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1.
Best Pract Res Clin Rheumatol ; 33(4): 101428, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31810547

RESUMO

The early diagnosis of systemic sclerosis (SSc) can be very difficult, when most of the typical signs and symptoms are absent. For this reason, the approach to SSc has changed during the last decades because the importance of an early diagnosis and treatment has been widely understood. "Very early SSc" is identified as a condition characterized by Raynaud's phenomenon, puffy fingers, disease-specific autoantibodies, and microvascular alterations at capillaroscopy. However, reliable biomarkers able to predict the disease evolution are missing, and decision whether to treat or not to treat in the earliest phase of the disease remains a dilemma. Presently, the only feasible clinical strategy in very early SSc remains a tight follow-up program to detect in "real time" the onset of internal organ involvement, which may thus allow an aggressive therapeutic agenda.


Assuntos
Escleroderma Sistêmico , Autoanticorpos , Diagnóstico Precoce , Humanos , Angioscopia Microscópica , Doença de Raynaud/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico
2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 351-354, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701721

RESUMO

OBJECTIVE: To study the preventive and therapeutic effects of safflower water extract on systemic scleroderma (SSc) in mice and its mechanism. METHODS: Sixty BALB/C mice were randomly divided into the control group, model group, prednisone group and safflower low, middle, high dose groups, 10 mice in each group.The control group was injected with normal saline, and the other five groups were subcutaneously injected with bleomycin hydrochloride with 100 µl at the concentration of 200 µg /ml on the back, once a day for 28 days to establish the SSc models.At the same time, the control group and model group were treated with normal saline (10 ml/kg), the prednisone group was treated with prednisone 4.5 mg/kg (10 ml/kg), and the low, middle, and high dose safflower groups were treated with safflower at the doses of 1.5, 3, 6 g/kg (10 ml/kg), and all groups were treated for 28 days.After 28 days, all mice were decapitated. The blood samples and back skin of the BLM injection part were collected.After that, all the tissue slices were taken to measure the dermal thickness, and the content of hydroxyproline (HYP) in the skin tissues was detected by hydrolysis method.The contents of tissue growth factor (CTGF) and transforming growth factor-ß (TGF-ß ) in the skin tissues and the levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) in serum were determined by ELISA. RESULTS: Compared with the control group, the dermal thickness of the model group was increased(P<0.05), the contents of CTGF, TGF-ß and HYP in the skin tissues and the levels of IL-6 and IL-17 in the serum of the model group were increased(P<0.05); compared with the model group, the dermal thickness in the prednisone group and safflower groups was decreased (P<0.05), the levels of CTGF, TGF-ß and HYP in the skin tissues and the serum levels of IL-6 and IL-17 in the prednisone group and safflower groups were decreased (P<0.05). CONCLUSION: Safflower water extract can improve skin condition (or dermal thickness) in SSc mice, and its mechanism may be related to reducing immune inflammatory response.


Assuntos
Carthamus tinctorius/química , Extratos Vegetais/farmacologia , Escleroderma Sistêmico/tratamento farmacológico , Animais , Bleomicina , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Hidroxiprolina/análise , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo
3.
Medicine (Baltimore) ; 98(38): e17110, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567948

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a clinically complex and challenging disease, the most frequent complication of which is interstitial lung disease, which leads to a worse prognosis. In this situation, cyclophosphamide is considered the criterion standard for treatment, despite the controversies regarding its efficacy and toxicity. However, studies using rituximab (RTX) have shown that this drug may be a promising therapeutic option. The objective is to describe a protocol of a systematic review (SR) that analyzes the scientific evidence on the effects of RTX on SSc. METHODS: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. The databases to be searched are PubMed, Scopus, SciELO, LILACS, ScienceDirect, Web of Science, COCHRANE, WHOLIS, PAHO, and EMBASE. The studies that would be included in SR are clinical trials that evaluate the use of RTX in patients with SSc who meet the classification criteria for the disease according to American College of Rheumatology and European League Against Rheumatism (2013) and/or LeRoy criteria will be included in the SR. The data to be extracted are related to the characteristics of the studies: authors, year of publication, study location, type of study, sample size and age, patient characteristics, duration of intervention, therapeutic scheme, follow-up time, main variables, and main results. RESULTS: In our study, we hope to find articles presenting new evidence supporting treatment of SSc with RTX. CONCLUSIONS: The SR will present results of scientific evidence for the effects of RTX in SSc. We hope that the results could strengthen clinical decisions for the best treatment of SSc and guide future researches. PROSPERO REGISTRATION NUMBER: CRD42019132018.


