rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2004-796rsp-933Research ArticleСтатьиArticlesКлинико-иммунологические проявления первичного и вторичного антифосфолипидного синдромаClinical and immunological features of primary and secondary antiphospholipid syndromeReshetnvakT MReshetnvakT M-KotelnikovaT NKotelnikovaT N-KalashnikovaL AKalashnikovaL A-ЛисицынаТ. А.LisitsynaT A-AlexandrovaE NAlexandrovaE N-MachE SMachE S-TihonovaT LTihonovaT L-АлекбероваЗемфира СадуллаевнаAlekberovaZ S-NassonovaV ANassonovaV A-ВолковА. В.VolkovA. V.-NassonovaV ANassonovaV A-NassonovE LNassonovE L-200415082004424№4 (2004)1523Copyright © Reshetnvak T.M., Kotelnikova T.N., Kalashnikova L.A., Лисицына Т.А., Alexandrova E.N., Mach E.S., Tihonova T.L., Алекберова З.С., Nassonova V.A., Волков А.В., Nassonova V.A., Nassonov E.L., 20042004Reshetnvak T.M., Kotelnikova T.N., Kalashnikova L.A., Лисицына Т.А., Alexandrova E.N., Mach E.S., Tihonova T.L., Алекберова З.С., Nassonova V.A., Волков А.В., Nassonova V.A., Nassonov E.L.Reshetnvak T.M., Kotelnikova T.N., Kalashnikova L.A., Lisitsyna T.A., Alexandrova E.N., Mach E.S., Tihonova T.L., Alekberova Z.S., Nassonova V.A., Volkov A.V., Nassonova V.A., Nassonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/933

Цель. Ретроспективный анализ клинико-лабораторных признаков дебюта болезни и клинических проявлений на момент обследования у больных первичным антифосфолипидным синдромом (ПАФС) и вторичным АФС на фоне системной красной волчанки (СКВ) Материал и методы. 280 (184 жен и 96 муж) больных СКВ и 84 (60 жен и 24 муж) пациента с ПАФС были включены в исследование. 142 из 280 больных СКВ имели АФС. Возраст больных СКВ на момент исследования составлял 31,2+11,1 лет и длительность заболевания 8,6+7,2 лет. Средний возраст больных ПАФС был 35,6±9,9 лет и длительность заболевания - 11,9±8,5 лет. Для верификации сосудистых осложнений проводились УЗДГ периферических сосудов, ЭхоКГ, УЗИ органов брюшной полости, при необходимости компьтерная томография головного мозга, грудной клетки, брюшной полости. Серологическими маркерами АФС являлись антикардиоли- пиновые антитела (аКЛ) и волчаночный антикоагулянт (ВА). Результаты. У 75% из 280 больных заболевание дебютировало с признаков СКВ, в 17% - с симптомов АФС и в 8% - с тромбоцитолении. У 5 из 138 больных СКВ без АФС отмечено появление аФЛ и клинических признаков АФС в процессе наблюдения. Начало заболевания с какого-либо признака СКВ при вторичном АФС определялось у 54% из 142 больных, с АФС - у 34% и с тромбоцитопении - у 12% пациентов. Тромбоцитопения в дебюте при ПАФС встречалась намного реже: у 5 из 84 больных, у остальных - в дебюте отмечались признаки АФС. У 8 пациентов наблюдалась трансформация ПАФС в СКВ. Частота тромботических осложнений в целом среди больных СКВ составила 42%, Достоверно чаше они выявлялись АФС, как при вторичном (СКВ+АФС), так и ПАФС - у 76% (108 из 142) и 90% (76 из 84) больных соответственно, против 6% (8 из 138) при СКВ без АФС (р< 0,0001). Выявлена ассоциация пороков сердца с АФС. Пороки сердца были обнаружены у 43% больных с ПАФС, у 27 % - с СКВ+АФС и только у 2% больных СКВ без АФС. Спектр неврологических проявлений ПАФС и СКВ+АФС был схож, но НМ К при ПАФС выявлялись достоверно чаще: у 46% (44 из 84) больных против 26% из 142 пациентов СКВ+АФС. Для ПАФС не было характерным развитие дигитальных некрозов, инфарктов ногтевого ложа, пурпуры, в генезе которых, по-виднмому, участвует воспаление. Заключение. Наши данные продемонстрировали трудность верифнкаци ПАФС, возможность его трансформации во вторичный, что требует динамического клинико-лабораторного наблюдения за этой категорией больных. Кроме того, несмотря на схожесть двух форм АФС выявлены некоторые отличительные признаки первичного и вторичного АФС.

