Preview

Современная ревматология

Расширенный поиск

Синдром Рейно в практике ревматолога

https://doi.org/10.14412/1996-7012-2014-2-48-57

Аннотация

Синдром Рейно (СР) широко распространен в популяции, преобладает среди женщин и в большинстве случаев дебютирует в возрасте до 30 лет. Впервые синдром описан М. Рейно более 150 лет назад, в дальнейшем был выделен первичный (болезнь Рейно) и вторичный СР. Патофизиология СР до конца неясна, по-видимому, СР является мультифакторным заболеванием. Считается, что причиной чрезмерно выраженного вазоспазма в ответ на провоцирующие стимулы является дефект центральных и локальных механизмов регуляции сосудистого тонуса. Среди этих факторов важными представляются сосудистые эндотелиальные, внутрисосудистые и нейрональные нарушения. Существенную роль в патофизиологии вторичного СР играют структурные изменения сосудов, наблюдаемые при капилляроскопии ногтевого ложа. Диагностика СР предполагает в первую очередь определение его клинического варианта, так как вторичный СР бывает проявлением или предвестником некоторых аутоиммунных, гематологических, эндокринных, неопластических и иных заболеваний. Наиболее часто вторичный СР отмечается у больных с системными ревматическими заболеваниями. Лечение вторичного СР остается неудовлетворительным вследствие неполного представления о патофизиологических механизмах его развития. В настоящее время в лечении СР применяются препараты разных лекарственных групп, включая блокаторы кальциевых каналов, ингибиторы фосфодиэстеразы 5-го типа, антагонисты рецепторов эндотелина и др.

В обзоре рассматриваются вопросы патогенеза, алгоритм ранней и дифференциальной диагностики СР, современные подходы к лечению на основе анализа данных литературы и результатов собственных исследований. 

Об авторе

Р.Т. Алекперов
ФГБУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» РАМН, Москва, Россия


Литература

1. Raynaud M. Local Asphyxia and Symmetrical Gangrene of the Extremities. London: New Sydenham Society; 1862.

2. Lewis T. Experiments relating to the peripheral mechanisms involved in spasmodic arrest of the circulation in the fingers, a variety of Raynaud’s disease. Heart. 1929;15:7–101.

3. Maricq HR, Carpentier, PH, Weinrich, MC, et al. Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region comparison. J Rheumatol. 1997;24(5):879–89.

4. Harada N, Ueda A, Takegata S. Prevalence of Raynaud's phenomenon in Japanese males and females. J Clin Epidemiol. 1991;44(7):649–55. DOI: http://dx.doi.org/10.1016/0895-4356(91)90026-6

5. Voulgari PV, Alamanos Y, Papazisi D, Christou K, et al. Prevalence of Raynaud's phenomenon in a healthy Greek population. Ann Rheum Dis. 2000;59(3):206–10. DOI: http://dx.doi.org/10.1136/ard.59.3.206.

6. Riera G, Vilardell M, Vaque J, et al. Prevalence of Raynaud’s phenomenon in a healthy Spanish population. J Rheumatol. 1993;20(1):66–9.

7. Bakst R, Merola JF, Franks AG Jr, Sanchez M. Raynaud’s phenomenon: pathogenesis and management. J Am Acad Dermatol. 2008;59(4):633–53. DOI: http://dx.doi.org/10.1016/j.jaad.2008.06.004.

8. Kaheleh B, Matucci-Cerinic M. Raynaud’s phenomenon and scleroderma. Dysregulated neuroendothelial control of vascular tone. Arthritis Rheum. 1995;38(1):1–4. DOI: http://dx.doi.org/10.1002/art.1780380102.

9. Rajagopalan S, Pfenninger D, Kehrer C, et al. Increased asymmetric dimethylarginine and endothelin 1 levels in secondary Raynaud's phenomenon: implications for vascular dysfunction and progression of disease. Arthritis Rheum. 2003;48(7):1992–2000. DOI: http://dx.doi.org/10.1002/art.11060.

10. Kirchengast M, Munter K. Endothelin-1 and endothelin receptor antagonists in cardiovascular remodeling. Proc Soc Exp Biol Med. 1999;221(4):312–25. DOI: http://dx.doi.org/10.3181/00379727-221-44414.