Assuntos
Antirreumáticos/uso terapêutico , Rituximab/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Antirreumáticos/administração & dosagem , Protocolos Clínicos , Humanos , Rituximab/administração & dosagem , Revisão Sistemática como Assunto
4.
BMC Neurol ; 19(1): 234, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31607267

RESUMO

BACKGROUND: This article reports a case diagnosis of a 44-year-old female who presented with intractable hiccups and vomit complicated with an acute onset of paraplegia. Transverse myelitis was evident on MRI and serological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity. Further studies revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes and their underlying clinical manifestations and therapeutic interventions are seldom reported in literature and are worth reporting. CASE PRESENTATION: The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified on biopsy as steroids-induced scleroderma renal crisis. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where the patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received a written consent forms from the participant in our study, and we have them on file in case they are requested. We have also received the patient's written consent for the data and images presented in this article. CONCLUSION: This article expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.


Assuntos
Mielite Transversa/etiologia , Neuromielite Óptica/complicações , Escleroderma Sistêmico/complicações , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imagem por Ressonância Magnética , Mielite Transversa/tratamento farmacológico , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Rituximab/uso terapêutico , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Síndrome
5.
Autoimmun Rev ; 18(12): 102403, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639515

RESUMO

In systemic sclerosis (SSc), the use of corticosteroids (CS) is controversial due to their association with scleroderma renal crisis (SRC). However, patients with very early and early disease, characterised by main inflammatory component, may benefit from CS therapy. The aim of this review is to discuss pros and cons of CS treatment in SSc, providing current evidence about the use of CS in SSc. Moreover, we discuss also the underlying pathogenetic mechanisms that may be the background for the potential harms and efficacy of CS in SSc.


Assuntos
Corticosteroides/efeitos adversos , Escleroderma Sistêmico/tratamento farmacológico , Humanos , Nefropatias/etiologia , Escleroderma Sistêmico/complicações
6.
Pediatr Rheumatol Online J ; 17(1): 43, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307476

RESUMO

BACKGROUND: We designed and initiated a pilot comparative effectiveness study for juvenile localized scleroderma (jLS), for which there is limited evidence on best therapy. We evaluated the process we used, in relation to the specific protocol and to the general task of identifying strategies for implementing studies in rare pediatric diseases. METHODS: This was a prospective, multi-center, observational cohort study of 50 jLS patients initiating treatment, designed and conducted by the jLS group of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) from 2012 to 2015. A series of virtual and physical meetings were held to design the study, standardize clinical assessments, generate and refine disease activity and damage measures, and monitor the study. Patients were initiated on one of three standardized methotrexate-based treatment regimens (consensus treatment plans, CTPs) and monitored for 1 year. An optional bio-banking sub-study was included. RESULTS: The target enrollment of 50 patients was achieved over 26 months at 10 sites, with patients enrolled into all CTPs. Enrolled patients were typical for jLS. Study eligibility criteria were found to perform well, capturing patients thought appropriate for treatment studies. Minor modifications to the eligibility criteria, primarily to facilitate recruitment for future studies, were discussed with consensus agreement reached on them by the jLS group. There were marked differences in site preferences for specific CTPs, with half the sites treating all their patients with the same CTP. Most patients (88%) completed the study, and 68% participated in the bio-banking substudy. CONCLUSIONS: We demonstrate the feasibility of our approach for conducting comparative effectiveness research in a rare pediatric disease. Multi-center collaboration by dedicated investigators who met regularly was a key factor in the success of this project. Other factors that facilitate these studies include having a sufficient number of investigators to enroll in each regimen, and streamlining study approval and management.