Objective. Rertrospective analysis of clinical and laboratory features of primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in systemic lupus erythematosus (SLE). Material and methods. 280 pts (96 male, 184 female) with SLE were included. 142 had SAPS and 84 (24 male, 60 female) - PAPS. Mean age was 31,2±ll,l years and mean disease duration - 8.6+7,2 years. PAPS pts mean age was 35,6±9,9 years and mean disease duration - 1 1,9±8,5 years. Peripheral vessels USDG and echocardiography (EchoCG) were performed to verify vascular complications. Anticardiolipin antibodies (АСА) and lupus anticoagulant (LA) served as serological markers of APS. Results. In 75% of pts the disease began with SLE signs, in 17% - with ARS signs and in 8% - with thrombocytopenia. 5 from 138 SLE pts without APS showed LA and APS clinical signs during follow- up. In 54% from 142 SAPS pts the disease began with an SLE sign, in 34% - with an APS sign and in 12% - with thrombocytopenia. At the onset of PAPS thrombocytopenia was much more seldom - in 5 from 84 pts. The rest had other APS signs at presentation. 8 pts showed PAPS transformation into SLE, Thrombotic complications frequency among SLE pts was 42%. They were significantly more frequent in APS (76% in PAPS and 90% in SAPS) than in SLE without APS (6%), x 2=I3I, p<0,000l. There was heart disease association with APS. Heart disease was present in 43% of PAPS pts, 27% of SLE+APS pts and only in 2% of SLE pts without APS. Neurological signs spectrum in PAPS and SLE+APS was similar but stroke in PAPS was significantly more frequent (46%) than in SAPS (26%). Digital necroses, nail bed infarctions and purpura, which probably develops with participation of inflammation, were not characteristic for PAPS. Conclusion. Our data shows difficulty of PAPS verification, possibility of its transformation into SAPS what proves necessity of clinical and laboratory monitoring for this pts category. Beside that despite of similarity of the two forms of APS some distinct features of PAPS and SAPS were revealed.

первичный и вторичный антифосфосипидный синдромprimary and secondary antiphospholipid syndromeReferences<div><p>Wilson W.A., Gharavi А.Е., Koike Т. et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthr. Rheum. 1999, 42. 1309-1311</p><p>Asherson R.A. A "primary" antiphospopholipid syndrome? J. Rheumatol., 1988. 15. 1742-1746</p><p>Asherson R.A. Khamashta M.A., Ordi-Ros J. et al. The "primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore), 1989, 68, 366374</p><p>Насонов Е.Л., Баранов А.А., Шилкина Н.П., Алекберова З.С. Патология сосудов при антифосфолнпидном синдроме (клиника, диагностика, лечение). М.-Ярославль, 1995, 161 стр.</p><p>Cervera R., Piette J.C., Font J. et al. Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthr. Rheum., 2002, 46, 1019-1027</p><p>Насонов Е.Л. Антифосфолипидный синдром. М., "Литтера”, 2004,379стр.</p><p>Font J., Lopez-Soto A. Cervera R. et al. The "primary" antiphospholipid syndrome: antiphospholipid antibody pat tern and clinical features of scries of 23 patients. Autoimmunity, 1991, 9, 69-75</p><p>Vianna I.L., Khamashta M.A., Ordi-Ros J. et al. Comparision of the primary and secondary antiphospholipid syndrome: a European multicenter study of 114 patients. AmJ.Med. 1994, 96, 3-9</p><p>Piette J.C. Wechsler B., Frances C. et al. Exclusion criteria for primary antiphospholipid syndrome. J.Rheumatol. 