Información del artículo
Resumen
La esclerosis sistémica es una enfermedad autoinmune del tejido conectivo, que se caracteriza por un depósito excesivo de tejido colágeno y otros componentes de la matriz extracelular en la piel así como en otros órganos internos, principalmente en el pulmón, el riñón y el tracto gastrointestinal. Las úlceras digitales se consideran por su morbilidad como una complicación frecuente y grave de la esclerosis sistémica, y se estima que afectan a la mitad de los pacientes en algún momento evolutivo de su enfermedad, tanto en la forma difusa como en la limitada, y representan la expresión extrema de la isquemia en partes acras. El mecanismo patogénico implicado varía en función de la localización de la lesión. Estudios recientes han demostrado la correlación que hay entre el patrón de capilaroscopia del lecho periungueal y la afectación vascular periférica como las úlceras digitales. El tratamiento incluye medidas farmacológicas y no farmacológicas, basándose principalmente en el control de cada uno de los mecanismos implicados en su genesis y prestando especial atención al control y óptimo tratamiento del fenómeno de Raynaud.
Palabras clave:
Esclerosis sistémica
Úlceras digitales
Tratamiento
Abstract
Systemic sclerosis is an autoimmune disease of the connective tissue characterized by an excessive deposit of collagen and other components of the extracellular matrix in the skin as well as in other internal organs, mainly in lung, gastrointestinal tract and kidney. Digital ulcers are considered by their morbidity as severe and frequent complication in systemic sclerosis. These lesions are extremely painful, heal slowly and lead to substantial functional disability. The pathogenesis of digital ulcers differs depending on their location and occurs in up to half of all patients with limited or diffuse systemic sclerosis at some point during their disease. Recent studies have demonstrated a correlation between the nailfold capillaroscopic pattern and the peripheral vascular involvement as well as with digital ulcers. Treatment includes pharmalogical and non-pharmacological measures, mainly based on controlling each of the mechanisms involved in their genesis and optimal treatment of the Raynaud phenomenon.
Key words:
Systemic sclerosis
Digital ulcers
Treatment
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Bibliografía
[1.]
C.P. Denton, C.M. Black, D.J. Abraham.
Mechanisms and consequences of fibrosis in systemic sclerosis [review].
Nat Clin Pract Rheumatol, 2 (2006), pp. 134-144
[2.]
C. Charles, P. Clemens, D.E. Furst.
Systemic sclerosis hypothesis-driven treatment strategies [review].
Lancet, 367 (2006), pp. 1683-1691
[3.]
C.P. Denton, J.H. Korn.
Digital ulceration and critical digital ischemia in scleroderma.
Scleroderma Care and Research, 1 (2003), pp. 12-16
[4.]
S. Sato, M. Fujimoto, M. Hasegawa, et al.
Altered B lymphocyte function induces systemic autoimmunity in systemic sclerosis.
Mol Immunol, 42 (2005), pp. 821-831
[5.]
S. Sato, M. Fujimoto, M. Hasegawa.
Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells.
Arthritis Rheum, 50 (2004), pp. 1918-1927
[6.]
M. Hasegawa, M. Fujimoto, K. Takehara, S. Sato.
Pathogenesis of systemic sclerosis: altered B cell function is the key linking systemic autoimmunity and tissue fibrosis [review].
J Dermatol Sci, 39 (2005), pp. 1-7
[7.]
H. Ihn.
Scleroderma, fibroblasts, signaling, and excessive extracellular matrix.
Curr Rheumatol Rep, 7 (2005), pp. 156-162
[8.]
E.C. LeRoy.
Increased collagen synthesis by scleroderma fibroblasts in vitro A possible defect in the regulation or activation of the scleroderma fibroblast.
J Clin Invest, 54 (1974), pp. 880-889
[9.]
C. Ferri, G. Valentini, F. Cozzi, M. Sebastiani, C. Michelassi, G. La Montagna, Systemic Sclerosis Study group of the Italian Society of Rheumatology, et al.
Systemic sclerosis: demographic, clinical and serologic features and survival in 1012 Italian patients.
Medicine (Baltimore), 81 (2002), pp. 139-153
[10.]
A.H. Mawdsley.
Patient perception of UK scleroderma services Results of an anonymous questionnaire.
Rheumatology, 45 (2006), pp. 1573
[11.]
A.C. Gelber, F.M. Wigley, R.Y. Stallings.
Symptoms of Raynaud phenomenon in an inner-city African-American community.
J Clin Epidemiol, 52 (1999), pp. 441
[12.]
J.A. Block, W. Sequeira.
Raynaud's phenomenon.
Lancet, 375 (2001), pp. 2042
[13.]
H.R. Maricq, P.H. Carpentier, M.C. Weinrich, et al.
Geographic variation in the prevalence of Raynaud phenomenon.
J Reumatol, 20 (1993), pp. 70
[14.]
