Systemic lupus erythematosus (SLE) is an autoimmune disease defined by the production of autoantibodies against nuclear antigens in the presence of a wide variety of clinical symptoms. SLE has a peak incidence between the ages of 15 and 40, making it one of the most frequent autoimmune illnesses in women of reproductive age. However, SLE can affect all age groups, from infants to geriatric patients. SLE occurs worldwide but appears to be uncommon on the African continent. It is surprisingly prevalent in African descendants. Although the specific etiology and pathogenesis of SLE are unknown, it is believed to be the result of complicated multifactorial interactions involving genetic, epigenetic, environmental, and hormonal variables that ultimately result in a loss of self-tolerance. As a result, the disease can damage almost every tissue or organ system, with varied duration and severity ranging from moderate to potentially lethal. Autoantibodies of a wide variety can be detected in patients with SLE and are frequently related to distinct clinical features. Antinuclear antibodies (ANA) are detected in 98% of cases but are nonspecific. Contrarily, antibodies to double-stranded DNA (dsDNA), anti-Sm, or anti-nucleosome are particular. Three different patterns of disease activity have been identified: remitting-relapsing disease with flares and intervals of remission, persistently active disease, and extended periods of quiescence. Organ damage, which can occur due to disease activity or even in individuals with no symptoms, is the primary predictor of morbidity and mortality. SLE is a more active area of investigation and therapy innovation than it has ever been. Numerous genes associated with rare monogenic variations of SLE have significantly improved our understanding of the disease's pathogenesis. Additional advances have enabled the identification of novel pathways and a broader range of possible therapeutic targets. Regardless of tremendous improvements in the disease's general prognosis over the last few decades, the burden of renal impairment, infection, and cardiovascular diseases continues to be unacceptably high. A significant proportion of patients, particularly those with lupus nephritis, do not respond to standard of care treatment, although the number of alternative drugs available for therapy switching is limited. Infections are one of the most common consequences of SLE and continue to be a leading cause of morbidity and mortality throughout the disease's course. Current immunization strategies, however, may be insufficient to achieve adequate immunization. Numerous studies indicate that therapy response in SLE is age, gender, ethnicity, genetic, and pharmacokinetic dependent. Thus, the treatment of SLE should gradually transition from standardized therapy to an individualized therapeutic strategy based on the unique characteristics of each patient. There are no standardized guidelines for evaluating therapy responses, making evaluating possible SLE interventional therapies challenging. Conventional therapy such as corticosteroids, hydroxychloroquine, and immunosuppressive drugs improved prognosis significantly. Numerous biologicals, including anifrolumab and ustekinumab, are currently undergoing clinical studies. Belimumab, an antibody targeted against a B cell-activating factor that is a member of the tumor necrosis factor family (BAFF), is currently the only biological medication approved for SLE treatment. In conclusion, management of SLE remains hard, as many biological medicines remain in the research phase, and novel drugs are still undergoing safety and efficacy evaluations. Further study into SLE is expected to result in more specific pathophysiology and tailored therapy in the future.
Il lupus eritematoso sistemico (LES) è una malattia autoimmune caratterizzata dalla produzione di autoanticorpi contro gli antigeni nucleari in presenza di un'ampia varietà di sintomi clinici. Il LES ha un picco di incidenza tra i 15 e i 40 anni, il che lo rende una delle malattie autoimmuni più frequenti nelle donne in età riproduttiva. Tuttavia, il LES può colpire tutti i gruppi di età, dai neonati ai pazienti geriatrici. Il LES si verifica in tutto il mondo, ma sembra essere poco comune nel continente africano. Sorprendentemente è prevalente nelle persone di origine africana. Sebbene l'eziologia specifica e la patogenesi del LES siano sconosciute, si ritiene che sia il risultato di complicate interazioni multifattoriali che coinvolgono variabili genetiche, epigenetiche, ambientali e ormonali che alla fine risultano in una perdita di auto-tolleranza. Di conseguenza, la malattia può danneggiare quasi ogni tessuto o organo, con durata e gravità variabili che vanno da moderate a potenzialmente letali. Autoanticorpi di un'ampia varietà possono essere rilevati nei pazienti con il LES e sono frequentemente correlati a caratteristiche cliniche distinte. Gli anticorpi antinucleo (ANA) vengono rilevati nel 98% dei casi ma sono aspecifici. Al contrario, gli anticorpi contro il DNA a doppio filamento (dsDNA), anti-Sm, o anti-nucleosoma sono particolari. Sono stati identificati tre diversi modelli di attività della malattia: malattia remittente-recidivante, malattia persistentemente attiva e lunghi periodi di quiescenza. Il danno agli organi, che può verificarsi a causa del decorso della malattia o anche in individui senza sintomi, è il principale fattore predittivo di morbilità e mortalità. Il LES è un'area di ricerca e innovazione terapeutica più attiva che mai. Numerosi geni associati a rare varianti monogeniche del LES hanno migliorato significativamente la nostra comprensione della patogenesi della malattia. Ulteriori progressi hanno permesso di identificare nuovi percorsi e una gamma più ampia di possibili