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2.
J Clin Pathol ; 71(7): 620-625, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29447111

RESUMO

AIM: Humoral immunity and B cells are thought to play an important role in the pathophysiology of the systemic sclerosis (SSc). The production of free light chains (FLC) of immunoglobulins is abnormally high in several pathological autoimmune conditions and reflects B cell activation. Furthermore, FLCs demonstrated different biological activities including their capability to modulate the immune system, proteolytic activity and complement cascade activation. The aims of this study are to determine the FLC levels in patients with SSc compared with healthy controls (HC) and to study their possible association with organ involvement and disease characteristics. METHODS: Sixty-five patients with SSc and 20 HC were studied. Clinical and immunological inflammatory characteristics were assessed for all the patients with SSc. κ-FLC and λ-FLC, interleukin 6 (IL-6) and B cell activating factor levels were measured. RESULTS: The mean serum κ-FLC levels and FLC ratio were significantly higher in patients with SSc compared with HC, while the serum λ-FLC levels were comparable.The levels of FLC were comparable in patients with diffuse skin disease and limited skin involvement, while κ-FLC levels were increased in patients with restrictive lung (forced vital capacity (FVC) <80%) disease (26.4±7.4 mg/L) when compared with patients with FVC ≥80% (19.6±7.3 mg/L, P=0.009). In patients with SSc, the levels of serum κ-FLC level directly correlated with the IL-6 levels (R=0.3, P=0.001) and disease activity (R=0.4, P=0.003). CONCLUSIONS: FLC levels are elevated in SSc and high levels are associated with lung involvement and with a higher degree of inflammation, supporting a possible role of B cell activation in the pathophysiology of the disease.


Assuntos
Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Inflamação/sangue , Pulmão/imunologia , Esclerodermia Difusa/sangue , Esclerodermia Limitada/sangue , Adulto , Idoso , Fator Ativador de Células B/sangue , Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Humanos , Cadeias kappa de Imunoglobulina/imunologia , Cadeias lambda de Imunoglobulina/imunologia , Inflamação/diagnóstico , Inflamação/imunologia , Interleucina-6/sangue , Interleucina-6/imunologia , Pulmão/fisiopatologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/imunologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/imunologia , Esclerodermia Limitada/fisiopatologia , Regulação para Cima , Capacidade Vital
3.
Rheumatol Int ; 38(3): 363-374, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29322341

RESUMO

OBJECTIVES: To evaluate the clinical characteristics of patients with interstitial lung disease (ILD) in the setting of a large cohort of systemic sclerosis (SSc) patients, and to analyse the differences according to the SSc subtype (following the modification of classification criteria of the American College of Rheumatology for SSc proposed by LeRoy and Medsger), factors are associated with moderate-to-severe impairment of lung function, as well as mortality and causes of death. METHODS: A descriptive study was performed, using the available data from the Spanish Scleroderma Study Group. RESULTS: Twenty-one referral centers participated in the registry. By April 2014, 1374 patients with SSc had been enrolled, and 595 of whom (43%) had ILD: 316 (53%) with limited cutaneous SSc (lcSSc), 240 (40%) with diffuse cutaneous SSc (dcSSc), and 39 (7%) with SSc sine scleroderma (ssSSc). ILD in the lcSSc and the ssSSc subsets tended to develop later, and showed a less impaired forced vital capacity (FVC) and a ground glass pattern on high-resolution computed tomography (HRCT) less frequently, compared with the dcSSc subset. Factors related to an FVC < 70% of predicted in the multivariate analysis were: dcSSc, positivity to anti-topoisomerase I antibodies, a ground glass pattern on HCRT, an active nailfold capillaroscopy pattern, lower DLco, older age at symptoms onset, and longer time between symptoms onset and ILD diagnosis. Finally, SSc-associated mortality and ILD-related mortality were highest in dcSSc patients, whereas that related to pulmonary arterial hypertension was highest in those with lcSSc-associated ILD. CONCLUSIONS: Our study indicates that ILD constitutes a remarkable complication of SSc with significant morbidity and mortality, which should be borne in mind in all three subgroups (lcSSc, dcSSc, and ssSSc).


