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1.
Artigo em Inglês | MEDLINE | ID: mdl-31642908

RESUMO

OBJECTIVES: Patients with SLE are often exposed to prolonged immunosuppression since few data on flare recurrence in remitted patients who discontinued immunosuppressants are available. We aimed to assess the rate and predictors of flare after immunosuppressant withdrawal in SLE patients in remission. METHODS: SLE patients diagnosed between 1990 and 2018 (according to the ACR criteria), ever treated with immunosuppressants and currently in follow-up were considered. Immunosuppressant discontinuation was defined as complete withdrawal of any immunosuppressive drug. Reasons for discontinuation were remission, defined as clinical SLEDAI-2K = 0 on a stable immunosuppressive and/or antimalarial therapy and/or on prednisone ⩽5 mg/day, or poor adherence/intolerance. Flares were defined according to the SLEDAI Flare Index. Predictors of a subsequent flare were analysed by multivariate logistic regression. RESULTS: There were 319 eligible patients out of 456 (69.9%). Of the 319 patients, 139 (43.5%) discontinued immunosuppressants, 105 (75.5%) due to remission, 34 (24.5%) due to poor adherence/intolerance. The mean (s.d.) follow-up time after immunosuppressant withdrawal was 91 (71) months (range 6-372). Among the patients who discontinued immunosuppressants, 26/105 remitted (24.7%) and 23/34 unremitted patients (67.6%) experienced a flare (P < 0.001) after a median (range) follow-up of 57 (6-264) and 8 months (1-72), respectively (P = 0.009). In patients who discontinued immunosuppressants due to remission, maintenance therapy with antimalarials (OR 0.243, 95% CI 0.070, 0.842) and the duration of remission at immunosuppressant discontinuation (OR 0.870, 0.824-0.996) were independent protective factors against disease flare. CONCLUSION: SLE flares are not uncommon after immunosuppressant discontinuation, even in remitted patients; however, antimalarial therapy and durable remission can significantly reduce the risk of flare.

2.
Expert Rev Clin Immunol ; 15(6): 617-627, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30933534

RESUMO

INTRODUCTION: Systemic Lupus Erythematosus (SLE) mostly affects women during their childbearing years. Fertility is preserved in SLE patients, but pregnancy is often characterized by a high number of maternal and fetal complications. Adverse pregnancy outcomes (APO) have been widely studied over the last decades and several investigators have focused on the potential clinical and serological predictors of maternal and fetal complications. Areas covered: In this review, we analyzed maternal and fetal complications in SLE patients and predictors of APO. Active disease in the 6 months before conception, lupus nephritis, anti-phospholipid (aPL), anti-SSA/Ro and/or anti-SSB/La antibodies have been identified as the most consistent predictors of maternal and fetal complications to date. However, molecular mechanisms and underlying immunological pathways involved in APO still remain elusive. Expert opinion: Difficulties in assessing prevalence and predictors of APO in SLE patients are due to lack of uniformity in the definitions and methods used in the different studies. In addition, some maternal and fetal complications are difficult to diagnose and to differentiate from each other. Preconception counseling is paramount to prevent APO, and it should consider four main factors: disease activity/lupus nephritis, safety of drugs, aPL, anti-SSA/Ro, and/or anti-SSB/La antibodies.

3.
Exp Biol Med (Maywood) ; 244(2): 120-131, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30669861

RESUMO

IMPACT STATEMENT: Our article focuses on the pathogenesis and treatment of CTD-PAH. In the latest ESC/ESR guidelines for PAH, the authors underline that although CTD-PAH should follow the same treatment protocol as idiopathic PAH, the therapeutic approach is more complex and difficult in the former. This review throws light on several peculiar aspects of CTD-PAH and the latest findings in the pathogenesis, namely, the role of inflammation in the maladaptive right ventricle remodeling in SSc-PAH where immunosuppressants are classically believed to be ineffective. Furthermore, we discuss the major critical points in the therapy of CTD-PAH which is one of the strengths of our article. To the best of our knowledge, there are no other reviews that exclusively focus on the pathogenesis and treatment of CTD-PAH patients, with an emphasis on the more critical issues. Thus, it is our contention that our work would be of interest to the readers.

