Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement
Tóm tắt
We investigated early systemic sclerosis (SSc) (that is, Raynaud's phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution. Thirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers. At baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X
2
= 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04). Most early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc.
Tài liệu tham khảo
Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, Kowal-Bielecka O, Müller-Ladner U, Bocelli-Tyndall C, Matucci-Cerinic M: Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis. 2007, 66: 754-763. 10.1136/ard.2006.062901.
Spencer-Green G: Outcomes in primary Raynaud phenomenon: a metaanalysis of the frequency, rates, and predictors of transition to secondary diseases. Arch Intern Med. 1998, 158: 595-600. 10.1001/archinte.158.6.595.
Fine LG, Denton CP, Black CM, Korn JH, de Cambrugge B: Systemic sclerosis: current pathogenetic concepts and future prospects for targeted therapy (Report of a Meeting of Physicians and Scientists, Royal Free Hospital, School of Medicine, London). Lancet. 1996, 347: 1453-1458. 10.1016/S0140-6736(96)91687-6.
LeRoy EC, Medsger TA: Criteria for the classification of early Systemic Sclerosis. J Rheumatol. 2001, 28: 1573-1576.
Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee: Preliminary criteria for classification of systemic sclerosis (scleroderma). Arthritis Rheum. 1980, 23: 581-590. 10.1002/art.1780230510.
Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, Goulet JR, Rich E, Grodzicky T, Raymond Y, Senécal JL: Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis. A twenty-year prospective study of 586 patients with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum. 2008, 58: 3902-3912. 10.1002/art.24038.
LeRoy EC, Medsger TA: Raynaud's phenomenon: a proposal for classification. Clin Exp Rheumatol. 1992, 10: 485-489.
Sebastiani M, Manfredi A, Vukatana G, Moscatelli S, Riato L, Bocci M, Iudici M, Principato A, Mazzuca S, Del Medico P, De Angelis R, D'Amico R, Vicini R, Colaci M, Ferri C: Predictive role of capillaroscopic skin ulcer risk index in systemic sclerosis: a multicentre validation study. Ann Rheum Dis. 2012, 71: 67-70. 10.1136/annrheumdis-2011-200022.
Maricq HR: Widefield capillary microscopy: technique and rating scale for abnormalities seen in scleroderma and related disorders. Arthritis Rheum. 1981, 24: 1159-1165. 10.1002/art.1780240907.
Scussel-Lonzetti L, Joyal F, Raynauld JP, Roussin A, Rich E, Goulet JR, Raymond Y, Senécal JL: Predicting mortality in systemic sclerosis. Analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore). 2002, 81: 154-167. 10.1097/00005792-200203000-00005.
Valentini G, Cuomo G, Abignano G, Petrillo A, Vettori S, Capasso A, Cozzolino D, Del Genio G, Santoriello C: Early systemic sclerosis: assessment of clinical and pre-clinical organ involvement in patients with different disease features. Rheumatology (Oxford). 2011, 50: 317-323. 10.1093/rheumatology/keq176.
Mosca M, Neri R, Bombardieri S: Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria. Clin Exp Rheumatol. 1999, 17: 615-620.
Doria A, Mosca M, Gambari PF, Bombardieri S: Defining unclassifiable connective tissue diseases: incomplete, undifferentiated or both?. J Rheumatol. 2005, 32: 3-5.
Maione S, Cuomo G, Giunta A, Tanturri de Horatio L, La Montagna G, Manguso F, Alagia I, Valentini G: Echocardiographic alterations in systemic sclerosis. A longitudinal study. Semin Arthritis Rheum. 2005, 34: 721-727. 10.1016/j.semarthrit.2004.11.001.
Paone C, Chiarolanza I, Cuomo G, Ruocco L, Vettori S, Menegozzo M, La Montagna G, Valentini G: Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy. Clin Exp Rheumatol. 2007, 25: 613-616.
Steen VD, Owens GR, Fino GJ, Rodnan GP, Medsger TA: Pulmonary involvement in systemic sclerosis (scleroderma). Arthritis Rheum. 1985, 28: 759-767. 10.1002/art.1780280706.
Nakajma K, Taki J, Kawano M, Higuchi T, Sato S, Nishijima C, Takehara K, Tonami N: Diastolic dysfunction in patients with systemic sclerosis detected by gated myocardial perfusion SPECT: an early sign of cardiac involvement. J Nucl Med. 2001, 42: 183-188.
Sjogren RW: Gastrointestinal motility disorders in scleroderma. Arthritis Rheum. 1994, 37: 1265-1282. 10.1002/art.1780370902.
Harper FE, Maricq HR, Turner RE, Lidman RW, LeRoy EC: A prospective study of Raynaud phenomenon and early connective tissue disease. A five-year report. Am J Med. 1982, 72: 883-888. 10.1016/0002-9343(82)90846-4.
Kallenberg CGM, Pastoor GW, Wouda AA, The TH: Antinuclear antibodies in patients with Raynaud's phenomenon: clinical significance of anticentromere antibodies. Ann Rheum Dis. 1982, 41: 382-387. 10.1136/ard.41.4.382.
Gerbracht DD, Steen VD, Ziegler GL, Medsger TA, Rodnan GP: Evolution of primary Raynaud's phenomenon (Raynaud's disease) to connective tissue disease. Arthritis Rheum. 1985, 28: 87-92. 10.1002/art.1780280114.
Fitzgerald O, Hess EV, O'Connor GT, Spencer-Green G: Prospective study of the evolution of Raynaud's phenomenon. Am J Med. 1988, 84: 718-726. 10.1016/0002-9343(88)90109-X.
Kallenberg CG, Wouda AA, Hoet MH, Van Venrooij WJ: Development of connective tissue disease in patients presenting with Raynaud's phenomenon: a six year follow up with emphasis on the predictive value of antinuclear antibodies as detected by immunoblotting. Ann Rheum Dis. 1988, 47: 634-641. 10.1136/ard.47.8.634.
Luggen M, Belhorn L, Evans T, Fitzgerald O, Spencer-Green G: The evolution of Raynaud's phenomenon: a longterm prospective study. J Rheumatol. 1995, 22: 2226-2232.
Hirschl M, Hirschl K, Lenz M, Katzenschlager R, Hutter H-P, Kundi M: Transition from primary Raynaud's phenomenon to secondary Raynaud's phenomenon identified by diagnosis of an associated disease. Results of ten years of prospective surveillance. Arthritis Rheum. 2006, 54: 1974-1981. 10.1002/art.21912.
Ingegnoli F, Boracchi P, Gualtierotti R, Lubatti C, Meani L, Zahalkova L, Zeni S, Fantini F: A prognostic model based on nailfold capillaroscopy for identifying Raynaud's phenomenon patients at high risk for the development of a scleroderma spectrum disorders. Arthritis Rheum. 2008, 58: 2174-2182. 10.1002/art.23555.
Giordano M, Valentini G, Migliaresi S, Picillo U, Vatti M: Different antibody patterns and different prognoses in patients with scleroderma with various extent of skin sclerosis. J Rheumatol. 1986, 13: 911-916.
Avouac J, Fransen J, Walker UA, Riccieri V, Smith V, Muller C, Miniati I, Tarner IH, Randone SB, Cutolo M, Allanore Y, Distler O, Valentini G, Czirjak L, Müller-Ladner U, Furst DE, Tyndall A, Matucci-Cerinic M, EUSTAR Group: Ann Rheum Dis. 2011, 70: 476-481. 10.1136/ard.2010.136929.