Assuntos
Doenças Pulmonares Intersticiais , Pulmão , Esclerodermia Difusa , Esclerodermia Limitada , Adulto , Idoso , Causas de Morte , Distribuição de Qui-Quadrado , Feminino , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Modelos Logísticos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/mortalidade , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/terapia , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Prognóstico , Sistema de Registros , Fatores de Risco , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/mortalidade , Esclerodermia Difusa/fisiopatologia , Esclerodermia Difusa/terapia , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/mortalidade , Esclerodermia Limitada/fisiopatologia , Esclerodermia Limitada/terapia , Índice de Gravidade de Doença , Pele/patologia , Espanha/epidemiologia , Tomografia Computadorizada por Raios X , Capacidade Vital
4.
Microvasc Res ; 114: 41-45, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28602918

RESUMO

BACKGROUND: The angiogenesis in systemic sclerosis (SSc) is impaired. An imbalance of pro-angiogenic factors and angiogenesis inhibitors has been implicated in the progression of peripheral microvascular damage, defective vascular repair and fibrosis. Intrarenal resistance index are considered markers of renal vasculopathy. The aim of the study is to evaluate angiogenic and angiostatic factors (VEGF and endostatin) in SSc patients and to correlate with intrarenal hemodynamic parameters. METHODS: 91 SSc patients were enrolled in this study. Serum VEGF and endostatin levels were determined. All patients underwent a renal Doppler ultrasound RESULTS: A significant positive correlation was observed between endostatin and renal Doppler parameters (p<0.0001). A negative correlation was observed between serum levels of endostatin and eGFR (p<0.01). In SSc patients with high resistive index, serum levels of endostatin were significantly (p<0.01) higher than in SSc patients with normal resistive index. The serum levels of endostatin significantly increased with progression of nailfold videocapillaroscopy damage (p<0.01) and were significantly (p<0.05) higher in SSc patients with digital ulcers than in SSc patients without digital ulcers. CONCLUSION: This is the first study that assess in SSc patients intrarenal hemodynamic parameters and endostatin. In SSc patients, endostatin represents a marker of renal scleroderma-associated vasculopathy.


Assuntos
Endostatinas/sangue , Hemodinâmica , Nefropatias/sangue , Rim/irrigação sanguínea , Circulação Renal , Esclerodermia Difusa/sangue , Esclerodermia Limitada/sangue , Doenças Vasculares/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Neovascularização Patológica , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/fisiopatologia , Ultrassonografia Doppler , Doenças Vasculares/diagnóstico , Doenças Vasculares/fisiopatologia
5.
Acta Orthop Traumatol Turc ; 51(1): 88-90, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28017514
6.
Rheumatology (Oxford) ; 56(1): 87-94, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28028158

RESUMO

OBJECTIVES: Pulmonary hypertension (PH) is an important cause of morbidity and mortality in patients with SSc. The submaximal heart and pulmonary evaluation (step test) is a non-invasive, submaximal stress test that could be used to identify SSc patients with PH. Our aims were to determine whether change in end tidal carbon dioxide ([Formula: see text]) from rest to end-exercise, and the minute ventilation to carbon dioxide production ratio ([Formula: see text]), both as measured by the step test, differ between SSc patients with and without PH. We also examined differences in validated self-report questionnaires and potential PH biomarkers between SSc patients with and without PH. METHODS: We performed a cross-sectional study of 27 patients with limited or dcSSc who underwent a right heart catheterization within 24 months prior to study entry. The study visit consisted of questionnaire completion; history; physical examination; step test performance; and phlebotomy. [Formula: see text], [Formula: see text], self-report data and biomarkers were compared between patients with and without PH. RESULTS: SSc patients with PH had a statistically significantly lower median (interquartile range) [Formula: see text] than SSc patients without PH [-2.1 (-5.1 to 0.7) vs 1.2 (-0.7 to 5.4) mmHg, P = 0.035], and a statistically significantly higher median (interquartile range) [Formula: see text] [53.4 (39-64.1) vs 36.4 (31.9-41.1), P = 0.035]. There were no statistically significant differences in self-report data or biomarkers between groups. CONCLUSION: [Formula: see text] and [Formula: see text] as measured by the step test are statistically significantly different between SSc patients with and without PH. [Formula: see text] and [Formula: see text] may be useful screening tools for PH in the SSc population.


