Microangiopatia em pacientes com esclerose sistêmica: estudo prospectivo em pacientes com doença precoce e estabelecida

• Autor(a) principal: Camargo, Cintia Zumstein [UNIFESP]
• Data de Publicação: 2018
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6320801; https://repositorio.unifesp.br/handle/11600/52286
• topic: Fenômeno de Raynaud; Capilaroscopia; Laser doppler imaging; Estudo prospectivo; Esclerose sistêmica; Fenômeno de Raynaud; Capilaroscopia; Laser doppler imaging; Estudo prospectivo; Esclerose sistêmica

Introduction: Systemic Sclerosis (SSc) is a chronic autoimmune disease, characterized by microangiopathy and fibrosis of the skin and internal organs, whose diagnosis in early stages remains a challenge. In 2001 LeRoy and Medsger proposed criteria for the classification of early SSc defined by the presence of Raynaud's phenomenon (RP), capillaroscopy abnormalities and specific autoantibodies. Recently, new criteria for the classification of SSc have been proposed by the ACR/EULAR, which include manifestations present in the early and late stages of the disease. Despite the importance of the early diagnosis of SSc, few studies have evaluated the incidence and risk factors associated with the development of definite SSc in patients with early SSc, as well as the risk factors associated with disease progression in patients with definite disease. Widefield nailfold capillaroscopy (NFC) and videocapillaroscopy are methods that evaluate anatomical changes of the microcirculation in patients with RP. Laser Doppler imaging (LDI) is a method of measurement of superficial microvascular blood flow. Objective: Evaluation of clinical and laboratorial risk factors for progression to definite disease in early SSc patients, as well for disease progression in patients with definite disease in a follow up of 3 years. In addition, the longitudinal abnormalities in the microcirculation were evaluated in patients with definite and early SSc. Patients and methods: In this prospective study, patients with definite SSc (n=80) (ACR/EULAR 2013 criteria) and patients with early SSc (n=46) (LeRoy and Medsger 2001 criteria) were evaluated at baseline and after 3 years of follow-up. Clinical data, widefield NFC and videcapillaroscopy (parameters evaluated: number of capillaries / mm, number of enlarged capillaries, giant capillaries, ramified capillaries, microhaemorrhages and avascular score) were collected in all subjects at baseline and at the end of the follow-up. The mean finger blood flow (FBF) measured by LDI (before and after cold stimulus), and serum levels of von Willebrand factor were also evaluated. Worsening of the number of giant capillaries was considered when there was an increase in the mean number of giant capillaries greater or equivalent to 0.1 for early SSc and greater or equivalent to 0.3 for definite SSc. The scleroderma pattern was classified as early, active and late. Results: At the end of 3 years (38.4 ± 4.1 months), 60 patients with definite SSc (mean age 54 ± 14.2 years) and 34 patients with early SSc (mean age 53 ± 12.7 years) were reevaluated. Of the patients with early SSc, 23.5% developed definite SSc. Any worsening in widefield NFC and videocapillaroscopy was observed in 55.9% and 67.6% of the patients with early SSc, respectively. In patients with definite SSc, worsening was observed in 91.7% in widefield NFC and 95% in videocapillaroscopy. An increase in the number of giant capillaries and worsening in the avascular score were more frequent in patients who developed SSc (p=0.02 and p=0.002 in widefield NFC, respectively). By multivariate analysis, an active or late pattern in NFC at baseline (OR = 30.0, p = 0.01), was an independent predictor for the development of definite SSc in patients with early SSc. On the other hand, worsening of the number of giant capillaries in both widefield NFC (OR = 8.69, p = 0.03) and videocapillaroscopy (OR = 6.92, p = 0.05), male sex (OR = 40.55, p = 0.01) and elevated vWF levels (OR = 1.03, p = 0.03) were independent predictors for the development of new digital ulcers in patients with definite SSc. Overall disease progression in patients with definite SSc was associated with diffuse cutaneous form (OR = 3.00; p=0.048), lower fingertip blood flow (OR = 0.99, p=0.03) and worsening of number of capillaries/mm in widefield NFC (OR=3.48, p=0.04). At the end of follow-up, there was a significant increase in the number of enlarged capillaries in patients with early SSc and definite SSc, while an increase in the avascular score was observed only in patients with definite SSc. Conclusions: In this prospective study in which both patients with early SSc and patients with defined SSc were evaluated, active or late pattern in capillaroscopy was an independent risk factor for the development of definite SSc in patients with early SSc. Worsening of capillaroscopy parameters influenced the development of new digital ulcers and overall disease progression in patients with definite SSc.