1993, 20, 1802-1804</p><p>Piette J.C., Wechsler B., Frances C., Godeau P. Systemic lupus erythematosus and antiphosphoplipid syndrome: reflection about the relevance of ARA criteria. J.Rheumatol., 1992, 19, 215-222</p><p>Hochberg M.C. Updating the American College of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthr. Rheum., 1997, 40, 1725</p><p>Tan E.M., Cohen A.S., Fries J.S. The 1982 revised criteria for the classification of svstemic lupus ervtheniatosus. Arth Rheum. 1982, 25, 1271-1277</p><p>Александрова E.H., Насонов Е.Л. Ковалев В.Ю. Количественный иммуноферментный метод определения антител к кардиолипину в сыворотке крови. Клин, реиматол. 1995, 4, 35-39</p><p>Bacharach J.M. Lie J.T. Homburger Н.А. The prevalence of vascular occlusive disease associated with antiphospholipid syndromes. Int.Angiol., 1992, II, 51-56 15,</p><p>Salafia C.M., Starzyk K., Lopez-Zeno J., Parke A. Fetal losses and other obstetric manifestations in the antiphospholipid syndrome. In 'The antiphospholipid syndrome” edited by Asherson R.A., Cervera R., Piette J,C., Shoenfeld Y. PRC Press Boca Raton New York London Tokyo, 1996, 117-131 16,</p><p>Garcia-ToiTes R., Amigo M-С., de la Rosa A. et al. Valvular heart disease in primary antiphospholipid syndrome (PAPS): clinical and morphological findings. Lupus, 1996, 5, 56-61</p><p>Nihoyannopoulos P., Gomez P.M., Joshi J. et al. Cardiac abnormalities in systemic lupus erythematosus. Association with raised anticardiolipin antibodies. Circulation, 1990, 82, 369-375</p><p>Asherson R.A., Hughes G.R.V. The expanding spectrum of Libman Sacks endocarditis: the role of antiphospholipid antibodies. Clin. Exp. Rheumatol., 1989, 7, 225-228</p><p>Brenner B. Blimenfeld Z., Markiewicz W., Reistier S.A. Cardiac involvement in patients with primary antiphospholipid syndrome.J.Am.Coll.Cardiol., 1991, 18, 931-936</p><p>Averback P. Primary cerebral venous thrombosis in yong adults: the diverse manifeststions of an unrecognized disease. Ann,Neurol., 1978, 3, 81-86</p><p>Levine S.R., Kieran S., Pusio K. et al. Cerebral venous sinus thrombosis with lupus anticoagulants: report: report of two cases. Stroke, 1987, 18, 801-803</p><p>Lau S.М., Bock G.H., Edson J.R., Michael A.T. Sagittal sinus thrombosis in nephrotic syndrome. J.Pediatr., 1980,97. 948-950</p><p>Brey R., Escalante A. Futrell N., Asherson R.A. Cerebral thrombosis and other neurological manifestation in the antiphospholipid syndrome. In "The antiphospholipid syndrome" edited by Asherson R.A., Cervera R. Piette J.C., Shoenfeld Y. PRC Press Boca Raton New York London - Tokyo. 1996, 3-13</p><p>Bouchez B. Arnott G., Hatron P. V. Choree et lupus ery- themateux dissemine avec anticoagulant circulnnt. Trois. Cas. Rev.Neurol. (Paris), 1985, 141, 571-577</p><p>Asherson R.A., Derksen E.H.W.N., Harris E.N. et al. Choreae in systemic lupus erthematosus and "lupus-like" disease. Association with antiphospholipid antibodies. Sem.Arthr. Rheum., 1987. 16. 253-259</p><p>Asherson R.A., Hughes G.R.V Antiphospholipid antibodies in chorea. J.Rheumatol., 1988, 15, 377-379</p><p>Brey R. Escalante A., Futrell N., Asherson R.A. Cerebral thrombosis and other neurological manifestation in the antiphospholipid syndrome. In "The antiphospholipid syndrome" edited by Asherson R.A., Cervera R., Piette J.C., Shoenfeld Y. PRC Press Boca Raton New York London - Tokyo. 1996, 3-13</p><p>Barber P.V., Arnold A.G., Evans G. Recurrent hormone dependent chorea: effects of prostogens. Clin.Endocrinol., 1976, 5, 291-293</p><p>Калашникова Л.А. Неврология антифосфолипидного синдрома. М. Медицина. 