硬皮病治疗研究进展及治疗指南演变
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摘要
硬皮病是一组以增厚硬化的皮肤病变为共同表现的自身免疫性疾病,受累组织和器官广泛,多种发病机制参与其中。目前,硬皮病的治疗缺乏明确有效的药物,多以免疫抑制、抗纤维化及对症支持治疗为主,近年来一些针对血管病变的新药物及生物制剂在硬皮病中逐渐得到应用,为硬皮病的治疗提供了新的机遇。对于硬皮病的治疗推荐,近年来也有不断的更新和完善,有利于硬皮病的早期评估及系统治疗。
Scleroderma is a group of autoimmune diseases characterized by thickening and hardening of skin lesions. It involves a wide range of tissues and organs, and various mechanisms of pathogenesis. At present, drugs with established effects are lacking for the treatment of scleroderma. Immunosuppression, anti-fibrosis and symptomatic supportive therapy are often used in the treatment of scleroderma. Recently,some new drugs for vascular diseases and some biological agents have been gradually applied in scleroderma, providing new opportunities for treatment. The guidelines for the treatment of scleroderma has also been constantly updated and improved in recent years, which is conducive to the early evaluation and systematic treatment of scleroderma.
Scleroderma is a group of autoimmune diseases characterized by thickening and hardening of skin lesions. It involves a wide range of tissues and organs, and various mechanisms of pathogenesis. At present, drugs with established effects are lacking for the treatment of scleroderma. Immunosuppression, anti-fibrosis and symptomatic supportive therapy are often used in the treatment of scleroderma. Recently,some new drugs for vascular diseases and some biological agents have been gradually applied in scleroderma, providing new opportunities for treatment. The guidelines for the treatment of scleroderma has also been constantly updated and improved in recent years, which is conducive to the early evaluation and systematic treatment of scleroderma.
引文
[1]林果为,王吉耀,葛均波.实用内科学[M].15版.北京:人民卫生出版社,2017.
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[47]Andersen B N,Johansen P B,Abrahamsen B.Proton pump inhibitors and osteoporosis[J].Curr Opin Rheumatol,2016,28(4):420-425.
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[50]Guillaume-Jugnot P,Badoglio M,Labopin M,et al.Autologous haematopoietic stem cell transplantation(AHSCT)in autoimmune disease adult patients in France:analysis of the long-term outcome from the French Society for Bone Marrow Transplantation and Cellular Therapy(SFGM-TC)[J/OL].Clin Rheumatol,2019[2019-02-21].https://doi.org/10.1007/s10067-019-04435-2.
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[2]Hochberg M C,Gravallese E M,Silman A J,et al.Rheumatology[M].7th edition.Amsterdam:Elsevier,2018.
[3]Van den Hoogen F H,Boerbooms A M,Swaak A J,et al.Comparison of methotrexate with placebo in the treatment of systemic sclerosis:a 24 week randomized double-blind trial,followed by a 24 week observational trial[J].Br J Rheumatol,1996,35(4):364-372.
[4]Pope J E,Bellamy N,Seibold J R,et al.A randomized,controlled trial of methotrexate versus placebo in early diffuse scleroderma[J].Arthritis Rheum,2001,44(6):1351-1358.
[5]Dheda K,Lalloo U G,Cassim B,et al.Experience with azathioprine in systemic sclerosis associated with interstitial lung disease[J].Clin Rheumatol,2004,23(4):306-309.
[6]Maas D,Schramm A,Jackle B,et al.Progressive systemic sclerosislong-term treatment with azathioprin(author’s transl)[J].Immun Infekt,1979,7(5):165-169.
[7]Nadashkevich O,Davis P,Fritzler M,et al.A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis[J].Clin Rheumatol,2006,25(2):205-212.
[8]Paone C,Chiarolanza I,Cuomo G,et al.Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy[J].Clin Exp Rheumatol,2007,25(4):613-616.
[9]Clements P J,Lachenbruch P A,Sterz M,et al.Cyclosporine in systemic sclerosis.Results of a forty-eight-week open safety study in ten patients[J].Arthritis Rheum,1993,36(1):75-83.
[10]Giacomelli R,Valentini G,Salsano F,et al.Cyclophosphamide pulse regimen in the treatment of alveolitis in systemic sclerosis[J].JRheumatol,2002,29(4):731-736.
[11]Tashkin D P,Elashoff R,Clements P J,et al.Cyclophosphamide versus placebo in scleroderma lung disease[J].N Engl J Med,2006,354(25):2655-2666.
[12]Tashkin D P,Elashoff R,Clements P J,et al.Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease[J].Am J Respir Crit Care Med,2007,176(10):1026-1034.