Assuntos
Antirreumáticos/uso terapêutico , Pesquisa Comparativa da Efetividade/métodos , Glucocorticoides/uso terapêutico , Metotrexato/uso terapêutico , Esclerodermia Localizada/tratamento farmacológico , Escleroderma Sistêmico/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adolescente , Criança , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Masculino , Metilprednisolona/uso terapêutico , Projetos Piloto , Prednisona/uso terapêutico , Estudos Prospectivos , Doenças Raras , Adulto Jovem
7.
Reumatismo ; 71(2): 62-67, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31309775

RESUMO

Systemic sclerosis (SSc)-related Raynaud's phenomenon (RP) and digital ulcers (DU) can impair health-related quality of life (HRQoL). The aim of our study was to estimate HRQoL in SSc patients treated with two different intravenous (IV) iloprost (ILO) regimens and in patients not treated with IV ILO. 96 consecutive SSc patients were enrolled in a pragmatic, prospective and non-randomized study, and divided into 3 groups: not requiring therapy with IV ILO (N=52), IV ILO once monthly (N=24) or IV ILO for 5 consecutive days every 3 months (N=20). Patients were followed up for three months. We assessed HRQoL using the generic preference-based questionnaire EQ-5D-5L. We conducted multiple regression analyses to estimate, in each treatment group, the mean general health (GH) and the mean utility index of the EQ-5D-5L, adjusting for possible confounders. The mean adjusted utility index and GH score, after three months' follow-up, were not different in the three groups: IV ILO was able to make patients requiring IV ILO similar to those not requiring it. Moreover, there was no difference in this model between the two ILO regimens (1 day monthly vs 5 consecutive days every 3 months). The two different IV ILO regimens (the most appropriate regimen was decided according to patients' characteristics and needs) were able to stabilize HRQoL in RP secondary to SSc non-adequately controlled by oral therapy.


Assuntos
Iloprosta/administração & dosagem , Qualidade de Vida , Escleroderma Sistêmico/tratamento farmacológico , Administração Intravenosa , Efeitos Psicossociais da Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Inflammopharmacology ; 27(4): 723-730, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069604

RESUMO

Glucocorticoids (GC) are widely used in the treatment of SSc, although there is not much evidence to prove the benefits offered by these drugs in this disease. In this study, we evaluated the effects of a GC on cytokine production in peripheral blood mononuclear cells (PBMC) of SSc patients. The effect of dexamethasone (DEX) was evaluated in PBMC of 21 SSc patients and 10 healthy volunteers after stimulation of cells with anti-CD3 and anti-CD28. Cytokines IL-2, IL-4, IL-6, IL-10, IL-17A, IL-17F, IFN-γ, TNF, and IL-1ß were quantified in the culture supernatant by CBA or ELISA. Of the patients evaluated in this study, 8 (38%) were taking corticosteroids, and esophageal dysfunction was more frequent in these patients when compared to those who did not take corticosteroids. DEX (1.000 nM) treatment in PBMC of SSc patients stimulated with anti-CD3 and anti-CD28 promoted a significant reduction in IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IL-1ß (p < 0.001 for all), and IL-17F (p = 0.023) cytokines levels. We did not observe differences in response to in vitro treatment with DEX between groups of patients taking or not taking corticosteroids. In PBMC from healthy volunteers, we observed that DEX treatment significantly reduced IL-4, IFN-γ (p = 0.003 for both), IL-6, IL-10, IL-17A, and TNF (p = 0.002 for all) cytokines. These results show that DEX treatment in PBMC of SSc patients reduced the production of important cytokines involved in the pathogenesis of the disease, suggesting a possible mechanism of action of the CG in the treatment of SSc.