Assuntos
Dióxido de Carbono/metabolismo , Hipertensão Pulmonar/metabolismo , Pulmão/metabolismo , Esclerodermia Difusa/metabolismo , Esclerodermia Limitada/metabolismo , Idoso , Testes Respiratórios , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Interleucina-6/metabolismo , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Troca Gasosa Pulmonar , Ventilação Pulmonar , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esclerodermia Difusa/complicações , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/complicações , Esclerodermia Limitada/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Arthritis Care Res (Hoboken) ; 68(10): 1554-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26867144

RESUMO

OBJECTIVE: Anticentromere antibodies (ACAs) define a subset of primary Sjögren's syndrome (SS) with a unique phenotype, including features of limited cutaneous systemic sclerosis and a lower frequency of anti-SSA/SSB antibodies. We sought to determine whether ACAs are associated with more severe exocrine glandular dysfunction in a large cohort of primary SS subjects. METHODS: We performed a cross-sectional analysis of 1,361 subjects with primary SS from the Sjögren's International Collaborative Clinical Alliance Registry, stratified by the presence or absence of ACAs. ACAs were assayed by immunofluorescence staining on HEp-2 cells. RESULTS: ACAs were present in 82 of the 1,361 SS subjects (6%) and were associated with older age, female sex, and lower frequencies of anti-SSA/SSB, rheumatoid factor, and hyperglobulinemia. Among ACA-positive versus ACA-negative subjects, there was a higher frequency of a focus score ≥2 (71% versus 53%; P = 0.002), a higher median focus score (2.8 versus 2.5; P = 0.0440), and greater exocrine gland dysfunction: Schirmer's test value: median 4 versus 5 mm/5 minutes; P = 0.0003, and unstimulated whole saliva (UWS) flow rate: median 0.08 versus 0.37 ml/5 minutes; P < 0.0001. ACA-positive subjects had an increased risk of UWS <0.1 ml/minute (odds ratio [OR] 12.24 [95% confidence interval (95% CI) 4.91-41.02]) and Schirmer's test value <5 mm/5 minutes (OR 2.52 [95% CI 1.50-4.36]) after correcting for age, sex, anti-SSA/SSB, and focus score. Labial gland fibrosis was not different between the 2 groups. CONCLUSION: In a large international registry of SS, ACA had an independent association with more severe exocrine glandular dysfunction. This dysfunction was associated with more pronounced labial salivary glandular inflammation but not fibrosis.


Assuntos
Anticorpos Antinucleares/sangue , Glândulas Exócrinas/fisiopatologia , Esclerodermia Limitada/imunologia , Síndrome de Sjogren/imunologia , Estudos Transversais , Glândulas Exócrinas/imunologia , Feminino , Humanos , Hipergamaglobulinemia/imunologia , Hipergamaglobulinemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Sistema de Registros , Fator Reumatoide/sangue , Saliva/fisiologia , Glândulas Salivares/imunologia , Glândulas Salivares/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Índice de Gravidade de Doença , Sialadenite/imunologia , Sialadenite/fisiopatologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/fisiopatologia
8.
Microvasc Res ; 105: 119-24, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26907637

RESUMO

OBJECTIVES: To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients. METHODS: Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated. RESULTS: SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (p<0.0001), but not at the level of face and dorsum of hands. A gradual decrease of BP at fingertips, periungual and palm areas, was found in SSc patients with progressive severity of NVC patterns of microangiopathy ("early", "active", or "late") (p<0.01). A negative correlation was observed between MES and BP values, as well as between loss of capillaries and BP, at the same areas (p<0.001 and p<0.01, respectively). Patients with diffuse cutaneous SSc (dcSSc) showed lower BP than those with limited cutaneous SSc (p<0.04). CONCLUSIONS: LASCA detects a significant reduction of BP only in those areas usually affected by Raynaud's phenomenon (fingertips, periungual and palm areas), especially in dcSSc patients, and BP values significantly correlate with the nailfold capillaroscopy scores of microangiopathy.


Assuntos
Fluxometria por Laser-Doppler , Angioscopia Microscópica , Unhas/irrigação sanguínea , Imagem de Perfusão/métodos , Esclerodermia Difusa/diagnóstico , Esclerodermia Limitada/diagnóstico , Pele/irrigação sanguínea , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Índice de Gravidade de Doença
9.
Eye (Lond) ; 30(4): 588-92, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26795407

RESUMO

PURPOSE: To investigate the choroidal thickness in patients with scleroderma and to compare them with healthy control subjects. METHODS: Forty-six patients with scleroderma (3 male and 43 female) and 31 healthy controls (6 male and 25 female) were included in the study. Twenty-five patients had limited-type and 21 patients had diffuse-type scleroderma. Only left eyes of the patients and control subjects were used in the analysis. Demographic features of all the patients and control subjects were recorded. Each subject underwent ophthalmological examinations including refraction, visual acuity, intraocular pressure, axial length (AXL) measurement, slit-lamp biomicroscopy, and fundus examination. Body mass index (BMI) was estimated for all participants. RESULTS: There were no significant differences between the patients with scleroderma and the control subjects in terms of age, gender, BMI, mean AXL, and mean spherical equivalent refractive error (SE) (P=0.1, P=0.086, P=0.37, P=0.55, and P=0.072 respectively). The patients with scleroderma had significantly thinner nasal, temporal, and subfoveal choroid than the healthy control subjects (P1=0.012, P2=0.046, and P3<0.001, respectively). There were no significant differences between the patients with limited-type and diffuse-type scleroderma in terms of age, gender, BMI, mean AXL, mean SE, nasal, temporal, and subfoveal choroidal thicknesses (all P>0.05). CONCLUSIONS: Choroidal thickness in patients with scleroderma was significantly less than healthy control subjects. Vasculopathy in scleroderma is characterized by obliteration of arterioles and reduced capillary density may cause atrophy of choroid in patients with scleroderma.