J.A. Román Ivorra, J.L. Gonzálvez, C. Fernández, et al.
Prevalence of Raynaud phenomenon in general practice in the east of Spain.
Clin Rheumatol, 20 (2001), pp. 88
[15.]
G. Riera, M. Vilardell, J. Vaqué, V. Fonollosa, B. Bermejo.
Prevalence of Raynaud's phenomenon in a healthy Spanish population.
J Rheumatol, 20 (1993), pp. 66-69
[16.]
D. Estes, C.L. Christian.
The natural history of systemic lupus erythematosus by prospective analysis.
Medicine (Baltimore), 50 (1971), pp. 85-95
[17.]
M.C. Hochberg, R.E. Boyd, J.M. Ahearn, F.C. Arnett, W.B. Bias, T.T. Provost, et al.
Systemic lupus erythematosus: a review of clinico-laboratory features and immunogenetic markers in 150 patients.
Medicine (Baltimore), 64 (1985), pp. 285-295
[18.]
M. García-Carrasco, A. Sisó, M. Ramos-Casalas, J. Rosas, G. De la Red, V. Gil.
Raynaud's phenomenon in primary Sjögres syndrome. Prevalence and clinical characteristics in a series of 320 patients.
J Rheumatol, 29 (2002), pp. 726-730
[19.]
A. Saraux, J. Allain, C. Guedes, D. Baron, P. Youinou, P. Le Goff.
Raynaud's phenomenon in rheumatoid arthritis.
Br J Rheumatol, 35 (1996), pp. 752-754
[20.]
R.W. Hoffman, E.L. Greidinger.
Mixed connective tissue disease.
Curr Opin Rheumatol, 12 (2000), pp. 386-390
[21.]
R.M. Silver, H.R. Maricq.
Childhood dermatomyositis: serial microvascular studies.
Pediatrics, 83 (1989), pp. 278-283
[22.]
F.M. Wigley.
Clinical practice. Raynaud's Phenomenon.
N Engl J Med, 347 (2002), pp. 1001
[23.]
M.A. Burdt, R.W. Hoffman, S.L. Deutscher, et al.
Long-term outcome in mixed connective tissue disease: longitudinal, clinical and serologic findings.
Arthritis Rheum, 42 (1999), pp. 899-909
[24.]
F.M. Wigley, N.A. Flavahan.
Raynaud's phenomenon.
Rheum Dis Clin North Am, 22 (1996), pp. 765
[25.]
S.I. Nihtyanova, C.M. Black, C.P. Denton.
Clinical burden of digital vasculopathy in limited and diffuse cutaneous systemic sclerosis.
Ann Rheum Dis, 67 (2008), pp. 120-123
[26.]
S. Guiducci, R. Giacomelli, M.C. Matucci.
Vascular complications of scleroderma.
Autoimmunity Reviews, 6 (2007), pp. 20
[27.]
W. Grassi, P.D. Medico, F. Izzo, C. Cervini.
Microvascular involvement in Systemic Sclerosis: capillaroscopic findings.
Semin Arthritis Rheum, 30 (2001), pp. 397-402
[28.]
H.R. Maricq, F.E. Harper, M.M. Khan, E.M. Tan, E.C. LeRoy.
Microvascular abnormalities as possible predictors of disease subset in Raynaud's phenomenon and early connective tissue disease.
Clin Exp Rheumatol, 1 (1983), pp. 195-205
[29.]
D.D. Gerbracht, V.D. Steen, G.L. Ziegler, T.A. Medsger, G.P. Rodnan.
Evolution of primary Raynaud's phenomenon to connective tissue disease.
Arthritis Rheum, 28 (1985), pp. 87-92
[30.]
H.J. Anders, T. Sigl, M. Schattenkirchner.
Differentiation between primary and secondary Raynaud phenomenon.
Ann Rheum Dis, 60 (2001), pp. 407-409
[31.]
H.R. Maricq, E.C. LeRoy, W.A. D’Angelo, et al.
Diagnostic potential of in vivo capillary microscopy in scleroderma and related disorders.
Arthritis Rheum, 23 (1980), pp. 183-189
[32.]
P.M. Houtman, C.G.M. Callemberg, V. Fidler, A.A. Wouda.
Diagnostic significance of nailfold capillary patterns in patients with Raynaud's phenomenon.
J Rheumatol, 13 (1986), pp. 556-563
[33.]
E. Mannatimo, L. Pacualini, F. Fedeli, V. Scricciolo, S. Inocente.
Nailfold capillaroscopy in the screening and diagnosis of Raynaud's phenomenon.
Angiology, 45 (1994), pp. 37-42
[34.]
P. Lee, J. Sarkocy, A.A. Bookman, F. Keystone, S.K. Armstrong.
Digital blood flow and nailfold capillary microscopy in Raynaud's phenomenon.
J Rheumatol, 13 (1986), pp. 564-569
[35.]