[13]Vanthuyne M,Blockmans D,Westhovens R,et al.A pilot study of mycophenolate mofetil combined to intravenous methylprednisolone pulses and oral low-dose glucocorticoids in severe early systemic sclerosis[J].Clin Exp Rheumatol,2007,25(2):287-292.
[14]Tashkin D P,Roth M D,Clements P J,et al.Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease(SLS II):a randomised controlled,double-blind,parallel group trial[J].Lancet Respir Med,2016,4(9):708-719.
[15]Thompson A E,Pope J E.Calcium channel blockers for primary Raynaud’s phenomenon:a meta-analysis[J].Rheumatology(Oxford),2005,44(2):145-150.
[16]Thompson A E,Shea B,Welch V,et al.Calcium-channel blockers for Raynaud’s phenomenon in systemic sclerosis[J].Arthritis Rheum,2001,44(8):1841-1847.
[17]Pope J,Fenlon D,Thompson A,et al.Prazosin for Raynaud’s phenomenon in progressive systemic sclerosis[J/OL].Cochrane Database Syst Rev,2000(2):CD000956[2019-02-21].https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000956/full.
[18]Gliddon A E,Dore C J,Black C M,et al.Prevention of vascular damage in scleroderma and autoimmune Raynaud’s phenomenon:a multicenter,randomized,double-blind,placebo-controlled trial of the angiotensin-converting enzyme inhibitor quinapril[J].Arthritis Rheum,2007,56(11):3837-3846.
[19]Dziadzio M,Denton C P,Smith R,et al.Losartan therapy for Raynaud’s phenomenon and scleroderma:clinical and biochemical findings in a fifteen-week,randomized,parallel-group,controlled trial[J].Arthritis Rheum,1999,42(12):2646-2655.
[20]Coleiro B,Marshall S E,Denton C P,et al.Treatment of Raynaud’s phenomenon with the selective serotonin reuptake inhibitor fluoxetine[J].Rheumatology(Oxford),2001,40(9):1038-1043.
[21]Hummers L K,Dugowson C E,Dechow F J,et al.A multi-centre,blinded,randomised,placebo-controlled,laboratory-based study of MQX-503,a novel topical gel formulation of nitroglycerine,in patients with Raynaud phenomenon[J].Ann Rheum Dis,2013,72(12):1962-1967.
[22]Levien T L.Phosphodiesterase inhibitors in Raynaud’s phenomenon[J].Ann Pharmacother,2006,40(7/8):1388-1393.
[23]Shenoy P D,Kumar S,Jha L K,et al.Efficacy of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilator therapy:a double-blind randomized cross-over trial[J].Rheumatology(Oxford),2010,49(12):2420-2428.
[24]Khanna D,Denton C P,Merkel P A,et al.Effect of macitentan on the development of new ischemic digital ulcers in patients with systemic sclerosis:DUAL-1 and DUAL-2 randomized clinical trials[J].JAMA,2016,315(18):1975-1988.
[25]Timar O,Szekanecz Z,Kerekes G,et al.Rosuvastatin improves impaired endothelial function,lowers high sensitivity CRP,complement and immuncomplex production in patients with systemic sclerosisa prospective case-series study[J/OL].Arthritis Res Ther,2013,15(5):R105[2019-02-21].http://doi.org/10.1186/ar4285.
[26]Launay D,Humbert M,Berezne A,et al.Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease[J].Chest,2011,140(4):1016-1024.
[27]Steen V,Medsger T J.Predictors of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement[J].Arthritis Rheum,2003,48(2):516-522.
[28]Fischer A,Bull T M,Steen V D.Practical approach to screening for scleroderma-associated pulmonary arterial hypertension[J].Arthritis Care Res(Hoboken),2012,64(3):303-310.
[29]Galie N,Barbera J A,Frost A E,et al.Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension[J].N Engl J Med,2015,373(9):834-844.
[30]Hassoun P M,Zamanian R T,Damico R,et al.Ambrisentan and tadalafil up-front combination therapy in scleroderma-associated pulmonary arterial hypertension[J].Am J Respir Crit Care Med,2015,192(9):1102-1110.
[31]Rangarajan V,Matiasz R,Freed B H.Cardiac complications of systemic sclerosis and management:recent progress[J].Curr Opin Rheumatol,2017,29(6):574-584.
[32]Lacroix D,Brigadeau F,Marquie C,et al.Electroanatomic mapping and ablation of ventricular tachycardia associated with systemic sclerosis[J].Europace,2004,6(4):336-342.
[33]Hoffmann-Vold A M,Midtvedt O,Tennoe A H,et al.Cardiopulmonary disease development in anti-RNA polymerase III-positive systemic sclerosis:comparative analyses from an unselected,prospective patient cohort[J].J Rheumatol,2017,44(4):459-465.