Assuntos
Corioide/patologia , Esclerodermia Difusa/complicações , Esclerodermia Limitada/complicações , Adulto , Índice de Massa Corporal , Feminino , Voluntários Saudáveis , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Refração Ocular/fisiologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
10.
Int J Dermatol ; 55(8): 882-5, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26499848

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a multiorgan autoimmune disorder characterized by sclerosis of the skin and organs as well as the presence of antinuclear autoantibodies. Several types of antinuclear autoantibodies have been described in SSc, associated with distinct disease entities and differences in prognosis. METHODS: The aim of this study was to screen for the presence of antibodies reacting with RNA polymerase III (anti-RNAP3) in a large cohort of patients with SSc treated at a tertiary referral center and to evaluate correlations with disease severity. RESULTS: Anti-RNAP3 antibodies were detected in 11 of 158 patients (7.0%). Eight of the 11 (72.7%) anti-RNAP3-positive patients had diffuse cutaneous SSc (P < 0.01). A higher modified Rodnan skin score, associated with diffuse SSc, correlated with the presence of anti-RNAP3 (P < 0.0001). The detection of anti-RNAP3 antibodies strongly correlated with the presence of renal involvement (P < 0.0001). The odds ratio of RNAP3-positive patients to develop renal involvement was 80.1 (95% CI 9.3-690.1). CONCLUSIONS: This study demonstrates that the detection of anti-RNAP3 antibodies in patients with SSc correlates with renal crisis and severe cutaneous involvement. The possibility to detect specific antibodies with a prognostic value can lead to a better risk management of patients with SSc.


Assuntos
Autoanticorpos/imunologia , Biomarcadores/metabolismo , Nefropatias/fisiopatologia , RNA Polimerase III/análise , Escleroderma Sistêmico/imunologia , Dermatopatias/fisiopatologia , Adulto , Idoso , Autoanticorpos/análise , Distribuição de Qui-Quadrado , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Alemanha , Humanos , Nefropatias/epidemiologia , Nefropatias/imunologia , Masculino , Pessoa de Meia-Idade , RNA Polimerase III/imunologia , Estudos Retrospectivos , Medição de Risco , Esclerodermia Difusa/epidemiologia , Esclerodermia Difusa/imunologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/epidemiologia , Esclerodermia Limitada/imunologia , Esclerodermia Limitada/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Dermatopatias/epidemiologia , Dermatopatias/imunologia
11.
Clin Exp Rheumatol ; 33(4 Suppl 91): S123-6, 2015 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26242276

RESUMO

OBJECTIVES: A key mediator in cold-sensation is the protein transient receptor potential melastatin 8 (TRPM8), which is expressed on sensory nerves and cutaneous blood vessels. These receptors are activated by cold temperatures and play a key role in body thermoregulation. Cold sensitivity and Raynaud's phenomenon are frequent clinical features in scleroderma, and are thought to be secondary to a local defect in cutaneous thermoregulation. We investigated whether autoantibodies targeting TRPM8 were present in the sera of patients with scleroderma as evidence for a possible mechanism for an acquired immune mediated defect in thermoregulation. METHODS: Sera from 50 well-characterised scleroderma patients with Raynaud's phenomenon were studied. TRPM8 autoantibodies were assayed as follows: 1. immunoprecipitation with 35S-methionine-labelled TRPM8 generated by in vitro transcription and translation, 2. immunoblotting lysates made from cells transiently transfected with TRPM8 cDNA, 3. Immunoprecipitation of TRPM8 transfected lysates with detection by blotting and 4. flow cytometry. RESULTS: Fifty scleroderma patients with Raynaud's phenomenon (41 female, 39 Caucasian, 23 with limited scleroderma, and 20 with history of cancer) were studied. Four different methods to assay for TRPM8 antibodies were set up, optimised and validated using commercial antibodies. All 50 scleroderma patients' sera were assayed using each of the above methods, and all were negative for TRPM8 autoantibodies. CONCLUSIONS: Antibodies against TRPM8 are not found in scleroderma patient sera, suggesting that the abnormal cold sensitivity and associated abnormal vascular reactivity in scleroderma patients is not the result of an immune process targeting TRPM8.