11. Furspan PB, Chatterjee S, Freedman RR. Increased tyrosine phosphorylation mediates the cooling-induced contraction and increased vascular reactivity of Raynaud’s disease. Arthritis Rheum. 2004;50(5):1578–85. DOI: http://dx.doi.org/10.1002/art.20214.

12. Chotani MA, Flavahan S, Mitra S, et al. Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous

13. arteries. Am J Physiol. 2000;278(4):H1075–83.

14. Bailey SR, Eid AH, Mitra S, et al. Rho-kinase mediates cold-induced constriction of cutaneous arteries: role of alpha2c-adrenoceptor translocation. Circ Res. 2004;94(10):1367–74. DOI: http://dx.doi.org/10.1161/01.RES.000012840 7.45014.58.

15. Bailey SR, Mitra S, Flavahan S, Flavahan NA. Reactive oxygen species from smooth muscle mitochondria initiate cold-induced constriction of cutaneous arteries. Am J Physiol. 2005;289(1):H243–50.

16. Cooke JP, Marshall JM. Mechanisms of Raynaud’s disease. Vasc Med. 2005;10(4):293–307. DOI: http://dx.doi.org/10.1191/1358863x05vm639ra.

17. LeRoy EC, Medsger TR. Raynaud’s phenomenon: a proposal for classification. Clin Exp Rheumatol. 1992;10(5):485–8.

18. Kallenberg CG. Early detection of connective tissue disease in patients with Raynaud’s phenomenon. Rheum Dis Clin North Am. 1990;16(1):11–30.

19. De Angelis R, Salaffi F, Grassi W. Raynaud's phenomenon: prevalence in an Italian population sample. Clin Rheumatol. 2006;25(4):506–10. DOI: http://dx.doi.org/10.1007/s10067-005-0077-1.

20. 19. Maricq HR, Weinrich MC, Keil JE, et al. Prevalence of scleroderma spectrum disorders in the general population of South Carolina. Arhritis Rheum. 1989;32(8):998–1006. DOI: http://dx.doi.org/10.1002/anr.1780320809.

21. Palmer K, Griffin M, Syddall H, et al. Prevalence of Raynaud's phenomenon in Great Britain and its relation to hand transmitted vibration: a national postal survey. Occup Environ Med. 2000 July;57(7):448–52. DOI: http://dx.doi.org/ 10.1136/oem.57.7.448.

22. Brennan P, Silman A, Black C, et al. Validity and reliability of three methods used in the diagnosis of Raynaud’s phenomenon. The UK Scleroderma Study Group. Br J Rheumatol. 1993;32(5):357–61. DOI: http://dx.doi.org/10.1093/rheumatology/32.5.357.

23. Raynaud’s Treatment Study Investigatirs. Comparison of sustained-release nifedipine and temperature biofeedback for treatment of primary Raynaud phenomenon. Results from a randomized clinical trial with 1-year follow-up. Arch Intern Med. 2000;160(8):1101–8. DOI: http://dx.doi.org/10.1001/archinte.160.8.1101.

24. Planchon B, Pistorius MA, Beurrier P, De Faucal P. Primary Raynaud's phenomenon. Age of onset and pathogenesis in

25. a prospective study of 424 patients. Angiology. 1994;45(8):677–86. DOI: http://dx.doi.org/10.1177/000331979404500802.

26. Freedman RR, Mayes MD. Familial aggregation of primary Raynaud’s disease. Arthritis Rheum. 1996;39(7):1189-91. DOI: http://dx.doi.org/10.1002/art.1780390717.

27. Herrick AL, Clark S. Quantifying digital vascular disease in patients with primary Raynaud's phenomenon and systemic sclerosis. Ann Rheum Dis. 1998;57(2):70–8. DOI: http://dx.doi.org/10.1136/ard.57.2.70.

28. Anderson ME, Moore TL, Lunt M, Herrick AL. The «distal-dorsal difference»: a thermographic parameter by which to differentiate between primary and secondary Raynaud's phenomenon. Rheumatology (Oxford). 2007;46(3):533–8. DOI: http://dx.doi.org/10.1093/rheumatology/kel3 30. Epub 2006 Oct 2.

29. Keberle M, Tony HP, Jahns R, et al. Assessment of microvascular changes in Raynaud’s phenomenon and connective tissue disease using colour doppler ultrasound. Rhematology (Oxford). 2000;39(11):1206–13. DOI: http://dx.doi.org/10.1093/rheumatology/39.11.1206.