4.
Exp Biol Med (Maywood) ; 244(1): 42-51, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30664357

RESUMO

IMPACT STATEMENT: Our article is focused on emerging pathogenetic pathways in systemic lupus erythematosus (SLE). Notably, IL-12 and IL-23 have been described as emerging cytokines in SLE pathogenesis. We know that IL-23 stimulates Th17 cells to produce IL-17. We try to point out the importance of IL-23/Th17 axis in SLE and to focus on the interaction between this axis and IL-12. Ustekinumab, a fully human IgG1κ monoclonal antibody directed towards the p40 shared subunit of IL-12 and IL-23, has been recently investigated in SLE, suggesting a potential novel therapeutic strategy in SLE. To our knowledge, there are no reviews which simultaneously focus on IL-12 an IL-23/Th17 axis in SLE. Thus, we believe our work will be of interest to the readers.

5.
Ann Rheum Dis ; 78(3): 365-371, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30626657

RESUMO

OBJECTIVES: To derive and validate a new disease activity measure for systemic lupus erythematosus (SLE), the SLE Disease Activity Score (SLE-DAS), with improved sensitivity to change as compared with SLE Disease Activity Index (SLEDAI), while maintaining high specificity and easiness of use. METHODS: We studied 520 patients with SLE from two tertiary care centres (derivation and validation cohorts). At each visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI 2000 (SLEDAI-2K). To construct the SLE-DAS, we applied multivariate linear regression analysis in the derivation cohort, with PGA as dependent variable. The formula was validated in a different cohort through the study of: (1) correlations between SLE-DAS, PGA and SLEDAI-2K; (2) performance of SLEDAI-2K and SLE-DAS in identifying a clinically meaningful change in disease activity (ΔPGA≥0.3); and (3) accuracy of SLEDAI-2K and SLE-DAS time-adjusted means in predicting damage accrual. RESULTS: The final SLE-DAS instrument included 17 items. SLE-DAS was highly correlated with PGA (r=0.875, p<0.0005) and SLEDAI-2K (r=0.943, p<0.0005) in the validation cohort. The optimal discriminative ΔSLE-DAS cut-off to detect a clinically meaningful change was 1.72. In the validation cohort, SLE-DAS showed a higher sensitivity than SLEDAI-2K (change ≥4) to detect a clinically meaningful improvement (89.5% vs 47.4%, p=0.008) or worsening (95.5% vs 59.1%, p=0.008), while maintaining similar specificities. SLE-DAS performed better in predicting damage accrual than SLEDAI-2K. CONCLUSION: SLE-DAS has a good construct validity and has better performance than SLEDAI-2K in identifying clinically significant changes in disease activity and in predicting damage accrual.

6.
Joint Bone Spine ; 86(4): 475-481, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30579917

RESUMO

OBJECTIVE: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. METHODS: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). RESULTS: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. CONCLUSION: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

7.
Autoimmun Rev ; 18(2): 164-176, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572134

RESUMO

Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes.


Assuntos
Complicações na Gravidez/fisiopatologia , Doenças Reumáticas/fisiopatologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/patologia , Doenças Reumáticas/patologia
8.
Clin Rev Allergy Immunol ; 55(2): 237, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30140999

RESUMO

The following changes are made for this article: (1.) Maddalena Larosa's given name and surname were inadvertently interchanged. The authorgroup section is now corrected. (2.) The author(s)' decision to opt for Open Choice.