Assuntos
Autoanticorpos/sangue , Doença de Raynaud/imunologia , Esclerodermia Difusa/imunologia , Esclerodermia Limitada/imunologia , Canais de Cátion TRPM/imunologia , Adulto , Idoso , Biomarcadores/sangue , Regulação da Temperatura Corporal , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Doença de Raynaud/sangue , Doença de Raynaud/diagnóstico , Doença de Raynaud/fisiopatologia , Esclerodermia Difusa/sangue , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/sangue , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/fisiopatologia , Testes Sorológicos , Sensação Térmica
12.
Ann Rheum Dis ; 74(4): 730-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24389298

RESUMO

BACKGROUND: Systemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status. OBJECTIVES: To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc). METHODS: The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed. RESULTS: Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often 'other antibodies' (68.0%; p<0.0001), including anti-U1RNP, -PmScl, -Ro, -La, as well as anti-Jo-1 and -Ku antibodies. These patients developed musculoskeletal involvement earlier and more frequently (62.5%) than patients diagnosed as lcSSc (32.2%) or dcSSc (43.3%) (p<0.0001). The onset of lung fibrosis and heart involvement in SSc-overlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset. CONCLUSIONS: These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement.


Assuntos
Doenças do Tecido Conjuntivo/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Adulto , Autoanticorpos/imunologia , Cardiomiopatias/etiologia , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/imunologia , Bases de Dados Factuais , Progressão da Doença , Feminino , Gastroenteropatias/etiologia , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fibrose Pulmonar/etiologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/imunologia , Síndrome
13.
Clin Exp Rheumatol ; 32(6 Suppl 86): S-88-93, 2014 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25372793

RESUMO

OBJECTIVES: Knowledge about the nature and impact of symptoms faced by patients with systemic sclerosis (SSc) is needed to identify targets for research and treatment. The aim of this study was to assess and compare the frequency and impact on everyday activities of SSc symptoms among patients from five European countries. METHODS: European patients with SSc were invited through announcements by patient associations to complete an online survey. The survey included items assessing the frequency of 40 SSc symptoms and the impact on daily activities, if present. Chi-square tests were utilised to assess the differences in frequency and impact of symptoms across countries. RESULTS: In total, 537 patients were included from France (n=111), the Netherlands (n=229), Spain (n=61), Switzerland (n=50), and the United Kingdom (n=86). Symptoms experienced by ≥ 70% of patients in all countries were fatigue, Raynaud's phenomenon, joint pain, and muscle pain. Twenty symptoms were experienced by ≥ 50% of patients in all countries. Thirty symptoms had an impact on daily activities in ≥ 50% of patients who reported that the symptom was present in all countries. There were significant differences among countries in the prevalence of 17 out of 40 symptoms. Furthermore, in 24 out of 40 symptoms significant differences in the proportion of patients reporting impact of a specific symptom on everyday activities were observed. CONCLUSIONS: European patients with SSc experience a broad range of symptoms that have an impact on everyday activities. International research initiatives should target common SSc symptoms cooperatively. Further research is needed to better understand the differences in SSc symptoms among countries.


Assuntos
Atividades Cotidianas , Limitação da Mobilidade , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Idoso , Artralgia/etiologia , Efeitos Psicossociais da Doença , Fadiga/etiologia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Mialgia/etiologia , Países Baixos , Doença de Raynaud/etiologia , Esclerodermia Difusa/complicações , Esclerodermia Limitada/complicações , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Índice de Gravidade de Doença , Espanha , Inquéritos e Questionários , Suíça , Reino Unido
14.
Clin Exp Rheumatol ; 32(6 Suppl 86): S-109-14, 2014 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25372796