H. Maricq, E.C. LeRoy.
Patterns of finger capillary abnormalities in connective tissue disese by “Wide-field” microscopy.
Arthritis Rheum, 16 (1973), pp. 619-628
[36.]
H. Knobel, M. Vilardell, R. Marquet, J. Ordi.
La capilaroscopia del lecho periungueal en el fenómeno de Raynaud y la esclerodermia.
Med Clin (Barc), 89 (1987), pp. 533
[37.]
M. Cutolo, A. Sulli, C. Pizzorni, S. Accardo.
Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis.
J Rheumatol, 27 (2000), pp. 155-160
[38.]
F. Martino, D. Agolini, E. Tsalikova, et al.
Nailfold capillaroscopy in Henoch-Schonlein purpura: a follow-up study of 31 cases.
J Pediatr, (2002), pp. 141-145
[39.]
W. Grassi, P.D. Medico, F. Izzo, C. Cervini.
Microvascular involvement in Systemic Sclerosis: capillaroscopic findings.
Semin Arthritis Rheum, 30 (2001), pp. 397-402
[40.]
A. Sulli, A. Burroni, M. Tuccio, C. Pizzorni, C. Craviotto, M. Ghio, et al.
La videocapillaroscopia periungueale nella sclerosis sistemica: parametri diagnostici e di follow-up della malalttia e correlazione con il tipo di impegno cutáneo e con gli autoanticorpi specifici.
Reumatismo, 56 (2004), pp. 34-45
[41.]
M. Cutolo, C. Pizzorni, M. Tuccio, A. Burroni, C. Craviotto, M. Basso, et al.
Nailfold videocapillaroscopic patterns and serum autoantibodies in systemic sclerosis.
Rheumatology, 43 (2004), pp. 719-726
[42.]
M. Cutolo, C. Pizzorni, A. Sulli.
Nailfold video-capillaroscopy in systemic-sclerosis.
Z Rheumatol, 63 (2004), pp. 457-462
[43.]
E. Beltrán-Catalán, A. Toll, A. Pros, J. Carbonell, R.M. Pujol.
Assessment of nailfold capillaroscopy by x30 digital epiluminiscence (dermoscopy) in patients with Raynaud phenomenon.
Br J Dermatol, 156 (2007), pp. 892
[44.]
Z. Nagy, L. Czirjak.
Nailfold digital capillaroscopy in 447 patients with connective tissue disease and Raynaud's disease.
J Eur Acat Dermatol Venerol, 18 (2004), pp. 62-68
[45.]
T. Grader-Beck, F.M. Wigley.
Raynaud's phenomenon in mixed connective tissue disease.
Rheum Dis Clin N Am, 31 (2005), pp. 465-481
[46.]
M. Keberle, H.P. Tony, R. Jahns, M. Hau, R. Haerten, M. Jenett.
Assessment of microvascular changes in Raynaud's phenomenon and connective tissue disease using colour Doppler ultrasound.
Rheumatology, 39 (2000), pp. 1206-1213
[47.]
S. Caramaschi, N. Canestrini, A. Martinelli, et al.
Scleroderma patients nailfold videocapillarooscopic patterns associated with disease subset and disease severity.
Rheumatology, 10 (2007), pp. 1093
[48.]
M. Cutolo, W. Grassi, M.M. Cerinic.
Raynaud's Phenomenon and the role of capillaroscopy.
Arthritis Rheum, 48 (2003), pp. 3023-3030
[49.]
L. Chung.
Therapeutic options for digital ulcers in patients with systemic sclerosis [review].
JDDG, 5 (2007), pp. 460
[50.]
P. Ostjic, N. Damjanov.
Different clinical features in patients with limited and diffuse cutaneous systemic sclerosis.
Clin Rheumatol, 25 (2006), pp. 453-457
[51.]
F. Tiso, L. Favaro, S. Ciprian, et al.
Ulcere digitali in una coorte di 333 pazienti sclerodermici.
Reumatismo, 59 (2007), pp. 215
[52.]
C. Ferri, G. Valentini, F. Cozzi, et al.
Systemic sclerosis: demographic, clinical and serologic features and survival in 1012 italian patients.
Medicine, 81 (2002), pp. 139-153
[53.]
U.A. Walker, A. Tyndall, L. Czirjak, et al.
Clinical risk assessment of organ manifestations in systemic sclerosis. A report from the EULAR Scleroderma Trials And Research (EUSTAR) data group.
Ann Rheum Dis, 66 (2007), pp. 754
[54.]
P. Ostjic, N. Damjanov, S. Pavlov.
Peripheral vasculopathy in patients with systemic sclerosis: difference in limited and diffuse subset of disease.
Clin Hemorheol Microcirc, 31 (2004), pp. 281
[55.]
V.D. Steen.
Autoantibodies in systemic sclerosis.
Semin Arthritis Rheum, 35 (2005), pp. 35-42
[56.]
