Interdisziplinäre Betreuung von schwangeren Patientinnen mit Kollagenosen

Zusammenfassung

Kollagenosen sind neben der rheumatoiden Arthritis die häufigsten entzündlich-rheumatischen Erkrankungen. Da die Kollagenosen die Fertilität weit gehend unbeeinträchtigt lassen, stellt die Betreuung von schwangeren Patientinnen mit einer Kollagenose ein komplexes klinisches Problem dar, welches eine enge Kooperation der Gynäkologie, der Rheumatologie und der Pädiatrie erfordert. In diesem Artikel wird ein 4-Punkte-Programm vorgestellt, welches sich für die interdisziplinäre Betreuung von Patientinnen mit Kollagenosen in der Praxis bewährt hat, soweit als möglich auf evidenzbasierte Studien zurückgreift und sich den jeweiligen Gegebenheiten der behandelnden Praxen und Kliniken anpassen lässt. Das Programm umfasst das Erkennen von Risikopatientinnen, die präkonzeptionelle Diagnostik und Beratung, die Betreuung während der Schwangerschaft sowie die postpartale Risikominimierung. Klinische Schwerpunkte sind die immunsuppressive Therapie, die Antiphospholipid-Antikörper und der kongenitale Herzblock.

Abkürzungen

Ak:Antikörper

ANA:Antinukleäre Antikörper

APL:Antiphospholipid-Antikörper

APS:Antiphospholipid-Antikörpersyndrom

ASS:Acetylsalicylsäure

PSS:progressiv systemische Sklerodermie

SLE:systemischer Lupus erythematodes

SS:Schwangerschaft

Abstract

Connective tissue diseases affect frequently women during the childbearing period. As fertility is not considerably reduced in these patients, monitoring and treatment of a pregnant patient is a complex clinical setting that requires an intensive cooperation between gynecologists, rheumatologists and pediatricians. In this article, a 4-point-program for the clinical management of these patients is presented that addresses specifically the problems inherent with the identification of patients with connective tissue diseases, preconceptional diagnostics as well as monitoring and treatment during pregnancy and the postpartal period. Clinical aspects that are intensively discussed include immunosuppressive therapy during pregnancy, the management of antiphospholipid antibody-dependent problems and the prophylaxis and treatment options for congenital heart block.

Schlüsselwörter

Kollagenosen - systemischer Lupus erythematodes - Antiphospholipid-Antikörpersyndrom - kongenitaler Herzblock - Immunsuppressiva - Schwangerschaft

Key words

Connective tissue diseases - systemic lupus erythematosus - antiphospholipid antibodies syndrome - congenital heart block - immunosuppressants - pregnancy