RESUMO

OBJECTIVES: We sought to examine the relationship between measures of ILD severity and PH in patients with SSc. METHODS: We identified 55 subjects from 12 PHAROS sites with RHC-proven PH and HRCT evidence of ILD. Subjects with PH due to left heart disease were excluded. Baseline HRCT scans were scored by a standardised system that graded severity of ILD. Summary statistics were generated for baseline characteristics. Spearman correlation and linear regression were used to examine relationships between ILD and PH severity variables. RESULTS: The majority of subjects were white women; nearly half had limited cutaneous SSc. Most subjects were New York Heart Association functional class II or III. Pulmonary function testing revealed moderate restriction (mean FVC 64.3 ± 17.2% predicted) with severe reduction in diffusing capacity (mean DLco 34.2 ± 13.3% predicted). RHC demonstrated mild to moderate PH (mean PAP 35 ± 9 mmHg, mean PVR 5.1 ± 3.7 WU). There was no correlation between severity of ILD (by either HRCT or PFT) and cardiac haemodynamic parameters of PH. CONCLUSIONS: No association between severity of ILD and cardiac haemodynamic profiles were identified in this cohort. We believe this underscores the complex nature of PH and ILD in individuals with SSc. We do suspect that some individuals with SSc-ILD will also have concomitant pulmonary vascular disease but simple assessments to grade severity of ILD - by PFT or HRCT estimates of ILD extent - are likely not enough to reliably distinguish between PAH versus PH-ILD. Further research into how to distinguish and manage these subsets is warranted.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pulmão/fisiopatologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Idoso , Teste de Esforço , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Pulmão/diagnóstico por imagem , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar , Esclerodermia Difusa/complicações , Esclerodermia Difusa/diagnóstico por imagem , Esclerodermia Limitada/complicações , Esclerodermia Limitada/diagnóstico por imagem , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Capacidade Vital
15.
Clin Exp Rheumatol ; 32(6 Suppl 86): S-68-74, 2014 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25152080

RESUMO

OBJECTIVES: To analyse the correlation between the number of joint-contractures and other major clinical findings in a follow-up study of 131 patients with systemic sclerosis (SSc). METHODS: The range of motion of joints (ROM), HAQ-DI, and the major clinical characteristics were assessed. RESULTS: A high frequency of contractures (ROM<75% of the normal) were present at baseline in small joints of the hand (82%), wrists (75%), and shoulders (50%). ROM of the dominant side hand was significantly more decreased compared to the non-dominant side. The number of the upper extremity contractures correlated positively with ESR (p<0.01), CRP (p<0.01), HAQ-DI (p<0.01), and negatively with forced vital capacity (FVC) (p<0.05). The number of contractures was not significantly different in cases with early (≤ 4 years) and late disease duration in both the limited and diffuse subgroups. During the three-year follow-up period, an increase in the number of joint contractures (ROM<75%) was associated with an increase of ESR, modified Rodnan's skin score, and the European Scleroderma Study Group Activity Index by multiple linear regression analysis. Univariate analysis over a six-year period demonstrated poor outcome in patients with more than ten contractures, or more than four contractures of unilateral hand-joints. CONCLUSIONS: Contractures predominantly develop during the early years following disease onset in both SSc subgroups. Inflammation and skin-involvement are significant contributing factors for the development of contractures. The dominant hand may be more pronouncedly impaired compared to the non-dominant side. A high number of joint-contractures might be an unfavourable prognostic factor in SSc.


Assuntos
Contratura/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Adulto , Idoso , Articulação do Tornozelo/fisiopatologia , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Estudos de Coortes , Contratura/etiologia , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Articulação da Mão/fisiopatologia , Contratura de Quadril/etiologia , Contratura de Quadril/fisiopatologia , Humanos , Articulação do Joelho/fisiopatologia , Modelos Lineares , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Esclerodermia Difusa/complicações , Esclerodermia Difusa/metabolismo , Esclerodermia Limitada/complicações , Esclerodermia Limitada/metabolismo , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/fisiopatologia , Articulação do Ombro/fisiopatologia , Capacidade Vital
16.
Clin Exp Rheumatol ; 32(6 Suppl 86): S-15-20, 2014 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24850211

RESUMO

OBJECTIVES: In systemic sclerosis (SSc), the frequent involvement of hand and face leads to their disability. We aimed to assess influence of hand and face disability on global disability and Health related Quality of life (HRQoL). METHODS: 119 SSc patients were assessed for global disability by HAQ, HRQoL, by SF36; hand disability by HAMIS, CHFDS, fist closure and hand opening measures; face disability by MHISS and mouth opening measure. RESULTS: Diffuse SSc (dSSc) patients present higher HAQ, lower Summary Physical Index (SPI) of SF36, major hand disability at hand (higher HAMIS, CHFDS, fist closure, lower hand opening) and face (lower mouth opening, higher MHISS) than lSSc patients (p<0.05). SPI of SF36 is negatively correlated with MHISS, CHFDS, HAMIS and positively correlated to mouth and hand opening (p<0.05). Summary Mental Index (SMI) of SF36 is negatively correlated with MHISS (p<0.05). HAQ is negatively correlated with mouth opening and positively correlated to MHISS, HAMIS, CHFDS (p<0.05). By hierarchical multiple linear regression, SPI of SF36 is significantly associated with total MHISS (B=-0.34; t=-3.78; p<0.001) and CHFDS (B=-0.27; t=-3.01; p=0.003), together, explaining 22% of SPI variance. SMI of SF36 is significantly associated only with MHISS total score (B=-0.22; t=-2.41; p=0.017), explaining 4% of its variance. HAQ is significantly associated with CHFDS score (B=0.61; t=7.90; p<0.001), explaining 36% of HAQ variance. CONCLUSIONS: dSSc patients present higher global and local disability, and lower HRQoL in SPI than lSSc patients. Local disabilities, assessed by CHDFS and MHISS, are independently related to global disability and HRQoL.