Assuntos
Citocinas/metabolismo , Dexametasona/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Escleroderma Sistêmico/tratamento farmacológico , Corticosteroides/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/metabolismo , Adulto Jovem
10.
J Med Case Rep ; 13(1): 145, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31084620

RESUMO

BACKGROUND: Scleredema is a rare sclerodermoid skin condition characterized by diffuse symmetrical thickening of the upper part of the body. Its association with monoclonal gammopathy and myeloma was recently described; very few cases have been reported to date. CASE PRESENTATION: A 66-year-old Sri Lankan woman who had been followed in a dermatology unit for 34 years with diffuse systemic sclerosis presented with an acute exacerbation of the skin disease. Absence of Raynaud's phenomenon; sclerodactyly; characteristic lung, gastrointestinal, and cardiac involvement of systemic sclerosis; and repeatedly negative antinuclear antibodies test results led to reevaluation for the possibility of scleredema. Skin biopsies from four body sites showed normal epidermis and thickened reticular dermis with swollen collagen bundles separated from one another by clear spaces, resulting in fenestration. The skin appendages were not atrophied or bound down. Alcian blue staining showed interstitial mucin deposition. Serum protein electrophoresis demonstrated an abnormal monoclonal band in the ß-region with a paraprotein level of 8.9 g/dl. Immunofixation showed an abnormal band in the γ-region consisting of immunoglobulin A and κ. Bone marrow biopsy revealed abnormal monoclonal plasma cells (15%) with multinuclearity. There was no evidence of end organ damage, and whole-body magnetic resonance imaging did not reveal any evidence of bone involvement. The patient's diagnosis was revised as scleredema type 2 associated with IgA-κ, and she was referred to a hemato-oncologist for chemotherapy, which led to significant improvement in the skin condition. CONCLUSIONS: Scleredema is a rare disorder that has an enigmatic, rare association with monoclonal gammopathy. Dermatologists should be aware of this rare but important association.


Assuntos
Imagem por Ressonância Magnética , Escleredema do Adulto/diagnóstico por imagem , Escleroderma Sistêmico/fisiopatologia , Mieloma Múltiplo Latente/diagnóstico por imagem , Imagem Corporal Total , Idoso , Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Progressão da Doença , Feminino , Humanos , Imunoglobulinas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Escleredema do Adulto/tratamento farmacológico , Escleredema do Adulto/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Mieloma Múltiplo Latente/tratamento farmacológico , Mieloma Múltiplo Latente/fisiopatologia , Resultado do Tratamento
11.
Z Rheumatol ; 78(5): 439-457, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31089800

RESUMO

Systemic sclerosis is a rare rheumatologic disease that is characterised by skin and organ fibrosis as well as vascular changes and the occurrence of specific autoantibodies. It has a high morbidity and mortality while its manifestations show significant heterogeneity in patients. Thus, diagnosis and follow-up of patients with systemic sclerosis has to be extensive, the more so because treatment must adapted to organ manifestations. Although specific therapies for gastrointestinal, pulmonary or vascular complications exist, patients respond only partly to these and new therapeutic approaches are still needed.


Assuntos
Escleroderma Sistêmico , Autoanticorpos , Fibrose , Humanos , Imunossupressores/uso terapêutico , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/imunologia , Pele
12.
Arthritis Rheumatol ; 71(11): 1812-1823, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31131994