30. Gifford RW Jr, Hines EA Jr. Raynaud’s disease among women and girls. Circulation. 1957;16(6):1012–21. DOI: http://dx.doi.org/10.1161/01.CIR.16.6.1012.

31. DeAngelis R, Del Medico P, Blasetti P, Cervini C. Raynaud's phenomenon: clinical spectrum of 118 patients. Clin Rheumatol. 2003;22(4–5):279–84. DOI: http://dx.doi.org/10.1007/s10067-003-0726-1.

32. Ziegler S, Brunner M, Eigenbauer E, Minar E. Long-term outcome of primary Raynaud's phenomenon and its conversion to connective tissue disease: a 12-year retrospective patient analysis. Scand J Rheumatol. 2003;32(6):343–7. DOI: http://dx.doi.org/10.1080/03009740410005007.

33. Spencer-Green G. Outcomes in primary Raynaud phenomenon: a meta-analysis of the frequency, rates, and predictors of transition to secondary diseases. Arch Intern Med. 1998;158(6):595–600. DOI: http://dx.doi.org/10.1001/archinte.158.6.595.

34. Thompson AE, Pope JE. Calcium channel blockers for primary Raynaud’s phenomenon: a meta-analysis. Rheumatology (Oxford). 2005;44(2):145–50. DOI: http://dx.doi.org/ 10.1093/rheumatology/keh390.

35. Werner C, Baumhakel M, Teo KK, et al. RAS blockade with ARB and ACE inhibitors: current perspective on rationale and patient selection. Clin Res Cardiol. 2008;97(7):418–31. DOI: http://dx.doi.org/10.1007/s00392-008-0668-3.

36. Garcia-Carrasco M, Jimenez-Hernandez M, Escarcega RO, et al. Treatment of Raynaud’s phenomenon. Autoimmunity reviews. 2008;8(1):62–8. DOI: http://dx.doi.org/10.1016/j.autrev.2008.07.002.

37. Dziadzio M, Denton CP, Smith R, et al. Losartan therapy for Raynaud’s phenomenon and scleroderma. Arthritis Rheum. 1999;42(12):2646–55. DOI: http://dx.doi.org/10.1002/1529-0131(199912)42:12%3C2646::AID-ANR21%3E3.0.CO;2-T.

38. Wigley FM, Wise RA, Seibold JR, et al. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med. 1994;120(3):199–206. DOI: http://dx.doi.org/10.7326/0003-4819-120-3-199402010-00004.

39. Pope J, Fenlon D, Thompson A, et al. Iloprost and cisaprost for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev. 1998;(2):CD000953.

40. Colaci M, Sebastiani M, Giuggioli D, et al. Cardiovascular risk and prostanoids in SSc. Clin Exp Rheumatol. 2008;26(2):333–6.

41. Kawald A, Burmester GR, Huscher D, et al. Low versus high-dose iloprost therapy over 21 days in patients with secondary Raynaud’s phenomenon and systemic sclerosis: a randomized, open, single-center study. J Rheumatol. 2008;35(9):1830–7.

42. Алекперов РТ. Силденафил в лечении синдрома Рейно. Научно-практическая ревматология. 2009;48(3):38–45. [Alekperov RT. Sildenafil in the treatment of Raynaud’s syndrome. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2009;48(3):38–45. (In Russ.)]. DOI: http://dx.doi.org/10.14412/1995-4484-2009-1311.

43. Fries R, Shariat K, von Wilmowsky H, Bohm M. Sildenafil in the treatment of Raynaud’s phenomenon resistant to vasodilatory therapy. Circulation. 2005;112(19):2980–5.

44. Pakozdi A, Howell K, Black CM, Denton CP. Addition of the short term phosphodiesterase-5 inhibitor sildenafil to iloprost therapy for scleroderma digital vasculopathy [abstract]. ACR/ARHP Scientific Meeting 2007. Boston, MA: November 6–11, 2007; abstract 2167.

45. Becker M, Bruckner CS, Scherer H, et al. Effect of sildenafil on digital ulcers in systemic sclerosis – analysis from a single centre pilot study. Ann Rheum Dis. 2010 Aug;69(8):1475–8. DOI: 10.1136/ard.2009.116475. Epub 2009 Nov 8.