Assuntos
Dermatoses Faciais/fisiopatologia , Dermatoses da Mão/fisiopatologia , Qualidade de Vida , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Atividades Cotidianas , Idoso , Pessoas com Deficiência , Dermatoses Faciais/psicologia , Feminino , Dermatoses da Mão/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerodermia Difusa/psicologia , Esclerodermia Limitada/psicologia , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/psicologia , Inquéritos e Questionários
17.
Clin Exp Rheumatol ; 32(6 Suppl 86): S-33-40, 2014 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24776173

RESUMO

OBJECTIVES: To compare a cohort of patients with systemic sclerosis sine scleroderma (ssSSc) vs. patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: Forty-five patients with ssSSc and 186 patients with lcSSc were investigated. Demographic, clinical and immunologic features and survival were compared. RESULTS: There were no significant differences between ssSSc and lcSSc in gender, age at onset and interval between onset and diagnosis. ssSSc patients fulfilled the ACR criteria for SSc less than lcSSc patients (13%/77%, p<0.0001). There were no significant differences in articular involvement, myopathy, tendon friction rubs and gastrointestinal, pulmonary, cardiac and renal involvements. There was a trend to higher prevalence of pulmonary arterial hypertension (PAH) in ssSSc patients (29%/19%) but not reach significant difference. The prevalence of antinuclear and anticentromere antibodies and slow capilaroscopic pattern was similar. Sicca syndrome (13%/30%; p=0.024), digital ulcers (16%/50%; p<0.0001), calcinosis (11%/26%; p=0.047) and acroosteolysis (0% /10%; p=0.028) were more frequently in lcSSc. Survival at 5, 10, and 15 yr was not different in ssSSc and lcSSc patients (100%/98%, 100%/98%, and 92%/89%, respectively). CONCLUSIONS: ssSSc and lcSSc patients share demographic, clinical and immunologic features. Survival is also similar in both groups. Differences are mainly due to peripheral vascular manifestations. However, despite great similarities, we believe that ssSSc patients should be considered as a different subset in order to avoid misdiagnosis. ssSSc patients should be truly differentiated from early SSc using sensitive and specific studies looking for any asymptomatic organ involvement.


Assuntos
Calcinose/etiologia , Dermatoses da Mão/etiologia , Hipertensão Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Síndrome de Sjogren/etiologia , Úlcera Cutânea/etiologia , Acro-Osteólise/etiologia , Adulto , Idoso , Transtornos da Motilidade Esofágica/etiologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Esclerodermia Difusa/classificação , Esclerodermia Difusa/complicações , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/classificação , Esclerodermia Limitada/complicações , Esclerodermia Limitada/fisiopatologia , Escleroderma Sistêmico/classificação , Escleroderma Sistêmico/fisiopatologia
18.
G Ital Cardiol (Rome) ; 15(1): 44-50, 2014 Jan.
Artigo em Italiano | MEDLINE | ID: mdl-24503734