RESUMO

OBJECTIVE: To evaluate predictors of serious infection events (SIEs) during rituximab (RTX) therapy and effects of hypogammaglobulinemia on SIE rates, and humoral response and its persistence after discontinuation of RTX in the treatment of rheumatic and musculoskeletal diseases (RMDs). METHODS: A retrospective longitudinal study of 700 RMD patients treated with RTX in a single center was conducted. Immunoglobulin levels were measured at baseline and at 4-6 months after each treatment cycle. Baseline predictors of SIEs were assessed using multivariable logistic regression; for RTX cycles 2-4, a mixed-effects logistic regression model was used. RESULTS: A total of 507 patients (72%) had rheumatoid arthritis, 94 (13%) had systemic lupus erythematosus, 49 (7%) had antineutrophil cytoplasmic antibody-associated vasculitis, and 50 (7%) had other RMDs. The number of SIEs recorded was 281 in 176 patients (9.8 per 100 person-years). Predictors of SIEs included non-RTX-specific comorbidities (previous history of SIE, cancer, chronic lung disease, diabetes mellitus, and heart failure), higher corticosteroid dose, and RTX-specific factors, including low IgG (<6 gm/liter) both at baseline and during treatment, RTX-associated neutropenia, higher IgM, and longer time to RTX re-treatment, but not B cell count or depletion status. Of 110 patients with low IgG, SIE rates were higher in those with low IgG at baseline (16.4 per 100 person-years) and in those who acquired low IgG during or after RTX treatment (21.3 per 100 person-years) versus those with normal IgG (9.7 per 100 person-years). Five of 8 patients (63%) had impaired humoral response to pneumococcus and hemophilus following vaccination challenge, and only 4 of 11 patients (36%) had IgG normalized after switching biologic disease-modifying antirheumatic drugs. CONCLUSION: Immunoglobulin levels should be monitored at baseline and before each RTX cycle to identify patients at risk of SIEs. Individualized risk-benefit assessment should be undertaken in those with lower IgG as this is a consistent SIE predictor and may increase infection profiles when RTX is switched to different therapies.


Assuntos
Agamaglobulinemia/induzido quimicamente , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Rituximab/efeitos adversos , Adulto , Agamaglobulinemia/imunologia , Idoso , Comorbidade , Doenças do Tecido Conjuntivo/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Feminino , Glucocorticoides/administração & dosagem , Insuficiência Cardíaca/epidemiologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Estudos Longitudinais , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Neoplasias/epidemiologia , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Estudos Retrospectivos , Doenças Reumáticas/tratamento farmacológico , Medição de Risco , Fatores de Risco , Escleroderma Sistêmico/tratamento farmacológico , Índice de Gravidade de Doença , Síndrome de Sjogren/tratamento farmacológico , Fatores de Tempo
13.
N Engl J Med ; 380(26): 2518-2528, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31112379

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was -52.4 ml per year in the nintedanib group and -93.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P = 0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of -0.21 (95% CI, -0.94 to 0.53; P = 0.58) and 1.69 (95% CI, -0.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo. (Funded by Boehringer Ingelheim; SENSCIS ClinicalTrials.gov number, NCT02597933.).


Assuntos
Inibidores Enzimáticos/uso terapêutico , Indóis/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Escleroderma Sistêmico/complicações , Administração Oral , Adulto , Diarreia/induzido quimicamente , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Indóis/efeitos adversos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/tratamento farmacológico , Capacidade Vital
14.
Eur J Clin Invest ; 49(7): e13123, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077590

RESUMO

BACKGROUND: After the Q fever outbreak in the Netherlands between 2007 and 2010, more than 300 patients with chronic Q fever have been identified. Some patients were also diagnosed with systemic sclerosis, a rare immune-mediated disease. We aimed to increase awareness of concomitant chronic Q fever infection and systemic sclerosis and to give insight into the course of systemic sclerosis during persistent Q fever infection. MATERIALS AND METHODS: Chronic Q fever patients were identified after the Dutch Q fever outbreak in 2007-2010. Systemic sclerosis was diagnosed by a scleroderma expert and patients fulfilled the 2013 Classification Criteria for Systemic Sclerosis. RESULTS: Four cases presented with chronic Q fever, persistent Coxiella burnetii infection, shortly preceded or followed by the diagnosis of limited cutaneous systemic sclerosis. The three male patients of 60 years or older developed a relatively mild systemic sclerosis, which did not require immunosuppressive therapy during adequate treatment of the chronic Q fever infection. The 58-year-old female patient used immunosuppressives for her newly diagnosed systemic sclerosis at the time she likely developed a chronic Q fever infection. CONCLUSIONS: In this case series, chronic Q fever preceding systemic sclerosis was associated with a mild course of systemic sclerosis without the necessity of immunosuppressive drugs, while chronic Q fever development due to immunocompromised state was associated with a more deteriorating course of systemic sclerosis.