46. Brueckner C, Scherer U, Burmester G, et al. Effect of sildenafil on healing of digital ulcers in patients with systemic sclerosis [abstract]. Ann Rheum Dis. 2008;67 (Suppl 2):362.

47. Shenoy P, Agarwal V, Kumar S, et al. Efficacy of tadalafil in secondary Raynaud’s phenomenon resistant to vasodilator therapy: a doubleblind randomized cross-over trial [abstract]. Arthritis Rheum. 2008;58(9 Suppl):S402.

48. Zamiri B, Koman AL, Smith BP, et al. Double-blind, placebo-controlled trial of sildenafil for the management of primary Raynaud’s phenomenon [abstract]. Ann Rheum Dis. 2004;63(Suppl. 1):484–5.

49. Schiopu E, Hsu VM, Impens AJ, Rothman JA, et al. Randomized placbo-controlled crossover trial of tadalafil in Raynaud’s phenomenon secondary to systemic sclerosis. J Rheumatol. 2009;36(10):2264–8. DOI: 10.3899/jrheum.090270. Epub 2009 Sep 15. 48. Man Tsuey Tse. Trial watch: Phase III success for first-in-class pulmonary hypertension drug. Nature Reviews Drug. 2012;11(12):896. DOI: 10.1038/nrd3906.

50. Алекперов РТ, Ананьева ЛП, Корзенева ЕГ, Черемухина ЕО. Эффективность и безопасность силденафила у больных системной склеродермией. Терапевтический архив. 2013;85(5):60–7. [Alekperov RT, Anan'eva LP, Korzeneva EG,

51. Cheremukhina EO. Efficacy and safety of sildenafil in patients with systemic scleroderma. Terapevticheskii arkhiv. 2013;85(5):60–7. (In Russ.)]

52. Teh LS, Manning J, Moore T, et al. Sustained-release transdermal glyceryl trinitrate patches as a treatment for primary and secondary Raynaud’s phenomenon. Br J Rheumatol. 1995;34(7):636–41. DOI: http://dx.doi.org/10.1093/rheumatology/34.7.636.

53. Franks AG. Topical glyceryl trinitrate as adjunctive treatment in Raynaud’s disease. Lancet. 1982;1(8263):76–7. DOI: http://dx.doi.org/10.1016/S0140-6736(82)90215-X.

54. Chung L, Shapiro L, Fiorentino D, et al. MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: A randomized, controlled trial. Arthritis Rheum. 2009;60(3):870–7. DOI: http://dx.doi.org/10.1002/art.24351.

55. Morelli S, Ferri C, Polettini E, et al. Plasma endothelin-1 levels, pulmonary hypertension and lung fibrosis in patients with systemic sclerosis. Am J Med. 1995;99(3):255–60. DOI: http://dx.doi.org/10.1016/S0002-9343(99)80157-0.

56. Korn JH, Mayes M, Matucci Cerinic M, et al. Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum. 2004;50(12):3985–93. DOI: http://dx.doi.org/10.1002/art.20676.

57. Black C, Denton CP, Furst DE, et al. Bosentan reduces the number of new digital ulcers in patients with systemic sclerosis – open label extension to a double-blind trial [abstract]. Ann Rheum Dis. 2006;65 (Suppl 2):384.

58. Seibold JR, Denton CP, Furst DE, et al. Bosentan prevents occurrence but does not speed healing of digital ulcers in patients with systemic sclerosis (SSc) [abstract]. Annual Meeting of the American College of Rheumatology 2005; abstract L2.

59. Garcia de la Pena-Lefebvre P, Rubio SR, Exposito MV, et al. Long-term experience of bosentan for treating ulcers and healed ulcers in systemic sclerosis patients. Rheumatology (Oxford). 2008;47(4):464–6. DOI: 10.1093/rheumatology/ken001. Epub 2008 Feb 7.

60. Launay D, Diot E, Pasquier E, et al. Bosentann for treatment of active digital ulcers in patients with systemic sclerosis (9 cases). Presse Med. 2006;35(4 Pt 1):587–92. DOI: http://dx.doi.org/10.1016/S0755-4982(06)74645-0.

61. Selenko-Gebauer N, Duschek N, Minimair G, et al. Successful treatment of patients with severe secondary Raynaud’s phenomenon with the endothelial receptor antagonist bosentan. Rheumatology (Oxford). 2006;45:iii45–8. DOI: http://dx.doi.org/10.1093/rheumatology/kel290.