9.
Autoimmun Rev ; 17(9): 882-889, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30005860

RESUMO

Scleroderma renal crisis (SRC) is an uncommon but still life-threatening manifestation of systemic sclerosis (SSc). The incidence of SRC has decreased in the last few decades, probably due to a widespread use of vasodilators in SSc patients. It is well-recognized that exposure to different drugs can trigger SRC (corticosteroids, cyclosporine) or might prevent its occurrence (iloprost, calcium channel blockers). The prognosis of this life-threatening manifestation has not substantially improved since 1980s, when ACE-inhibitors were introduced in its treatment. ACE-inhibitors remain the mainstay in the therapy of SRC due to their efficacy in controlling malignant hypertension; indeed, the prognosis largely depends on the rapid improvement of the ongoing renal ischemia. Calcium-channel blockers and in third line diuretics and alpha-blockers should be used as additional therapy if blood pressure control remains suboptimal despite maximum tolerated doses of ACE-inhibitors. Given the growing evidence on the role of complement activation and endothelin-1 in the pathogenesis of SRC, recent case-series and case reports have suggested the use of C5-inhibitors and endothelin receptor antagonists in the therapy of SRC, mainly in the refractory cases. Plasma-exchange seems to give some benefits in patients with SRC and microangiopathy or intolerant to ACE-inhibitors. Renal transplantation is the last treatment option and its outcome is similar to that reported in other connective tissue disorders, with a 5-year patient survival rate of about 82%. In this review we summarize the current knowledge in the treatment of SRC.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Troca Plasmática/métodos , Escleroderma Sistêmico/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Humanos , Prognóstico , Escleroderma Sistêmico/patologia
10.
Ann Rheum Dis ; 77(1): 104-110, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28970217

RESUMO

OBJECTIVE: To evaluate the prevalence, duration and effect on damage accrual of the 'Lupus Low Disease Activity State' (LLDAS) in a monocentric cohort of patients with systemic lupus erythematosus (SLE). METHODS: We studied 293 Caucasian patients with SLE during a 7-year follow-up period. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2K) and SELENA-SLEDAI physician global assessment (PGA), and damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We considered the following definition of LLDAS: SLEDAI-2K ≤4 without major organ activity, no new disease activity, PGA (0-3)≤1, prednisone ≤7.5 mg/day and well-tolerated immunosuppressant dosages. The effect of LLDAS on SDI was evaluated by multivariate regression analysis. We also evaluated remission defined as clinical SLEDAI-2K=0 and prednisone ≤5 mg/day in patients treated with/without stable immunosuppressants and/or antimalarials. RESULTS: LLDAS lasting 1, 2, 3, 4 or ≥5 consecutive years was achieved by 33 (11.3%), 43 (14.7%), 39 (13.3%), 31 (10.6%) and 109 (37.2%) patients, respectively. Patients who spent at least two consecutive years in LLDAS had significantly less damage accrual compared with patients never in LLDAS (p=0.001), and they were significantly less likely to have an increase in SDI (OR 0.160, 95% CI 0.060 to 0.426, p<0.001). On average, 84% of patients in LLDAS also fulfilled the criteria for remission. CONCLUSIONS: LLDAS was associated with a decrease in damage progression in Caucasian patients with SLE. The majority of patients in LLDAS were in remission, which can largely contribute to the protective effect of LLDAS on damage accrual.


Assuntos
Anti-Inflamatórios/uso terapêutico , Progressão da Doença , Lúpus Eritematoso Sistêmico/patologia , Prednisona/uso terapêutico , Índice de Gravidade de Doença , Adulto , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu , Feminino , Seguimentos , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
11.
Autoimmun Rev ; 17(1): 4-10, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29108828

RESUMO

The outcome of lupus nephritis (LN) has changed since the introduction of glucocorticoids (GCs), which dramatically reduced the mortality related to one of the most severe complications of systemic lupus erythematosus (SLE). Since the 1950's, other immunosuppressants, including biologic drugs (i.e. rituximab) have aided in maintaining remission, preserving kidney function, but not preventing treatment-related toxicity. GCs still remain the cornerstone in the treatment of SLE, including LN, and they are widely used in clinical practice. However, GC administration represents a double-edged sword. Indeed, from one side they allow a fast and effective control of disease activity by dampening inflammation; from the other side, they have many and severe side effects leading to organ damage. In this paper, we will discuss pros and cons of the chronic use of GCs, especially focusing on LN.


Assuntos
Corticosteroides/efeitos adversos , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/terapia , Corticosteroides/uso terapêutico , Humanos , Nefrite Lúpica/patologia
12.
J Autoimmun ; 86: 1-8, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28935492