Assuntos
Febre Q/complicações , Escleroderma Sistêmico/complicações , Idoso , Anticorpos Antibacterianos/metabolismo , Doença Crônica , Coxiella burnetii/imunologia , Feminino , Humanos , Imunoglobulina G/metabolismo , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/tratamento farmacológico
15.
Int J Rheum Dis ; 22(6): 1041-1045, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30938067

RESUMO

AIM: Low levels of vitamin D (25OHD) have been found to associated with digital ulcers (DUs) in systemic sclerosis (SSc), although only cross-sectional studies have been performed. We aimed to investigate if variations in vitamin D serum levels over time affect DU in SSc. METHODS: This is a retrospective study on 65 patients. 25OHD was measured in 2011 and 2016 and its variations correlated with DU. RESULTS: The mean age of our cohort was 58 (SD 12) years with a mean disease duration of 9.5 (5.3) years. Most of our patients had a limited SSc (69.2%). At baseline 50.8% and 41.5% after 5 years had 25OHD <30 ng/mL. Patients receiving supplementation (8750 IU/wk) at baseline numbered 39 (60.0%) and 45 (69.2%) at the end of follow up. Nevertheless, 31 (47.7%) had a decrease of 25OHD in 5 years. In univariate analysis, patients with incident DU had a decrease in 25OHD as compared to patients with no incident DU (-17.4 [37.0] vs 13.0 [89.5], P = 0.018). No differences in 25OHD variations were found for other disease characteristics. In multivariate analysis correcting for previous DU and modified Rodnan Skin Score at baseline, patients with a decrease in 25OHD had an increased risk of developing DU (odds ratio 16.6; 95% CI 1.7-164.5, P = 0.017). CONCLUSIONS: A decrease in 25OHD is associated with the risk of developing DUs. In addition, vitamin D supplementation with the doses currently recommended may be insufficient in SSc. Further studies in wider cohorts are needed to confirm these results.


Assuntos
Escleroderma Sistêmico/sangue , Úlcera Cutânea/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Idoso , Biomarcadores/sangue , Suplementos Nutricionais , Feminino , Humanos , Incidência , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/epidemiologia , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/epidemiologia , Úlcera Cutânea/prevenção & controle , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia
16.
J Dermatol Sci ; 94(1): 205-212, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30954335

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although transforming growth factor (TGF)-ß1-induced connective tissue growth factor (CTGF/CCN2) expression has been presented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully explored. COA-Cl is a novel nucleic acid analog, which is reported to have pleiotropic beneficial biologic effects. OBJECTIVE: We examine the effects of COA-Cl on TGF-ß1-induced CTGF expression in normal human dermal fibroblast (NHDF). We also examined the effects of COA-Cl on CTGF expression in a mouse SSc model of angiotensin II (Ang II)-induced skin fibrosis. METHODS: NHDF was cultured for in vitro experiments. For in vivo experiments, C57BL/6J mice were treated with Ang II for 14 days by subcutaneous osmotic pump. Quantitative real-time polymerase chain reaction, western blot analysis, immunohistochemical staining and immunofluorescence staining were performed to examine the expression levels of CTGF and phosphorylation levels of Smad2/3, ERK1/2 and Akt. RESULTS: COA-Cl attenuated the TGF-ß1-induced expression of both CTGF mRNA and protein in NHDF. Although COA-Cl did not alter the TGF-ß1-induced phosphorylation of Smad2/3 or ERK1/2, it reduced the TGF-ß1-induced phosphorylation levels of Akt in NHDF. Notably, COA-Cl dephosphorylated the Akt of lysates of TGF-ß1-treated NHDF. COA-Cl reduced the levels of CTGF mRNA, CTGF protein, dermal thickness, collagen content and Akt phosphorylation in the skin of mice SSc model. CONCLUSION: These results imply that the inhibition of TGF-ß1-induced CTGF expression by COA-Cl may be a therapeutic approach for SSc.