M. Wigley, R.A. Wise, R. Miller, et al.
Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis.
Arthritis Rheum, 35 (1992), pp. 688
[57.]
T.A. Medsger Jr.
Systemic sclerosis (scleroderma): Clinical aspects.
Arthritis and allied conditions, pp. 1433-1464
[58.]
E.C. LeRoy.
Pathogenesis of systemic sclerosis (scleroderma).
Arthritis and allied conditions, pp. 1481-1490
[59.]
L.K. Hummers, F.M. Wigley.
Management of Raynaud's phenomenon and digital ischemic lesions in scleroderma.
Rheum Dis Clin North Am, 29 (2003), pp. 293-313
[60.]
P. Merkel, K. Herlyn, R. Martin, et al.
Measuring disease activity and functional status in patients with scleroderms and Raynaud's phenomenon.
Arthritis Rheum, 46 (2002), pp. 2410-2420
[61.]
G. Rodnan, R. Myerowitz, G. Justh.
Morphologic changes in the digital arteries of patients with progressive systemic sclerosis and Raynaud phenomenon.
Medicine, 59 (1980), pp. 393-408
[62.]
C. Lau, M. McLaren, A. Sanibadi, et al.
Increased whole blood platelet aggregation in patients with Raynaud's phenomenon with or without systemic sclerosis.
Scand J Rheumatol, 22 (1993), pp. 97
[63.]
M. Worda, R. Sgonc, H. Dietrich, et al.
In vivo analysis of the apoptosis-inducing effect of anti-endothelial cell antibodies in systemic sclerosis by the chorionallantonic membrane assay.
Arthritis Rheum, 48 (2003), pp. 2605-2614
[64.]
G.N. Anderson, L. Mincheva-Nilsson, E. Kazzam, et al.
Assessment of vascular function in systemic sclerosis: indications of the development of nitrate tolerance as a result on enhanced endothelial nitric oxide production.
Arthritis Rheum, 46 (2002), pp. 1324
[65.]
E.C. LeRoy.
Systemic sclerosis: a vascular perspective [review].
Rheum Dis Clin North Am, 22 (1996), pp. 675-694
[66.]
M.B. Kahaleh.
Vascular involvement in systemic sclerosis [review].
Clin Exp Rheumatol, 22 (2004), pp. S19-S33
[67.]
R. Sgonc, M.S. Gruschwitz, H. Dietrich, et al.
Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma.
J Clin Invest, 98 (1996), pp. 785-792
[68.]
R. Sgonc, M.S. Gruschwitz, G. Boeck, et al.
Endothelial cell apoptosis in systemic sclerosis is induced by antibody-dependent cell-mediated cytotoxicity via CD95.
Arthritis Rheum, 43 (2000), pp. 2550-2562
[69.]
M.D. Mayes.
Endothelin and endothelin receptor antagonists in systemic rheumatic diseases [review].
Arthritis Rheum, 48 (2003), pp. 1190-1199
[70.]
E.R. Levin.
Endothelins.
N Engl J Med, 333 (1995), pp. 356-363
[71.]
M.B. Kahaleh.
Endothelin: an endothelial-dependent vasoconstrictor in scleroderma.
Arthritis Rheum, 34 (1991), pp. 978
[72.]
N.A. Flavahan, S. Flavahan, Q. Liu, et al.
Increased alfa-2 adrenergic constriction of isolated arterioles in diffuse scleroderma.
Arthritis Rheum, 43 (2000), pp. 1886-1890
[73.]
J.D. Coffman, R.A. Cohen.
Role of alfa-adrenoreceptor subtypes mediating sympathetic vasoconstriction in human digits.
Eur J Clin Invest, 18 (1988), pp. 309
[74.]
R.R. Freedman, R. Girgis, M.D. Mayes.
Endothelial and adrenergic dysfunction in Raynaud's phenomeon and scleroderma.
J Rheumatol, 26 (1999), pp. 2386
[75.]
B. Kahaleh, O. Meyer, R. Scorza.
Assessment of vascular involvement.
Clin Exp Rheumatol, 21 (2003), pp. S9-S14
[76.]
D. Carvalho, C.O. Savage, C.M. Black, J.D. Pearson.
IgG antiendothelial cell autoantibodies from scleroderma patients induce leukocyte adhesion to human vascular endothelial cells in vitro. Induction of adhesion molecule expression and involvement of endothelium-derived cytokines.
J Clin Invest, 97 (1996), pp. 111
[77.]
M. Worda, R. Sgonc, H. Dietrich, et al.
In vivo analysis of the apoptosis-inducing effect of anti-endothelial cell antibodies in systemic sclerosis by the chorionallantoic membrane assay.
Arthritis Rheum, 48 (2003), pp. 2605
[78.]
S.S. Ahmed, F.K. Tan, F.C. Arnett, et al.
Induction of apoptosis and fibrillin 1 expression in human dermal endothelial cells by scleroderma sera containing anti-endothelial cell antibodies.