RESUMO

BACKGROUND: Heart involvement confers a poor prognosis in patients affected by systemic sclerosis (SSc). Nevertheless, the prevalence of heart involvement in these patients is not fully known. In this study we analyzed the most frequent manifestations of heart involvement at rest in a cohort of patients with SSc, comparing their prevalence in patients with the limited form (lcSSc) and in patients with the diffuse form (dcSSc) of the disease, taking also into account the duration of the disease. METHODS: We thoroughly evaluated with electrocardiographic and echocardiographic examinations 174 patients affected by SSc who were followed at our hospital between 2001 and 2011. They were divided according to the disease subtype (dcSSc vs lcSSc) and information about the disease duration was available for 121 of them (calculated from the onset of the Raynaud's phenomenon). RESULTS: Patients with dcSSc had a greater prevalence of heart involvement at rest when evaluated within 5 and 10 years after the onset of the Raynaud's phenomenon (p=0.0051 within 5 years and p=0.035 within 10 years). Indeed, patients with dcSSc had a greater prevalence of atrioventricular conduction abnormalities within 20 years after the onset of the Raynaud's phenomenon (p=0.03 within 10 years and p=0.04 within 20 years) and a greater prevalence of valvular abnormalities within 5 years (p=0.04). In dcSSc there was a greater prevalence of rhythm disturbances in patients with a disease duration ≤20 or >20 years (p=0.04 within 20 years and p=0.04 after 20 years), but not in those with a disease duration ≤5 and ≤10 years. Left ventricular hypertrophy had a greater prevalence in dcSSc after 20 years of disease duration (p=0.02). CONCLUSIONS: Cardiac manifestation occurs earlier and more frequently in patients affected by dcSSc than in patients with lcSSc.


Assuntos
Cardiopatias/etiologia , Esclerodermia Difusa/complicações , Esclerodermia Limitada/complicações , Adulto , Idoso , Eletrocardiografia , Feminino , Cardiopatias/epidemiologia , Cardiopatias/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Fatores de Tempo
19.
Lancet ; 381(9872): 1116-24, 2013 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-23363664

RESUMO

BACKGROUND: Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. METHODS: We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m(2)) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5-6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. FINDINGS: Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). INTERPRETATION: Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. FUNDING: None.


Assuntos
Causas de Morte , Insuficiência Cardíaca/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Pericardite Constritiva/mortalidade , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Transplante de Células-Tronco de Sangue Periférico/métodos , Esclerodermia Difusa/mortalidade , Esclerodermia Difusa/terapia , Esclerodermia Limitada/mortalidade , Esclerodermia Limitada/terapia , Sepse/mortalidade , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Ensaios de Uso Compassivo , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar/fisiologia , Estudos Retrospectivos , Esclerodermia Difusa/fisiopatologia , Esclerodermia Limitada/fisiopatologia , Capacidade Pulmonar Total , Transplante Autólogo , Capacidade Vital/fisiologia , Adulto Jovem
20.
Arthritis Rheum ; 65(5): 1357-66, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23400395

RESUMO

OBJECTIVE: Pulmonary arterial hypertension (PAH), a common complication of limited cutaneous systemic sclerosis (lcSSc), is associated with alterations of markers of inflammation and vascular damage in peripheral blood mononuclear cells (PBMCs). Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been implicated in autoimmune and inflammatory diseases. The goal of this study was to assess whether markers of ER stress and the UPR are present in PBMCs from lcSSc patients with PAH. METHODS: PBMCs were purified from 36 healthy controls, 32 lcSSc patients with PAH, and 34 lcSSc patients without PAH. Gene expression in healthy control PBMCs stimulated with thapsigargin was analyzed by DNA microarray. Genes were validated by quantitative real-time reverse transcription-polymerase chain reaction in PBMCs from healthy controls and lcSSc patients. RESULTS: Several ER stress/UPR genes, including BiP, activating transcription factor 4 (ATF-4), ATF-6, and a spliced form of X-box binding protein 1, were up-regulated in PBMCs from lcSSc patients, with the highest levels in patients with PAH. Thapsigargin up-regulated heat-shock proteins (HSPs) and interferon (IFN)-regulated genes in PBMCs from healthy controls. Selected HSP genes (particularly DnaJB1) and IFN-related genes were also found at significantly elevated levels in PBMCs from lcSSc patients, while IFN regulatory factor 4 expression was significantly decreased. There was a positive correlation between DnaJB1 and severity of PAH (measured by pulmonary artery pressure) (r = 0.56, P < 0.05) and between ER stress markers and interleukin-6 levels (r = 0.53, P < 0.0001) in PBMCs from lcSSc patients. CONCLUSION: This study demonstrates an association between select ER stress/UPR markers and lcSSc with PAH, suggesting that ER stress and the UPR may contribute to the altered function of circulating immune cells in lcSSc.


Assuntos
Estresse do Retículo Endoplasmático/genética , Hipertensão Pulmonar/genética , Leucócitos Mononucleares/metabolismo , Esclerodermia Limitada/genética , Resposta a Proteínas não Dobradas/genética , Hipertensão Pulmonar Primária Familiar , Regulação da Expressão Gênica , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Leucócitos Mononucleares/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Esclerodermia Limitada/sangue , Esclerodermia Limitada/complicações , Esclerodermia Limitada/fisiopatologia , Índice de Gravidade de Doença , Tapsigargina/farmacologia , Regulação para Cima
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