2003, 254</p><p>McHugh M.J,, Maymo J., Skinner R.P. et al. Anti- cardiolipin antibodies, livedo reticularis, and major cerebrovascular and renal disease in systemic lupus erythematosus. Ann.Rheum.Dts. 1988, 47, 110-115</p><p>Englert H.J., Loizou S., Derue G.G.M., Walport M.J., Hughes G.R.V. Clinical and immunollogic features of livedo reticularis in lupus: a case-control studv.Am.J.Med. 1989, 87, 408-410</p><p>Kalashnicova L.A., Nassonov E.L. Borisenko V.V., et al. Sneddon's syndromexariac pathology and antiphospholipid antibodies. Clin.Exp.Rheumatol., 1991, 9, 357-361</p><p>Alegre V.A., Gastineau D.A., Winkelmann R.K. Skin lesions associated with circulating lupus anticoagulant, Br.J.Dermatol., 1989, 120, 419-429</p><p>Becker J.C., Winkler B., Klingert S., Brocker E.B. Antiphospholipid syndrome associated with immunotherapy for patients with melanoma. Cancer, 1994, 73, 1621-1624</p><p>Stepansson E.A., Niemi K.M., Jouhikainen T. et al. Lupus anticoagulant and the skin. Along term follow-up study of SLE patients with special refernce of histopathological findings. Acta. Derm,Venerol.(Stokh.), 1991, 71, 416-422</p><p>Disdier P., Harle J.R., Andrac L. et al. Primary anetoderma with the antiphospholipid syndrome. J.Am.Acad.Dermatol., 1994, 30, 133-134</p></div><br /><div><p>Wilson W.A., Gharavi А.Е., Koike Т. et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthr. Rheum. 1999, 42. 1309-1311</p><p>Asherson R.A. A "primary" antiphospopholipid syndrome? J. Rheumatol., 1988. 15. 1742-1746</p><p>Asherson R.A. Khamashta M.A., Ordi-Ros J. et al. The "primary” antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore), 1989, 68, 366374</p><p>Насонов Е.Л., Баранов А.А., Шилкина Н.П., Алекберова З.С. Патология сосудов при антифосфолнпидном синдроме (клиника, диагностика, лечение). М.-Ярославль, 1995, 161 стр.</p><p>Cervera R., Piette J.C., Font J. et al. Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthr. Rheum., 2002, 46, 1019-1027</p><p>Насонов Е.Л. Антифосфолипидный синдром. М., "Литтера”, 2004,379стр.</p><p>Font J., Lopez-Soto A. Cervera R. et al. The "primary" antiphospholipid syndrome: antiphospholipid antibody pat tern and clinical features of scries of 23 patients. Autoimmunity, 1991, 9, 69-75</p><p>Vianna I.L., Khamashta M.A., Ordi-Ros J. et al. Comparision of the primary and secondary antiphospholipid syndrome: a European multicenter study of 114 patients. AmJ.Med. 1994, 96, 3-9</p><p>Piette J.C. Wechsler B., Frances C. et al. Exclusion criteria for primary antiphospholipid syndrome. J.Rheumatol. 1993, 20, 1802-1804</p><p>Piette J.C., Wechsler B., Frances C., Godeau P. Systemic lupus erythematosus and antiphosphoplipid syndrome: reflection about the relevance of ARA criteria. J.Rheumatol., 1992, 19, 215-222</p><p>Hochberg M.C. Updating the American College of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthr. Rheum., 1997, 40, 1725</p><p>Tan E.M., Cohen A.S., Fries J.S. The 1982 revised criteria for the classification of svstemic lupus ervtheniatosus. Arth Rheum. 1982, 25, 1271-1277</p><p>Александрова E.H., Насонов Е.Л. Ковалев В.Ю. Количественный иммуноферментный метод определения антител к кардиолипину в сыворотке крови. Клин, реиматол. 1995, 4, 35-39</p><p>Bacharach J.M. Lie J.T. Homburger Н.А. The prevalence of vascular occlusive disease associated with antiphospholipid syndromes. Int.Angiol., 1992, II, 51-56 15,</p><p>Salafia C.M., Starzyk K., Lopez-Zeno J., Parke A. Fetal losses and other obstetric manifestations in the antiphospholipid syndrome. In 'The antiphospholipid syndrome” edited by Asherson R.A., Cervera R., Piette J,C., Shoenfeld Y. PRC Press Boca Raton New York London Tokyo, 1996, 117-131 16,</p><p>Garcia-ToiTes R., Amigo M-С., de la Rosa A. et al. Valvular heart disease in primary antiphospholipid syndrome (PAPS): clinical and morphological findings. Lupus, 1996, 