Arthritis Rheum, 54 (2006), pp. 2250
[79.]
V.S. Negi, N.K. Tripathy, R. Mirsa, et al.
Antiendothelial cell antibodies in scleroderma correlated with severe digital ischemia and pulmonary arterial hypertension.
J Rheumatol, 25 (1998), pp. 462
[80.]
A. Pigione, C. Scaletti, M. Matucci-Cerinic, et al.
Anti-endothelial cell antibodies in systemic sclerosis: significant association with vascular involvement and alveolocapillary impairment.
Clin Exp Rheumatol, 16 (1998), pp. 527
[81.]
L. Chung, D. Fiorentino.
Digital ulcers in patients with systemic sclerosis.
Autoimmunity Reviews, 5 (2006), pp. 125
[82.]
N.S. Sherber, F.M. Wigley, R.K. Scher.
Autoimmune disorders: nail signs and therapeutic approaches.
Dermatologic Therapy, 20 (2007), pp. 17-30
[83.]
P. Rich, R.K. Scher.
An atlas of diseases of the nail.
Parthenon Publishing, (2003),
[84.]
R.K. Scher, C.R. Daniel III.
Nails: Therapy, diagnosis, surgery.
3rd ed., W.B. Saunders Co., (2005),
[85.]
A.J. Marshal, C.J.C. Roberts, D.W. Barritt.
Raynaud's phenomenon as side effect of beta-blockers in hypertension.
Br Med J, 1 (1976), pp. 1498
[86.]
C. Franssen, H. Wollersheim, A. DeHaan, et al.
The influence of different beta-blocking drugs on the peripheral circulation in Raynaud phenomenon and in hypertension.
J Clin Pharmacol, 32 (1992), pp. 652
[87.]
J. Sauza, A. Kraus, R. González-Amaro, et al.
Effect of the calcium channel blocker nifedipine on Raynaud's phenomenon. A controlled double-blind trial.
J Rheumatol, 11 (1984), pp. 362
[88.]
D.C. Smith, R.J.R. McKendry.
Controlled trial of nifedipine in the treatment of Raynaud's phenomenon.
Lancet, 2 (1982), pp. 1299-1301
[89.]
A.E. Thompson, B. Shea, V. Welch, et al.
Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis.
Arthritis Rheum, 44 (2001), pp. 1841
[90.]
A.E. Thompson, J.E. Pope.
Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis.
Rheumatology (Oxford), 44 (2005), pp. 145
[91.]
M. Rademaker, E.D. Cooke, N.E. Almond, et al.
Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.
BMJ, 298 (1989), pp. 561
[92.]
C.J. White, W.A. Phillips, L.A. Abrahams, et al.
Objective benefit of nifedipine in the treatment of Raynaud's phenomenon: Double-blinded controlled study.
Am J Med, 80 (1986), pp. 623
[93.]
L. La Civita, N. Pitaro, M. Rossi, et al.
Amlodipine in the treatment of Raynaud's phenomenon.
Br J Rheumatol, 32 (1993), pp. 524
[94.]
C.G. Kallenberg, A.A. Wonda, L. Meems, H. Wesseling.
Once daily felodipine in patient with primary Raynaud's phenomenon.
Eur J Clin Pharmacol, 40 (1991), pp. 313
[95.]
V.F. Challenor.
Angiotensin converting enzyme inhibitors in Raynaud's phenomenon.
Drugs, 48 (1994), pp. 864
[96.]
H.M. Wood, M.E. Ernst.
Renin-angiotensin system mediators and Raynaud's phenomenon [review].
Ann Pharmacother, 40 (2006), pp. 1998-2002
[97.]
M. Dziadzio, C.P. Denton, R. Smith, et al.
Losartan therapy for Raynaud's phenomenon and scleroderma.
Arthritis Rheum, 42 (1999), pp. 2646
[98.]
S. Tosi, A. Marchesoni, K. Messina, et al.
Treatment of Raynaud's phenomenon with captopril.
Drugs Exp Clin Res, 13 (1987), pp. 37
[99.]
J.B. Warren, K. Rashpal.
Captopril increases skin microvascular blood flow secondary to bradykinin, nitric oxide and prostaglandins.
FASEB J, 9 (1995), pp. 411
[100.]
V.F. Challenor, D.G. Waller, R.A. Hayward, M.J. Griffin, O.S. Roath.
Subjective and objective assessment of enalapril in primary Raynaud's phenomenon.
Br J Clin Pharmacol, 31 (1991), pp. 477-480
[101.]
S.D. Janini, D.G. Scott, J.S. Coppock, P.A. Bacon, M.J. Kendall.
Enalapril in Raynaud's phenomenon.
J Clin Pharm Ther, 13 (1988), pp. 145-150
[102.]
L. Russell, J.A. Lessard.
Prazosin treatment of Raynaud's phenomenon: A double-blind single crossover study.
