Das Antiphospholipid-Syndrom im Kindes- und Jugendalter

Zusammenfassung

Wenngleich das Antiphospholipid-Syndrom (APS) im Kindes- und Jugendalter eine seltene Erkrankung ist, sollte es frühzeitig erkannt und therapiert werden, da ansonsten eine hohe Morbidität und Mortalität zu befürchten sind. Übergänge von der primären in die sekundäre Form mit assoziierter Grunderkrankung treten dreimal häufiger auf als im Erwachsenenalter. Die Therapie ist komplex und orientiert sich an den Empfehlungen für erwachsene APS-Patienten. Allerdings sollten pädiatriespezifische Besonderheiten beachtet werden.

Summary

Albeit antiphophospholipid syndrome is rare in childhood early diagnosis is crucial to prevent high rates of morbidity and mortality. Transition from primary to secondary manifestation with associated diseases are three times more common compared to adulthood. Treatment is complex and based on recommendations for adults, though special features in pediatric patients should be kept in mind.

Schlüsselwörter

Antiphospholipid-Syndrom - APS - Cardiolipin-Antikörper - Lupusantikoagulans - β2-Glyko-protein-Antikörper

Keywords

Antiphospholipid syndrome - APS - cardiolipin antibodies - lupus anticoagulans - β2-glyco-protein antibodies