62. Funauchi M, Kishimoto K, Shimazu H, et al. Effects of bosentan on the skin lesions: an observational study from a single center in Japan. Rheumatol Int. 2009;29(7):769–75. DOI: 10.1007/s00296-008-0789-z.

63. Epub 2008 Nov 27.

64. Hettema ME, Zhang D, Bootsma H, Kallenberg CGM. Bosentan therapy for patients with severe Raynaud’s phenomenon in systemic sclerosis [letter]. Ann Rheum Dis. 2007;66(10):1398–9. DOI: http://dx.doi.org/10.1136/ard.2007.073684.

65. Ramos-Casals M, Brito-Zeron P, Nardi N, et al. Successful treatment of severe Raynaud’s phenomenon with bosentan in four patients with systemic sclerosis. Rheumatology (Oxford). 2004;43(11):1454–6. DOI: http://dx.doi.org/10.1093/rheumatology/keh340.

66. Dunne J, Dutz J, Shojania K, et al. Treatment of severe Raynaud’s phenomenon with bosentan in a patient with systemic sclerosis. Rheumatology (Oxford). 2006;45(7):911–2. DOI: http://dx.doi.org/10.1093/rheumatology/kei129. 64. Moore TL, Vail A, Herrick AL. Assessment of digital vascular structure and function in response to bosentan in patients with systemic sclerosis-related Raynaud’s phenomenon. Rheumatology (Oxford). 2007;46(2):363–4. DOI: http://dx.doi.org/10.1093/rheumatology/kel3 83. Epub 2006 Nov 20.

67. Pope J, Fenlon D, Thompson A, et al. Prazosin for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev. 2000;(2):CD000956.

68. Bolte MA, Avery D. Case of fluoxetineinduced remission of Raynaud’s phenomenon – a case report. Angiology. 1993;44(2):161–3. DOI: http://dx.doi.org/10.1177/ 000331979304400213.

69. Rey J, Cretel E, Jean R, et al. Serotonin reuptake inhibitors, Raynaud’s phenomenon and erythromelalgia. Rheumatology (Oxford). 2003;42(4):601–2. DOI: http://dx.doi.org/ 10.1093/rheumatology/keg137.

70. Buecking A, Rougemont E, Zullino DF. Treatment of Raynaud’s phenomenon with escitalopram. Int J Neuropsychopharmacol. 2005;8(2):307–308. DOI: http://dx.doi.org/10.1017/S1461145704004882. Epub 2004 Nov 30.

71. Kato S, Kishiro I, Machida M, et al. Suppressive effect of sarpogrelate hydrochloride on respiratory failure and right ventricular failure with pulmonary hypertension in patients with systemic sclerosis. J Int Med Res. 2000;28(6):258–68. DOI: http://dx.doi.org/10.1177/147323000002800602. 70. Yoshimasu T, Ikeda T, Uede K, et al. Effects of sarpogrelate hydrochloride on skin ulcers and quality of life in patients with systemic sclerosis. J Dermatol. 2012;39(6):536–40. DOI: http://dx.doi.org/10.1111/j.1346- 8138.2011.01432.x.

72. Pope J, Fenlon D, Thompson A, et al. Ketanserin for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev. 2000;(2):CD000954.

73. Алекперов РТ, Корзенёва ЕГ, Александрова ЕН и др. Плейотропные эффекты статинов при системной склеродермии. Терапевтический архив. 2011;83(5):41–7. [Alekperov RT, Korzeneva EG, Alexandrova EN, et al. Pleiotropic effects of statins in systemic sclerosis. Terapevticheskii arkhiv. 2011;83(5):41–7. (In Russ.)]

74. Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol. 2008;35(9):1801–8. Epub 2008 Aug 15.

75. Malenfant D, Catton M, Pope JE. The efficacy of complementary and alternative medicine in the treatment of Raynaud's phenomenon: a literature review and meta-analysis. Rheumatology (Oxford). 2009;48(7):791–5. DOI: http://dx.doi.org/ 10.1093/rheumatology/kep039.

76. Baumhä kel M, Bö hm M. Recent achievements in the management of Raynaud’s phenomenon. Vasc Health Risk Manag. 2010;6:207–14. DOI: http://dx.doi.org/10.2147/VHRM.S5255.


Рецензия

Просмотров: 2665


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1996-7012 (Print)
ISSN 2310-158X (Online)