Literatur

• 1 Cortes-Hernandez J, Ordi-Ros J, Paredes F, Casellas M, Castillo F, Vilardell-Tarres M. Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies.  Rheumatology. 2002;  41 643-50
• 2 Georgiou P E, Politi E N, Katsimbri P, Sakka V, Drosos A A. Outcome of lupus pregnancy: a controlled study.  Rheumatology. 2000;  39 1014-9
• 3 Heilmann L, von Tempelhoff G F, Kuse S. The influence of antiphospholipid antibodies on the pregnancy outcome of patients with recurrent spontaneous abortion.  Clin Appl Thromb Hemost. 2001;  7 281-5
• 4 Kiss E, Bhattoa H P, Bettembuk P, Balogh A, Szegedi G. Pregnancy in women with systemic lupus erythematosus.  Eur J Obstet Gynecol Reprod Biol. 2002;  101 129-34
• 5 Kutteh W H. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin in superior to low-dose aspirin alone.  Am J Obstet Gynecol. 1996;  174 1584-9
• 6 Rai R. Obstetric management of antiphospholipid syndrome.  J Autoimmun. 2000;  15 203-7
• 7 Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies).  Br Med J. 1997;  314 253-7
• 8 Cervera R, Font J, Carmona F, Balasch J. Pregnancy outcome in systemic lupus erythematosus: good news for the new millenium.  Autoimmun Rev. 2002;  1 354-9
• 9 Ichikawa K, Khamashta M A, Koike T, Matsuura E, Hughes G R. β2-Glykoprotein I reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome.  Arthritis Rheum. 1994;  37 1453-61
• 10 Kandiah D A, Sheng Y A, Krilis S A. β2-glykoprotein I: Target antigen for autoantibodies in the antiphospholipid syndrome.  Lupus. 1996;  5 381-5
• 11 Khamashta M. Lecture at the International Meeting on Autoimmunity and Pregnancy Loss, June 8, 2002, Park Hotel Villa Fiorita, Italy. www.rheuma21st.com, archived reports, publ. 01. Juli 2002. 
• 12 Asherson R A. Infections, Antiphospholipid antibodies, and antiphospholipid syndromes. www.rheuma21st.com, cutting edge reports, publ. 22. July 2002. 
• 13 Shehata H A, Nelson-Piercy C, Khamashta M A. Management of pregnancy in antiphospholipid syndrome.  Rheum Dis Clin N Am. 2001;  27 643-59
• 14 Tincani A, Branch W, Levy R A, Piette J C, Carp H, Rai R S, Khamashta M, Shoenfeld Y. Treatment of pregnant patients with antiphospholipid syndrome.  Lupus. 2003;  12 524-9
• 15 Alarcón-Segovia D, Boffa M C, Branch W, Cervera R, Gharavi A, Khamashta M, Shoenfeld Y, Wilson W, Roubey R. Prophylaxis of the antiphospholipid syndrome: a consensus report.  Lupus. 2003;  12 499-503
• 16 Dahlman T C. Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thrombophylaxis with heparin.  Am J Obstet Gynecol. 1993;  168 1265-70
• 17 De Swiet M, Ward P D, Fidler J, Horsman A, Katz D, Letsky E, Peacock M, Wise P H. Prolonged heparin therapy in pregnancy causes bone demineralization.  Br J Obstet Gynaecol. 1983;  90 1129-34
• 18 Smith R, Stevenson J C, Winearls C G, Woods C G, Wordsworth B P. Osteoporosis of pregnancy.  Lancet. 1985;  1 1178-80
• 19 Backos M, Rai R, Thomas E, Murphy M, Dore C, Regan L. Bone density changes in pregnant women treated with heparin: a prospective, longitudinal study.  Hum Reprod. 1999;  14 2876-80
• 20 Laskin C A, Bombardier C, Hannah M E, Mandel F P, Ritchie J W, Farewell V, Farine D, Spitzer K, Fielding L, Solonika C A, Yeung M. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss.  N Engl J Med. 1997;  337 148-53
• 21 Silver R K, MacGregor S N, Sholl J S, Hobart J M, Neerhof M G, Ragin A. Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients.  Am J Obstet Gynecol. 1993;  169 1411-7
• 22 Cimaz R, Spence D L, Hornberger L, Silverman E D. Incidence and spectrum of neonatal lupus: a prospective study of infants born to mothers with anti-Ro autoantibodies.  J Pediatrics. 2003;  142 678-83
• 23 Salomonsson S, Dörner T, Theander E, Bremme K, Larsson P, Wahren-Herlenius M. A serologic marker for fetal risk of congenital heart block.  Arthritis Rheum. 2002;  46 1233-41
• 24 Janssen N M, Genta M S. The effects of Immunosuppressive and anti-inflammatory medications on fertility, pregnancy and lactation.  Arch Int Med. 2000;  160 610-9