• Literatur

• 1 Amin NM. Antiphospholipid syndromes in infectious diseases. Hematol Oncol Clin North Am 2008; 22 1 131-143 vii-viii.
• 2 Andreoli L, Chighizola CB. et al. Clinical Characterization of Antiphospholipid Syndrome by Detection of IgG Antibodies Against beta2-Glycoprotein I Domain 1 and Domain 4/5: Ratio of Anti-Domain 1 to Anti-Domain 4/5 As a Useful New Biomarker for Antiphospholipid Syndrome. Arthritis Rheumatol 2015; 67 (08) 2196-2204.
• 3 Avcin T, Cimaz R. et al. The Ped-APS Registry: the antiphospholipid syndrome in childhood. Lupus 2009; 18 (10) 894-899.
• 4 Avcin T, Cimaz R. et al. Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics 2008; 122 (05) e1100-e1107.
• 5 Avcin T, O’Neill K. Antiphospholipid Syndrome. In: Petty et al. Textbook of Pediatric Rheumatology. Oxford: Elsevier Ltd; 2016
• 6 Avcin T, Silverman ED. Antiphospholipid antibodies in pediatric systemic lupus erythematosus and the antiphospholipid syndrome. Lupus 2007; 16 (08) 627-633.
• 7 Berkun Y, Padeh S. et al. Antiphospholipid syndrome and recurrent thrombosis in children. Arthritis Rheum 2006; 55 (06) 850-855.
• 8 Berman H, Rodriguez-Pinto I. et al. Pediatric catastrophic antiphospholipid syndrome: descriptive analysis of 45 patients from the „CAPS Registry. Autoimmun Rev 2014; 13 (02) 157-162.
• 9 Berube C, Mitchell L. et al. The relationship of antiphospholipid antibodies to thromboembolic events in pediatric patients with systemic lupus erythematosus: a cross-sectional study. Pediatr Res 1998; 44 (03) 351-356.
• 10 Bhakhri BK, Katewa S. et al. Primary antiphos -pholipid antibody syndrome presenting with adrenal insufficiency in a child: case report and review of literature. Lupus 2011; 20 (11) 1203-1208.
• 11 Binstadt BA, Caldas AM. et al. (2003). Rituximab therapy for multisystem autoimmune diseases in pediatric patients. J Pediatr 2003; 143 (05) 598-604.
• 12 Bucciarelli S, Erkan D. et al. Catastrophic antiphospholipid syndrome: treatment, prognosis, and the risk of relapse. Clin Rev Allergy Immunol 2009; 36 2–3 80-84.
• 13 Bucciarelli S, Espinosa G. et al. The CAPS Registry: morbidity and mortality of the catastrophic antiphospholipid syndrome. Lupus 2009; 18 (10) 905-912.
• 14 Cervera R. C.R.P. Group Catastrophic antiphos-pholipid syndrome (CAPS): update from the ‘CAPS Registry’. Lupus. 2010; 19 (04) 412-418.
• 15 Cervera R, Piette JC. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002; 46 (04) 1019-1027.
• 16 Cervera R, Rodriguez-Pinto I. et al. 14^th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome. Autoimmun Rev 2014; 13 (07) 699-707.
• 17 Cervera R, Serrano R. et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis 2015; 74 (06) 1011-1018.
• 18 Cohen D, Berger SP. et al. Diagnosis and management fo the antiphospholipid syndrome. BMJ 2010; 14: 340.
• 19 Crowther MA, Ginsberg JS. et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphos -pholipid antibody syndrome. N Engl J Med 2003; 349 (12) 1133-1138.
• 20 Dörner T. Akt Rheum (zum Druck angenommen)..
• 21 Erkan D, Espinosa G. et al. Catastrophic antiphos -pholipid syndrome: updated diagnostic algorithms. Autoimmun Rev 2010; 10 (02) 74-79.
• 22 Erkan D, Yazici Y. et al. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford) 2002; 41 (08) 924-929.
• 23 Finazzi G, Marchioli R. et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphos -pholipid syndrome (WAPS). J Thromb Haemost 2005; 03 (05) 848-853.
• 24 Frances C, Niang S. et al. Dermatologic manifestations of the antiphospholipid syndrome: two hundred consecutive cases. Arthritis Rheum 2005; 52 (06) 1785-1793.
• 25 Gattorno M, Falcini F. et al. Outcome of primary antiphospholipid syndrome in childhood. Lupus 2003; 12 (06) 449-453.
• 26 Giordano P, Tesse R. et al. Clinical and laboratory characteristics of children positive for antiphos -pholipid antibodies. Blood Transfus 2012; 10 (03) 296-301.
• 27 Gris JC, Bouvier S. et al. Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood 2012; 119 (11) 2624-2632.
• 28 Hancock HS, Wang M. et al. Cardiac findings and long-term thromboembolic outcomes following pulmonary embolism in children: a combined retrospective-prospective inception cohort study. Cardiol Young 2013; 23 (03) 344-352.
• 29 Huang HJ, Wang JN. et al. Intrapulmonary thrombolytic therapy in a child with acute pulmonary embolism due to primary antiphospholipid syndrome. Acta Paediatr Taiwan 2002; 43 (06) 351-353.
• 30 Kenet G, Aronis S. et al. Impact of persistent antiphospholipid antibodies on risk of incident symptomatic thromboembolism in children: a systematic review and meta-analysis. Semin Thromb Hemost 2011; 37 (07) 802-809.
• 31 Levine SR, Brey RL. et al. Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 2004; 291 (05) 576-584.
• 32 Levine SR, Salowich-Palm L. et al. IgG anticardiolipin antibody titer > 40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study. Stroke 1997; 28 (09) 1660-1665.
• 33 Levy DM, Massicotte MP. et al. Thromboembolism in paediatric lupus patients. Lupus 2003; 12 (10) 741-746.
• 34 Male C, Lechner K. et al. Clinical significance of lupus anticoagulants in children. J Pediatr 1999; 134 (02) 199-205.
• 35 Manco-Johnson MJ. How I treat venous thrombosis in children. Blood 2006; 107 (01) 21-29.
• 36 Manco-Johnson MJ, Nuss R. Lupus anticoagulant in children with thrombosis. Am J Hematol 1995; 48 (04) 240-243.
• 37 Martinez-Zamora MA, Peralta S. et al. Risk of thromboembolic events after recurrent spontaneous abortion in antiphospholipid syndrome: a case-control study. Ann Rheum Dis 2012; 71 (01) 61-66.
• 38 Miyakis S, Lockshin MD. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 04 (02) 295-306.
• 39 Nuss R, Hays T. et al. Antiphospholipid antibodies and coagulation regulatory protein abnormalities in children with pulmonary emboli. J Pediatr Hematol Oncol 1997; 19 (03) 202-207.
• 40 Ohtomo Y, Nagaoka R. et al. Non-lupus nephropathy associated with antiphospholipid antibodies. Pediatr Nephrol 2000; 15 1–2 136-138.
• 41 Okuma H, Kitagawa Y. et al. Comparison between single antiplatelet therapy and combination of antiplatelet and anticoagulation therapy for secondary prevention in ischemic stroke patients with antiphospholipid syndrome. Int J Med Sci 2009; 07 (01) 15-18.
• 42 Pierangeli SS, Erkan D. Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet?. Lupus 2010; 19 (04) 475-485.
• 43 Polido-Pereira J, Ferreira D. et al. Rituximab use in pediatric autoimmune diseases: four case reports. Ann N Y Acad Sci 2009; 1173: 712-720.
• 44 Roggenbuck D, Egerer K. et al. Antiphospholipid antibody profiling: time for a new technical approach?. Autoimmun Rev 2012; 11 (11) 821-826.
• 45 Roggenbuck D, Somma V. et al. Autoantibody profiling in APS. Lupus 2014; 23 (12) 1262-1264.
• 46 Ruffatti A, Del Ross T. et al. Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study. Ann Rheum Dis 2011; 70 (06) 1083-1086.
• 47 Ruiz-Irastorza G, Crowther M. et al. Antiphos -pholipid syndrome. Lancet 2010; 376 9751 1498-1509.
• 48 Ruiz-Irastorza G, Cuadrado MJ. et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus 2011; 20 (02) 206-218.
• 49 Ruiz-Irastorza G, Hunt BJ. et al. A systematic review of secondary thromboprophylaxis in patients with antiphospholipid antibodies. Arthritis Rheum 2007; 57 (08) 1487-1495.
• 50 Specker C. [Antiphospholipid syndrome]. Z Rheumatol 2015; 74 (03) 191-198.
• 51 Tarr T, Lakos G. et al. Primary antiphospholipid syndrome as the forerunner of systemic lupus erythematosus. Lupus 2007; 16 (05) 324-328.
• 52 Tavil B, Ozyurek E. et al. Antiphospholipid antibodies in Turkish children with thrombosis. Blood Coagul Fibrinolysis 2007; 18 (04) 347-352.
• 53 Tektonidou MG, Laskari K. et al. Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies. Arthritis Rheum 2009; 61 (01) 29-36.
• 54 Uthman IW, Khamashta MA. Livedo racemosa: a striking dermatological sign for the antiphospholipid syndrome. J Rheumatol 2006; 33 (12) 2379-2382.
• 55 Wells PS, Anderson DR. et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349 (13) 1227-1235.
• 56 Zamora-Ustaran A, Escarcega-Alarcon RO. et al. Antiphospholipid syndrome in Mexican children. Isr Med Assoc J 2012; 14 (05) 286-289.