J Rheumatol, 12 (1985), pp. 94
[103.]
H. Wollersheim, T. Thien, J. Fennis, et al.
Double-blind, placebo controlled study of prazosin in Raynaud's phenomenon.
Clin Pharmacol Ther, 40 (1986), pp. 219
[104.]
R.A. Wise, F.M. Wigley, B. White, et al.
Efficacy and tolerability of a selective alpha(2C)-adrenergic receptor blocker in recovery from cold-induced vasospasm in scleroderma patients: a single-center, double-blind, placebo-controlled, randomized crossover study.
Arthritis Rheum, 50 (2004), pp. 3994
[105.]
P. Langevitz, D. Buskila, P. Lee, et al.
Treatment of refractory ischemic skin ulcers in patients with Raynaud's phenomenon with PGE, infusions.
J Rheumatol, 16 (1989), pp. 1433
[106.]
J.S. Mohrland, J.M. Porter, E.A. Smith, et al.
A multiclinic, placebo-controlled, double-blind study of Prostaglandin Raynaud's syndrome.
Ann Rheum Dis, 44 (1985), pp. 754
[107.]
P.M. Dowd, M.F. Martin, E.D. Cooke, et al.
Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin (PGI2).
Br J Dermatol, 106 (1982), pp. 81
[108.]
M. Gardinali, M.R. Pozzi, M. Bernareggi, N. Montani, E. Allevi, L. Catena, et al.
Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis.
J Rheumatol, 28 (2001), pp. 786-794
[109.]
S. Bartolone, A. Trifiletti, G. De Nuzzo, R. Scamardi, D. Larosa, G. Sottilotta, et al.
Efficacy evaluation of prostaglandin E1 against placebo in patients with progressive systemic sclerosis and significant Raynaud's phenomenon.
Minerva Cardioangiol, 47 (1999), pp. 137-143
[110.]
M.V. Kyle, G. Belcher, B.L. Hazleman.
Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud's phenomenon.
J Rheumatol, 19 (1992), pp. 1403
[111.]
F.M. Wigley, J.R. Seibold, R.A. Wise, et al.
Intravenous iloprost treatment of Raynaud's phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, doubleblind study.
Ann Intern Med, 120 (1994), pp. 199
[112.]
L. Bettoni, A. Geri, P. Airo, et al.
Systemic sclerosis therapy with iloprost: a prospective observational study of 30 patients treated for a median of 3 years.
Clin Rheumatol, 21 (2002), pp. 244
[113.]
F.M. Wigley, J.R. Seibold, R.A. Wise, D.A. McCloskey, W.P. Dole.
Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis.
J Rheumatol, 19 (1992), pp. 1407-1414
[114.]
J. Pope, D. Fenlon, A. Thompson, B. Shea.
Iloprost and cisaprost for Raynaud's phenomenon in progressive systemic sclerosis.
Cochrane Database Syst Rev, 2 (2000),
[115.]
F. Zulian, F. Corona, V. Gerloni, F. Falcini, A. Buoncompagni, M. Scarazatti, et al.
Safety and efficacy of iloprost for the treatment of ischaemic digits in paediatric connective tissue diseases.
Rheumatology (Oxford), 43 (2004), pp. 229-233
[116.]
L. Bettoni, A. Geri, P. Airo, E. Danieli, I. Cavazzana, C. Antonioli, et al.
Systemic sclerosis therapy with iloprost: a prospective observational study of 30 patients treated for a median of 3 years.
Clin Rheumatol, 21 (2002), pp. 244-250
[117.]
F.J. García Hernández, C. Ocana Medina, L. Mateos Romero, J. Molinillo López, A. Arias Zambrano, R. González León, et al.
Iloprost for severe Raynaud's phenomenon and ischemic ulcers related with systemic diseases.
Med Clin (Barc), 122 (2004), pp. 501-504
[118.]
F.M. Wigley, J.H. Korn, M.E. Csuka, T.A. Medsger, N.F. Rothfield, M. Ellman, et al.
Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: a multicenter, placebo-controlled, double-blind study.
Arthritis Rheum, 41 (1998), pp. 670-677
[119.]
P. Lamprecht, A. Schnabel, W.L. Gross.
Efficacy of alprostadil and iloprost in digital necrosis due to secondary Raynaud's phenomenon.
Br J Rheumatol, 37 (1998), pp. 703
[120.]
E. Beltrán-Catalán, A. Pros Simón, C. Pérez García, P. Benito Ruiz.
Treatment of severe Raynaud's phenomenon in collagen diseases with alprostadil IV.
Ann Rheum Dis, 64 (2005), pp. S304
[121.]
B. Marasini, M. Massarotti, B. Bottasso, R. Coppola, N.D. Papa, W. Maglione, et al.
Comparison between iloprost and alprostadil in the treatment of Raynaud's phenomenon.
Scand J Rheumatol, 33 (2004), pp. 253-256
[122.]