• 25 Regueiro M, Mardini H. Determination of thiopurine methyltransferase genotype or phenotype optimizes initial dosing of azathioprine for the treatment of Crohn’s disease.  J Clin Gastroenterol. 2002;  35 240-4
• 26 Colombel J F, Ferrari N, Debuysere H, Marteau P, Gendre J P, Bonaz B, Soule J C, Modigliani R, Touze Y, Catala P, Libersa C, Broly F. Genotype analysis of thiopurine S-methyltransferase in patients with Crohn’s disease and severe meylosuppression during azathioprine therapy.  Gastroenterology. 2000;  118 1025-30
• 27 Pujals J M, Figueras G, Puig J M. Osseus malformation in baby born to woman on cyclosporin.  Lancet. 1989;  1 667
• 28 Ostensen M. Treatment with immunosuppressive and disease-modifying drugs during pregnancy and lactation.  Am J Reprod Immunol. 1992;  28 148-52
• 29 Hussein M M, Mooji J MV, Roujouleh H. Cyclosporine in the treatment of lupus nephritis including two patients treated during pregnancy.  Clin Nephrol. 1993;  40 160-3
• 30 Leflunomid (Beipackzettel). Hoechst Marion Roussel 1998
• 31 Petri M. Immunosuppressive drug use in pregnancy.  Autoimmunity. 2003;  36 51-6
• 32 Chakravarty E F, Sanchez-Yamamoto D, Bush T M. The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: a survey of practic patterns and pregnancy outcomes.  J Rheumatol. 2003;  30 241-6
• 33 Abu-Shakra M, Shoenfeld Y. Azathioprine therapy for patients with systemic lupus erythematosus.  Lupus. 2001;  10 152-3
• 34 Ostensen M, Villiger P M. Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus.  Lupus. 2001;  10 135-9
• 35 Cervera R. Lecture at the International Meeting on Autoimmunity and Pregnancy Loss, June 8, 2002, Park Hotel Villa Fiorita, Italy. www.rheuma21st.com, archived reports, publ. 01. July 2002. 
• 36 Müller-Ladner U, Benning K, Röther E, Lang B. Neonatal lupus erythematosus as an example of passively acquired autoimmunity.  Immun Infekt. 1992;  20 117-21
• 37 Askanase A, Friedman D, Glickstein J, Kim M, Buyon J. Potential therapeutic window from normal heart rate (NHR) to advanced heart block and early detection of first degree block by echocardiographic measurement of the mechanical PR Interval.  Arthritis Rheumatism. 2002;  46 (Suppl.) S321
• 38 Brucato A, Doria A, Frassi M, Castellino G, Franceschini F, Farden D, Pisoni M P, Solerte L, Muscara M, Lojacono A, Motta M, Cavazzana I, Ghiradello A, Vescovi F, Tombini V, Cimaz R, Gambari P F, Meroni P L, Canesi B, Tincani A. Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro/SSA antibodies: a prospective controlled study.  Lupus. 2002;  11 716-21
• 39 Allan L D. Research protocol for fetuses with complete heart block.  Ultrasound Obstet Gynecol. 1995;  5 349-52
• 40 Costedoat-Chalumenau N, Amoura Z, Le Thi Hong D, Wechsler B, Vauthier D, Ghillani P, Papo T, Fain O, Musset L, Piette J -C. Questions about dexamethasone use for the prevention of anti-SSA related congenital heart block.  Ann Rheum Dis. 2003;  62 1010-2
• 41 Buyon J P, Clancy R M. Neonatal Lupus: Review of proposed pathogenesis and clinical data from the US-based research registry for neonatal lupus.  Autoimmunity. 2003;  36 41-50
• 42 Kaaja R, Julkunen H, Ammala P, Teppo A M, Kurki P. Congenital heart block: successful prophylactic treatment with intravenous gamma globulin and corticosteroid therapy.  Am J Obstet Gynecol. 1991;  165 1333-4
• 43 Yoshida H, Iwamoto M, Sakakibara H, Shigeta H, Hirahara F, Sato K. Treatment of fetal congenital complete heart block with maternal administration of beta-sympathomimetics (terbutaline): a case report.  Gynecol Obstet Invest. 2001;  52 142-4
• 44 Stika C S, Gross G A, Leguizamon G, Gerber S, Levy R, Mathur A, Bernhard L M, Nelson D M, Sadovsky Y. A prospective randomized safety trial of celecoxib for treatment of preterm labor.  Am J Obstet Gynekol. 2002;  187 653-60
• 45 Valentini G, Black C M. Pregnancy in systemic sclerosis.  Best Pract Res Clin Rheumatol. 2002;  16 807-16