5, 56-61</p><p>Nihoyannopoulos P., Gomez P.M., Joshi J. et al. Cardiac abnormalities in systemic lupus erythematosus. Association with raised anticardiolipin antibodies. Circulation, 1990, 82, 369-375</p><p>Asherson R.A., Hughes G.R.V. The expanding spectrum of Libman Sacks endocarditis: the role of antiphospholipid antibodies. Clin. Exp. Rheumatol., 1989, 7, 225-228</p><p>Brenner B. Blimenfeld Z., Markiewicz W., Reistier S.A. Cardiac involvement in patients with primary antiphospholipid syndrome.J.Am.Coll.Cardiol., 1991, 18, 931-936</p><p>Averback P. Primary cerebral venous thrombosis in yong adults: the diverse manifeststions of an unrecognized disease. Ann,Neurol., 1978, 3, 81-86</p><p>Levine S.R., Kieran S., Pusio K. et al. Cerebral venous sinus thrombosis with lupus anticoagulants: report: report of two cases. Stroke, 1987, 18, 801-803</p><p>Lau S.М., Bock G.H., Edson J.R., Michael A.T. Sagittal sinus thrombosis in nephrotic syndrome. J.Pediatr., 1980,97. 948-950</p><p>Brey R., Escalante A. Futrell N., Asherson R.A. Cerebral thrombosis and other neurological manifestation in the antiphospholipid syndrome. In "The antiphospholipid syndrome" edited by Asherson R.A., Cervera R. Piette J.C., Shoenfeld Y. PRC Press Boca Raton New York London - Tokyo. 1996, 3-13</p><p>Bouchez B. Arnott G., Hatron P. V. Choree et lupus ery- themateux dissemine avec anticoagulant circulnnt. Trois. Cas. Rev.Neurol. (Paris), 1985, 141, 571-577</p><p>Asherson R.A., Derksen E.H.W.N., Harris E.N. et al. Choreae in systemic lupus erthematosus and "lupus-like" disease. Association with antiphospholipid antibodies. Sem.Arthr. Rheum., 1987. 16. 253-259</p><p>Asherson R.A., Hughes G.R.V Antiphospholipid antibodies in chorea. J.Rheumatol., 1988, 15, 377-379</p><p>Brey R. Escalante A., Futrell N., Asherson R.A. Cerebral thrombosis and other neurological manifestation in the antiphospholipid syndrome. In "The antiphospholipid syndrome" edited by Asherson R.A., Cervera R., Piette J.C., Shoenfeld Y. PRC Press Boca Raton New York London - Tokyo. 1996, 3-13</p><p>Barber P.V., Arnold A.G., Evans G. Recurrent hormone dependent chorea: effects of prostogens. Clin.Endocrinol., 1976, 5, 291-293</p><p>Калашникова Л.А. Неврология антифосфолипидного синдрома. М. Медицина. 2003, 254</p><p>McHugh M.J,, Maymo J., Skinner R.P. et al. Anti- cardiolipin antibodies, livedo reticularis, and major cerebrovascular and renal disease in systemic lupus erythematosus. Ann.Rheum.Dts. 1988, 47, 110-115</p><p>Englert H.J., Loizou S., Derue G.G.M., Walport M.J., Hughes G.R.V. Clinical and immunollogic features of livedo reticularis in lupus: a case-control studv.Am.J.Med. 1989, 87, 408-410</p><p>Kalashnicova L.A., Nassonov E.L. Borisenko V.V., et al. Sneddon's syndromexariac pathology and antiphospholipid antibodies. Clin.Exp.Rheumatol., 1991, 9, 357-361</p><p>Alegre V.A., Gastineau D.A., Winkelmann R.K. Skin lesions associated with circulating lupus anticoagulant, Br.J.Dermatol., 1989, 120, 419-429</p><p>Becker J.C., Winkler B., Klingert S., Brocker E.B. Antiphospholipid syndrome associated with immunotherapy for patients with melanoma. Cancer, 1994, 73, 1621-1624</p><p>Stepansson E.A., Niemi K.M., Jouhikainen T. et al. Lupus anticoagulant and the skin. Along term follow-up study of SLE patients with special refernce of histopathological findings. Acta. Derm,Venerol.(Stokh.), 1991, 71, 416-422</p><p>Disdier P., Harle J.R., Andrac L. et al. Primary anetoderma with the antiphospholipid syndrome. J.Am.Acad.Dermatol., 1994, 30, 133-134</p></div><br />

The authors declare that there are no conflicts of interest present.