[34]Herrick A L,Pan X,Peytrignet S,et al.Treatment outcome in early diffuse cutaneous systemic sclerosis:the European Scleroderma Observational Study(ESOS)[J].Ann Rheum Dis,2017,76(7):1207-1218.
[35]Filaci G,Cutolo M,Scudeletti M,et al.Cyclosporin A and iloprost treatment of systemic sclerosis:clinical results and interleukin-6 serum changes after 12 months of therapy[J].Rheumatology(Oxford),1999,38(10):992-996.
[36]Konma J,Kotani T,Shoda T,et al.Efficacy and safety of combination therapy with prednisolone and oral tacrolimus for progressive interstitial pneumonia with systemic sclerosis:a retrospective study[J].Mod Rheumatol,2018,28(6):1009-1015.
[37]Khanna D,Clements P J,Furst D E,et al.Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement:a randomized,double-blind,placebo-controlled trial[J].Arthritis Rheum,2009,60(4):1102-1111.
[38]Gomes J P,Santos L,Shoenfeld Y.Intravenous immunoglobulin(IVIG)in the vanguard therapy of systemic sclerosis[J/OL].Clin Immunol,2019,199:25-28[2019-02-21].https://www.sciencedirect.com/science/article/pii/S1521661618307149?via%3Dihub.Doi:10.1016/j.clim.2018.12.006.
[39]Daoussis D,Melissaropoulos K,Sakellaropoulos G,et al.A multicenter,open-label,comparative study of B-cell depletion therapy with Rituximab for systemic sclerosis-associated interstitial lung disease[J].Semin Arthritis Rheum,2017,46(5):625-631.
[40]Zhang Y,Liang R,Chen C W,et al.JAK1-dependent transphosphorylation of JAK2 limits the antifibrotic effects of selective JAK2 inhibitors on long-term treatment[J].Ann Rheum Dis,2017,76(8):1467-1475.
[41]Dees C,Tomcik M,Palumbo-Zerr K,et al.JAK-2 as a novel mediator of the profibrotic effects of transforming growth factor beta in systemic sclerosis[J].Arthritis Rheum,2012,64(9):3006-3015.
[42]Khanna D,Denton C P,Jahreis A,et al.Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis(faSScinate):a phase 2,randomised,controlled trial[J].Lancet,2016,387(10038):2630-2640.
[43]Khanna D,Denton C P,Lin C,et al.Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis:results from the open-label period of a phase II randomised controlled trial(faSScinate)[J].Ann Rheum Dis,2018,77(2):212-220.
[44]Odler B,Foris V,Gungl A,et al.Biomarkers for pulmonary vascular remodeling in systemic sclerosis:a pathophysiological approach[J/OL].Front Physiol,2018,9:587[2019-02-21].http://www.frontiersin.org/articles/10.3389/fphys.2018.00587/pdf.
[45]Liaskos C,Marou E,Simopoulou T,et al.Disease-related autoantibody profile in patients with systemic sclerosis[J].Autoimmunity,2017,50(7):414-421.
[46]Bogatkevich G S,Ludwicka-Bradley A,Silver R M.Dabigatran,a direct thrombin inhibitor,demonstrates antifibrotic effects on lung fibroblasts[J].Arthritis Rheum,2009,60(11):3455-3464.
[47]Andersen B N,Johansen P B,Abrahamsen B.Proton pump inhibitors and osteoporosis[J].Curr Opin Rheumatol,2016,28(4):420-425.
[48]Gomm W,von Holt K,Thome F,et al.Association of proton pump inhibitors with risk of dementia:a pharmacoepidemiological claims data analysis[J].JAMA Neurol,2016,73(4):410-416.
[49]Lazarus B,Chen Y,Wilson F P,et al.Proton pump inhibitor use and the risk of chronic kidney disease[J].JAMA Intern Med,2016,176(2):238-246.
[50]Guillaume-Jugnot P,Badoglio M,Labopin M,et al.Autologous haematopoietic stem cell transplantation(AHSCT)in autoimmune disease adult patients in France:analysis of the long-term outcome from the French Society for Bone Marrow Transplantation and Cellular Therapy(SFGM-TC)[J/OL].Clin Rheumatol,2019[2019-02-21].https://doi.org/10.1007/s10067-019-04435-2.
[51]Del P N,Pignataro F,Zaccara E,et al.Autologous hematopoietic stem cell transplantation for treatment of systemic sclerosis[J/OL].Front Immunol,2018,9:2390[2019-02-21].https://www.frontiersin.org/articles/10.3389/fimmu.2018.02390/full.
[52]Granel B,Daumas A,Jouve E,et al.Safety,tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis:an open-label phase I trial[J].Ann Rheum Dis,2015,74(12):2175-2182.
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