obiettivi terapeutici. Nonostante gli enormi miglioramenti nella prognosi generale della malattia negli ultimi decenni, il carico dato dall’insufficienza renale, infezioni e malattie cardiovascolari continua ad essere inaccettabilmente alto. Una percentuale significativa di pazienti, in particolare quelli con nefrite lupica, non risponde al trattamento standard di cura, anche se il numero di farmaci alternativi disponibili per il cambio di terapia è limitato. Le infezioni sono una delle conseguenze più comuni del LES e continuano ad essere una delle principali cause di morbilità e mortalità nel corso della malattia. Le attuali strategie di immunizzazione, tuttavia, possono risultare insufficienti. Numerosi studi indicano che la risposta alla terapia nel LES dipende da età, sesso, etnia, genetica e farmacocinetica. Quindi, il trattamento del LES dovrebbe gradualmente passare da una terapia standardizzata a una strategia terapeutica individualizzata basata sulle caratteristiche uniche di ogni paziente. Non ci sono linee guida standardizzate per la valutazione delle risposte terapeutiche, il che rende impegnativa la valutazione delle possibili terapie interventistiche del LES. La terapia convenzionale come i corticosteroidi, l'idrossiclorochina e i farmaci immunosoppressori hanno migliorato significativamente la prognosi. Numerosi farmaci biologici, tra cui anifrolumab e ustekinumab, sono attualmente oggetto di studi clinici. Belimumab, un anticorpo mirato contro un fattore di attivazione delle cellule B è attualmente l'unico farmaco approvato per il trattamento del LES. In conclusione, la gestione del LES rimane difficile, poiché molti medicinali biologici rimangono in fase di ricerca e i nuovi farmaci sono ancora in fase di valutazione della sicurezza e dell'efficacia. Ulteriori studi sul LES dovrebbero portare in futuro a una fisiopatologia più specifica e a una terapia su misura.
Lupus eritematoso sistemico: una sfida terapeutica
HODO, FRANCESCA
2020/2021
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease defined by the production of autoantibodies against nuclear antigens in the presence of a wide variety of clinical symptoms. SLE has a peak incidence between the ages of 15 and 40, making it one of the most frequent autoimmune illnesses in women of reproductive age. However, SLE can affect all age groups, from infants to geriatric patients. SLE occurs worldwide but appears to be uncommon on the African continent. It is surprisingly prevalent in African descendants. Although the specific etiology and pathogenesis of SLE are unknown, it is believed to be the result of complicated multifactorial interactions involving genetic, epigenetic, environmental, and hormonal variables that ultimately result in a loss of self-tolerance. As a result, the disease can damage almost every tissue or organ system, with varied duration and severity ranging from moderate to potentially lethal. Autoantibodies of a wide variety can be detected in patients with SLE and are frequently related to distinct clinical features. Antinuclear antibodies (ANA) are detected in 98% of cases but are nonspecific. Contrarily, antibodies to double-stranded DNA (dsDNA), anti-Sm, or anti-nucleosome are particular. Three different patterns of disease activity have been identified: remitting-relapsing disease with flares and intervals of remission, persistently active disease, and extended periods of quiescence. Organ damage, which can occur due to disease activity or even in individuals with no symptoms, is the primary predictor of morbidity and mortality. SLE is a more active area of investigation and therapy innovation than it has ever been. Numerous genes associated with rare monogenic variations of SLE have significantly improved our understanding of the disease's pathogenesis. Additional advances have enabled the identification of novel pathways and a broader range of possible therapeutic targets. Regardless of tremendous improvements in the disease's general prognosis over the last few decades, the burden of renal impairment, infection, and cardiovascular diseases continues to be unacceptably high. A significant proportion of patients, particularly those with lupus nephritis, do not respond to standard of care treatment, although the number of alternative drugs available for therapy switching is limited. Infections are one of the most common consequences of SLE and continue to be a leading cause of morbidity and mortality throughout the disease's course. Current immunization strategies, however, may be insufficient to achieve adequate immunization. Numerous studies indicate that therapy response in SLE is age, gender, ethnicity, genetic, and pharmacokinetic dependent. Thus, the treatment of SLE should gradually transition from standardized therapy to an individualized therapeutic strategy based on the unique characteristics of each patient. There are no standardized guidelines for evaluating therapy responses, making evaluating possible SLE interventional therapies challenging. Conventional therapy such as corticosteroids, hydroxychloroquine, and immunosuppressive drugs improved prognosis significantly. Numerous biologicals, including anifrolumab and ustekinumab, are currently undergoing clinical studies. Belimumab, an antibody targeted against a B cell-activating factor that is a member of the tumor necrosis factor family (BAFF), is currently the only biological medication approved for SLE treatment. In conclusion, management of SLE remains hard, as many biological medicines remain in the research phase, and novel drugs are still undergoing safety and efficacy evaluations. Further study into SLE is expected to result in more specific pathophysiology and tailored therapy in the future.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/13780