythematosus induced by tislelizumab

JDDG Journal der Deutschen Dermatologischen Gesellschaft, Journal Year: 2024, Volume and Issue: 22(7), P. 1003 - 1004

Published: April 28, 2024

Language: Английский

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

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 10, 2022

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

Language: Английский

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Nano‐encapsulated anandamide reduces inflammatory cytokines in vitro and lesion severity in a murine model of cutaneous lupus erythematosus

Experimental Dermatology, Journal Year: 2023, Volume and Issue: 32(12), P. 2072 - 2083

Published: Sept. 19, 2023

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

Language: Английский

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A lupus erythematosus panniculitis lefolyásának jellegzetességei 17 betegünk retrospektív vizsgálata alapján

Orvosi Hetilap, Journal Year: 2023, Volume and Issue: 164(5), P. 172 - 178

Published: Feb. 5, 2023

Lupus erythematous panniculitis (LEP) is a rare type of chronic cutaneous lupus erythematous. Clinical characteristics are tender, subcutaneous nodules, plaques. Disfigurement face and body might develop which affects the patient's quality life. LEP can be first sign systemic (SLE).Our aim was to review clinicopathological course through our own patients.We retrospectively analyzed clinical records 17 patients at Semmelweis University's Department Dermatology, Venerology Dermatooncology between 2000 2022.The male : female ratio 1 16, average age 37.8 years. Lesion localisations were proximal lower (8/17) upper extremities (7/17), (4/17), breast (3/17), chest (2/17), buttocks back (1/17) distal extremity (1/17). morphologies nodules (11/17), plaques lipoatrophy ulceration calcification Discoid changes covered in 6 cases. In 10 cases, symptoms observed (arthritis haematological (5/17), renal anti-phospholipid syndrome (2/17). 7 fulfilled EULAR/ACR criteria for SLE. Histology showed mixed 8, lobular 3 Average time until diagnosis 24.3 months. Among all SLE patients, skin regressed following immunosuppressive treatment. with only manifestation often resistant therapy erythematous.The takes months or Wider knowledge would shorten diagnosis, preventing disfigurement possible damage internal organs. Based on observations, without treated early immunosuppression. Orv Hetil. 2023; 164(5): 172-178.Bevezetés: A erythematosus cutan krónikus formájának ritka variánsa, klinikailag tömött, subcutan csomók és erythemás plakkok jellemzik. Az aktív tünetek az arcot testet torzító maradványtünetekkel gyógyulhatnak, rontva betegek életminőségét. szisztémás (SLE) részjelensége lehet, első tüneteként kialakulhat. Célkitűzés: klinikopatológiai képének bemutatása saját beteganyagunk szemléltetésével, betegség lefolyásának értékelése. Módszerek: Egyetem Bőr-, Nemikórtani Bőronkológiai Klinikáján 2022 között jelentkezett LEP-betegek összegyűjtése, adataik retrospektív elemzése. Eredmények: beteg közül férfi, 16 nő, átlagéletkoruk 37,8 év volt. Tüneteik leggyakrabban proximalis alsó felső végtagokon jelentkeztek (alsó: 8/17, felső: 7/17), arc 4, emlő 3, mellkas farpofák 2-2, hát lábszár 1-1 esetben volt érintett. csomó illetve plakk 4 lipoatrophia, 3-nál kifekélyesedés, 1-nél kalcifikáció. betegnél tünetet discoid fedte. alakult ki tünet: arthritis hematológiai eltérés veseérintettség antifoszfolipid-szindróma diagnózisát tudtuk felállítani. szövettani kép 8 kevert típusú panniculitist, lobularist mutatott. Átlagosan 24,3 hónap telt el diagnózis felállításáig. SLE-s betegeink bőrtünetei regrediáltak alkalmazott immunszuppresszív kezelésekre. kizárólag bőrmanifesztációt mutató körében gyakori terápiarezisztencia erythematosusban Következtetés: diagnosztizálása több hónapot, évet vehet igénybe. Szélesebb körű ismerete segítheti gyorsabb diagnózisalkotást, megelőzhető maradványtünetek, esetleges belszervi elváltozások kialakulása. Megfigyeléseink alapján nélküli esetén korai terápiát lenne érdemes bevezetni. 172–178.

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