J.J.F. Belch, J.K. Drury, H. Capell, et al.
Intermittent epoprostenol (prostacyclin) infusion in patients with Raynaud's syndrome: A double-blind controlled trial.
Lancet, 1 (1983), pp. 313-315
[123.]
D.B. Badesch, V.F. Tapson, M.D. McGoon, et al.
Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.
Ann Intern Med, 132 (2000), pp. 425
[124.]
L. Chung, D. Fiorentino.
A pilot trial of treprostinil for the treatment and prevention of digital ulcers in patients with systemic sclerosis.
J Am Acad of Dermatol, 54 (2006), pp. 880
[125.]
G. Engel, S.G. Rockson.
Treprostinil for the treatment of severe digital necrosis in systemic sclerosis.
Vascular Medicine, 10 (2005), pp. 29-32
[126.]
M. Vayssairat.
Preventive effect o fan oral prostacyclin analog, beraprost sodium, on digital necrosis in systemic sclerosis French microcirculation society multicenter group for the study of vascular acrosyndromes.
J Rheumatol, 26 (1999), pp. 2173-2178
[127.]
M.D. Mayes.
Endothelin and endothelin receptor antagonists in systemic rheumatic disease.
Arthritis Rheum, 48 (2003), pp. 1190-1199
[128.]
J.H. Korn, M. Mayes, M. Matucci-Cerinic, M. Rainisio, J. Pope, E. Hachulla, et al.
Digital ulcers in systemic sclerosis. Prevention by treatment with bosentan, an oral endothelin receptor antagonist.
Arthritis Rheum, 50 (2004), pp. 3985-3993
[129.]
Seibold JR, Denton CP, Furst DE, Matucci-Cerini M, Mayes MD, Morganti A, et al. Bosentan prevents occurrence but does not speed healing of digital ulcers in patients with systemic sclerosis. ACR 2005 poster presentation.
[130.]
J.J. Alegre-Sancho, J.A. Román-Ivorra, C. Fernández-Carballido, et al.
Efficacy of bosentan in the treatment of unresponsive digital ulcers in patients with systemic sclerosis and other connective tissue diseases Results at 24 weeks.
Ann Rheum Dis, 63 (2004), pp. 339
[131.]
J.J. Alegre-Sancho, N. Fernández-Llanio, R. Hortal-Alonso, S. Muñoz-Gil, J.A. Román-Ivorra, et al.
Long term efficacy and safety of bosentan in the treatment of ischemic digital ulcers due to severe Raynaud's phenomenon in patients with systemic sclerosis.
Ann Rheum Dis, 64 (2005), pp. 287
[132.]
M.J. Zinder, M.R. Jacobs, R.G. Grau, et al.
Resolution of severe digital ulceration during a course of bosentan therapy.
Ann Intern Med, 142 (2005), pp. 802-803
[133.]
M. Humbert, J. Cabane.
Succesful treatment of systemic sclerosis digital ulcers and pulmonary arterial hipertension with endothelin receptor antagonist bosentan.
Rheumatology, 42 (2003), pp. 191-193
[134.]
M. Ramos-Casals, P. Brito-Zerón, N. Nardo, et al.
Successful treatment of severe Raynaud's phenomenon with bosentan in four patients with systemic sclerosis.
Rheumatology, 43 (2004), pp. 1454-1456
[135.]
M.E. Hettema, D. Zhang, H. Bootsma, C.G.M. Kallenberg.
Bosentan therapy for patients with severe Raynaud's phenomenon in systemic sclerosis.
Ann Rheum Dis, 66 (2007), pp. 1398-1399
[136.]
J.J. Alegre-Sancho, J.A. Román Ivorra, et al.
Bosentan therapy for cutaneous fibrosis in systemic sclerosis.
Curr Med Res Opin, 23 (2006), pp. S98
[137.]
J. Gore, R. Silver.
Oral sildenafil for the treatment of Raynaud's phenomenon and digital ulcers secondary to systemic sclerosis.
Ann Rheum Dis, 64 (2005), pp. 1387
[138.]
C.L. Colglazier, P.G. Sutej, K.S. O’Rourke.
Severe refractory fingertip ulcerations in a patient with scleroderma: successful treatment with sildenafil.
J Rheumatol, 32 (2005), pp. 2440
[139.]
J.R. Lichtenstein.
Use of sildenafil citrate in Raynaud's phenomenon: comment on the article by Thompson et al.
Arthritis Rheum, 48 (2003), pp. 282
[140.]
C.R. Kumana, G.T. Cheung, C.S. Lau.
Severe digital ischaemia treated with phosphodiesterase inhibitors.
Ann Rheum Dis, 63 (2004), pp. 1522
[141.]
R. Fries, K. Shariat, H. Von Wilmowsky, M. Bohm.
Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilator therapy.
Circulation, 112 (2005), pp. 2980
[142.]