RESUMO

OBJECTIVE: To investigate efficacy, safety and survival of belimumab and to identify predictors of drug response and drug discontinuation in patients with active SLE in clinical practice. PATIENTS AND METHODS: Data of SLE patients, treated with belimumab, from 11 Italian prospective cohorts were analyzed. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-h proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity) were recorded at baseline and every 6 months. SLE Responder Index-4 (SRI-4) was calculated at 12 and 24 months. Demographic and clinical features and comorbidities were included in the univariate and multivariate analysis. Adverse events were recorded at each visit. Statistics was performed using the SPSS software. RESULTS: We studied 188 SLE patients, mean follow-up 17.5 ± 10.6 months. The most frequent manifestations, which required the use of belimumab, were polyarthritis (45.2%) and skin rashes (25.5%). SRI-4 was achieved by 77.0% and 68.7% of patients at 12 and 24-months. Independent predictors of 12-month response were SLEDAI-2K ≥ 10 (OR 40.46, p = 0.001) and polyarthritis (OR 12.64, p = 0.001) and of 24-month response were SLEDAI-2K ≥ 10 (OR 15.97, p = 0.008), polyarthritis (OR 32.36, p = 0.006), and prednisone ≥7.5 mg/day (OR 9.94, p = 0.026). We observed a low rate of severe adverse events. Fifty-eight patients (30.8%) discontinued belimumab after a mean follow-up of 10.4 ± 7.5 months. The drug survival was 86.9%, 76.9%, 69.4%, 67.1%, and 61.9% at 6, 12, 18, 24, and 30 months, respectively. No factors associated with drug discontinuation were found. CONCLUSION: Belimumab is effective and safe when used in clinical practice setting.

14.
Arthritis Care Res (Hoboken) ; 69(1): 115-123, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27390293

RESUMO

OBJECTIVE: To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. METHODS: Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti-double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into "classical" (CLP) and "rheumatoid-like"; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). RESULTS: Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P < 0.001), particularly in those with CLP (P < 0.001), and CLASI decreased in patients with skin manifestation (P = 0.003), either ACLE (P = 0.051) or SCLE (P = 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P = 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation. CONCLUSION: Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
15.
Expert Rev Clin Immunol ; 12(12): 1309-1320, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27362864

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune diseases. Patients with SLE display a wide spectrum of clinical and serological findings that can mislead and delay the diagnosis. Diagnostic criteria have not been developed yet, whereas several sets of classification criteria are available; however, none of them has 100% sensitivity and 100% specificity, i.e. the hallmark of diagnostic criteria. Nevertheless, classification criteria are often misused as diagnostic criteria, which may affect earliness of diagnosis and lead to more misdiagnosed cases. Areas covered: In this review, we compare old and new classification criteria, discussing their application and pinpointing their limitations in the management of patients. Moreover, we will focus on current and novel biomarkers for SLE diagnosis, highlighting their predictive value and applicability in clinical practice. Expert commentary: SLE diagnosis still represents a challenge, remaining largely based on a clinical judgment. Besides SLE diagnosis, even its classification is still challenging to date. Indeed, although classification of SLE seems to be achieved more frequently with the 2012 SLICC criteria than with the previous 1997 ACR criteria, this last-updated 2012 set might be improved. Notably, diagnostic and classification criteria should be applied to any subject in the world, and consequently they should include immunological variables validated in different populations, which is still an unmet need.


Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Reumatologia , Animais , Biomarcadores/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Valor Preditivo dos Testes , Sensibilidade e Especificidade
16.
Expert Opin Drug Saf ; 14(9): 1373-85, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26212119

RESUMO

INTRODUCTION: Risk of developing cardiovascular disease (CVD) is increased in systemic lupus erythematosus (SLE) compared with the general population. Traditional risk factors cannot account for the totality of CV events and adequate prevention may be challenging. AREAS COVERED: This review summarizes traditional and emerging risk factors of CVD in SLE patients and goes over potential pathogenic mechanisms involved in CVD development. Role of commonly used drugs and preventive strategies exploitable in everyday clinical practice are also discussed. EXPERT OPINION: SLE-related risk factors involve both disease- and treatment-related features, including disease activity, disease phenotype, corticosteroid misuse and alterations of innate and adaptive immunity. Primary prevention is mandatory in management of lupus patients through appropriate disease control, corticosteroid tapering, use of antimalarials and eventually vitamin D supplementation.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Efeitos Psicossociais da Doença , Lúpus Eritematoso Sistêmico/complicações , Imunidade Adaptativa , Animais , Doenças Cardiovasculares/etiologia , Humanos , Imunidade Inata , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Prevenção Primária/métodos , Fatores de Risco
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