Assuntos
Adenosina/análogos & derivados , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Escleroderma Sistêmico/tratamento farmacológico , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo , Adenosina/farmacologia , Adenosina/uso terapêutico , Angiotensina II/toxicidade , Animais , Linhagem Celular , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose/tratamento farmacológico , Fibrose/etiologia , Fibrose/patologia , Humanos , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Escleroderma Sistêmico/patologia , Pele/efeitos dos fármacos
18.
Clin Exp Med ; 19(3): 357-366, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30989453

RESUMO

Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud's phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of patients' life. The management of vascular disease can be challenging for the clinician because of the suboptimal tolerability of the treatments and lack of consensus on the best therapeutic approach. Intravenous iloprost, a synthetic analogue of prostacyclin, is broadly used for the treatment of RP and ischemic ulcers secondary to SSc. However, no standardized protocol on iloprost use is currently available and, consequently, the management of this treatment is largely based on the experience of each single center. The PROSIT project is an observational, multicenter study aiming to investigate the current treatments for SSc vasculopathy, the use of prostanoids, with special regard to iloprost, and the perception of the treatment from a patient's perspective. The study was conducted on a cohort of 346 patients from eight Italian centers and included a structured survey addressed to physicians, data collected from patient's medical records and two patient-administered questionnaires assessing the level of satisfaction, tolerability and perception of the efficacy of Iloprost. PROSIT data confirmed that in the contest of SSc iloprost represents the first-line choice for the management of severe RP and DU. Moreover, it is a well-tolerated treatment as reported by patients' experience. Although a standard protocol for the treatment of SSc-related vasculopathy is lacking, PROSIT study identified different therapeutic approaches largely supported by tertiary Italian centers. Further studies are needed in order to optimize the best treatment for SSc vascular diseases, in particular to improve the best iloprost schedule management.


Assuntos
Gerenciamento Clínico , Iloprosta/uso terapêutico , Doenças Vasculares Periféricas/tratamento farmacológico , Doenças Vasculares Periféricas/patologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Vasodilatadores/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
19.
Colloids Surf B Biointerfaces ; 179: 453-461, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31005740

RESUMO

We developed a facile fabrication method for preparing poly(ethylene glycol)(PEG)-coated poly (lactic-co-glycolic acid) (PLGA) microspheres with homogeneous size distribution via a combination of mPEG-b-PLGA and Shirasu Porous Glass membrane emulsification. Subsequently, extracellular matrix (ECM) degrading enzymes, collagenase (COLase) or hyaluronidase (HAse) were loaded into the microspheres. The obtained microspheres exhibited a sustained release of COLase or HAse over 10 days. The degradation of ECM polymers by the released COLase and HAse was confirmed in vitro. Reversal of established dermal fibrosis via degradation of over-deposited ECM is a promising treatment for scleroderma. The therapeutic effects of COLase- and HAse-loaded PLGA microspheres on scleroderma were evaluated in vivo following their intradermal administration to a bleomycin-induced mice model of scleroderma. COLase- and HAse-loaded PLGA microspheres decreased scleroderma dermal thickness without altering the mechanical properties of skin, whereas the administration of free COLase and HAse solution induced overdecomposition of skin ECM and α-SMA expression. The facile one-pot synthesis of PEG-coated PLGA microspheres with high colloidal stability and narrow size distribution could be employed as a drug carrier for various diseases in future.


Assuntos
Colagenases/uso terapêutico , Vidro/química , Hialuronoglucosaminidase/uso terapêutico , Membranas Artificiais , Microesferas , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Escleroderma Sistêmico/tratamento farmacológico , Animais , Bovinos , Coloides/química , Modelos Animais de Doenças , Emulsões/química , Matriz Extracelular/metabolismo , Ferro/metabolismo , Camundongos , Tamanho da Partícula , Porosidade , Pele/metabolismo , Pele/patologia , Suínos
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