Y. Kamata, T. Kamimura, M. Iwamoto, S. Minota.
Comparable effects of sildenafil citrate and alprostadil on severe Raynaud's phenomenon in a patient with systemic sclerosis.
Clin Exp Dermatol, 30 (2005), pp. 451
[143.]
Zamiri B, Koman AL, Smith BP, et al. Double-blind placebo- controlled trial of sildenafil for the management of primary Raynaud's phenomenon (abstract ISAT0342). Presentado en el EULAR 2004 (acceso enero de 2005). Disponible en: www.eular.org.
[144.]
E. Caglayan, M. Huntgeburth, T. Karasch, et al.
Phosphodiesterase type 5 inhibition is a novel therapeutic option in Raynaud disease.
Arch Intern Med, 166 (2006), pp. 231
[145.]
B. Coleiro, S.E. Marshall, C.P. Denton, et al.
Treatment of Raynaud's phenomenon with the selective serotonin reup-take inhibitor fluoxetine.
Rheumatology (Oxford), 40 (2001), pp. 1038
[146.]
I.A. Jaffe.
Serotonin reuptake inhibitors in Raynaud's phenomenon.
Lancet, 345 (1995), pp. 1378
[147.]
C. Kan, S. Akimoto, M. Abe, et al.
Preliminary thermographic evaluation of new nitroglycerine tape on the peripheral circulatory disturbance in systemic sclerosis.
Ann Rheum Dis, 61 (2002), pp. 177
[148.]
P. Sambo, D. Amico, R. Giacomelli, M. Matucci-Cerinic, F. Salsano, G. Valentini, et al.
Intravenous N-Acetylcysteine for treatment of Raynaud's secondary to systemic sclerosis: A pilot study.
J Rheumatol, 28 (2001), pp. 2257-2262
[149.]
M. Kuwana, J. Kaburaki, Okazaki, et al.
Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis.
Arthritis Rheum, 54 (2006), pp. 1946
[150.]
H.J. Williams, D.E. Furst, S.L. Dahl, V.D. Steen, C. Marks, E.J. Alpert, et al.
Double-blind, multicenter controlled trial comparing topical dimethyl sulfoxide and normal saline for treatment of hand ulcers in patients with systemic sclerosis.
Arthritis Rheum, 28 (1985), pp. 308-314
[151.]
J. Lukac, J. Rovensky, H. Tauchmannova, D. Zitnan.
Effect of ketanserin on Raynaud's phenomenon in progressive systemic sclerosis: a double blind trial.
Drugs Exp Clin Res, 11 (1985), pp. 659-663
[152.]
J.D. Coffman, D.L. Clement, M.A. Creager, et al.
International study of Ketanserin in Raynaud's phenomenon.
Am J Med, 87 (1989), pp. 264
[153.]
M.L. Ciompi, L. Bazzichi, D. Melchiorre, F. De Giorgio, F. Bondi, L. Puccetti.
A placebo-controlled study on urokinase therapy in systemic sclerosis.
Biomed Pharmacother, 50 (1996), pp. 363
[154.]
R. Jones.
Relaxin (Connetics/Cellthech).
Drugs, 4 (2001), pp. 206-217
[155.]
C.P. Denton, K. Howell, R.J. Stratton, C.M. Black.
Long-term low molecular weight heparin therapy for severe Raynaud's phenomenon: a pilot study.
Clin Exp Rheumatol, 18 (2000), pp. 499
[156.]
V.L. Beckett, D.L. Conn, V. Fuster, et al.
Trial of platelet-inhibiting during in scleroderma. Double-blind study with dipyridamole and aspirin.
Arthritis Rheum, 27 (1984), pp. 1137
[157.]
T. Sycha, M. Graninger, E. Auff, P. Schnider.
Botulinum toxin in the treatment of Raynaud's phenomenon: a pilot study.
Eur J Clin Invest, 34 (2004), pp. 312-313
[158.]
J.L. Morris, P. Jobling, I.L. Gibbins.
Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons.
Am J Physiol Heart Circ Physiol, 281 (2001), pp. H2124-H2132
[159.]
D.S. Ruch, M. Holden, B.P. Smith, T.L. Smith, L.A. Koman.
Periarterial Sympathectomy in scleroderma patients: Intermediate-term follow up.
J Hand Surgery, 27A (2002), pp. 258-264
[160.]
S.V. Kotsis, K.C. Chung.
A systematic review of the outcome of digital sympathectomy for treatment of chronic digital ischemia.
J Rheumatol, 30 (2003), pp. 1788
[161.]
E.R. Bogoch, D.K. Gross.
Surgery of the hand in patients with systemic sclerosis: outcomes and considerations.
J Rheumatol, 32 (2005), pp. 642-648
[162.]
M.H. Taylor, J.A. McFadden, M.B. Bolster, R.M. Silver.
Ulnar artery involvement in systemic sclerosis.
J Rheumatol, 29 (2002), pp. 102
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