Zusammenfassung
Der neonatale Lupus erythematodes (NLE) umfasst vorrangig den kutanen NLE und den angeborenen AV-Block und wird durch eine antikörpervermittelte Entzündungsreaktion ausgelöst, wobei transplazentar übertragenen mütterlichen Autoantikörpern gegen den RNA-Proteinkomplex Ro(SS-A)/La(SS-B) eine pathogenetische Bedeutung zukommt. Die Krankheitsmanifestationen des NLE sind mit Ausnahme des kompletten kongenitalen Herzblockes (CCHB) durch den Abbau der mütterlichen Antikörper in der Zirkulation des Neugeborenen limitiert. Dabei gilt der CCHB als eine vital bedrohliche Komplikation, die insbesondere bei Müttern mit subklinischem Sjögren-Syndrom und koinzidenten Autoantikörpern gegen Ro(SS-A) und La(SS-B) auftreten kann. Die Arbeit gibt einen aktuellen Überblick zu diagnostischen und differenzialtherapeutischen Aspekten des angeborenen atrioventrikulären (AV-)Blockes, der enger mit einem mütterlichen Sjögren-Syndrom als mit einem systemischen Lupus erythematodes (SLE) assoziiert ist.
Abstract
Neonatal lupus erythematosus (NLE) comprises predominantly cutaneous neonatal lupus erythematosus and congenital atrioventricular block and is triggered by an inflammatory reaction mediated by antibodies. In this regard, pathogenetic significance is ascribed to transplacentally transfered maternal auto-antibodies against the RNA protein complex Ro(SS-A) / La(SS-B). The manifestations of NLE are limited due to degradation of the maternal antibodies, except, however, the manifestations of complete congenital heart block (CCHB). It must be beared in mind that CCHB is rated a life-threatening complication that can occur especially in mothers suffering from sub-clinical Sjögren’s syndrome co-incidentally with auto-antibodies against Ro(SS-A) and La(SS-B). The following article is an update review of the diagnostic and differential therapeutic aspects of neonatal atrioventricular block that is more closely associated with a maternal Sjögren’s syndrome than with systemic lupus erythematosus.
Literatur
-
1
Buyon J P.
Neonatal lupus syndromes.
Curr Opin Rheumatol.
1994;
6
523-529
-
2
Silverman E D, Laxer R M.
Neonatal lupus erythematosus.
Rheum Dis Clin North Am.
1997;
23
599-618
-
3
Eronen M, Siren M K, Ekblad H. et al .
Short- and long-term outcome of children with congenital complete heart block diagnosed in utero or as a newborn.
Pediatrics.
2000;
106
86-91
-
4
Buyon J P, Hiebert R, Copel J. et al .
Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry.
J Am Coll Cardiol.
1998;
31
1658-1666
-
5
Silverman E D, Lang B.
An overview of the treatment of childhood SLE.
Scand J Rheumatol.
1997;
26
241-246
-
6
Franco H L, Weston W L, Peebles C. et al .
Autoantibodies directed against sicca syndrome antigens in the neonatal lupus syndrome.
J Am Acad Dermatol.
1981;
4
67-72
-
7
Kephart D C, Hood A F, Provost T T.
Neonatal lupus erythematosus: new serologic findings.
J Invest Dermatol.
1981;
77
331-333
-
8
Deng J S, Bair L W, Shen-Schwarz S. et al .
Localisation of Ro(SS-A) antigen in the cardiac conduction system.
Arthritis Rheum.
1987;
11
1232-1238
-
9
Ishibashi-Ueda H, Yutani C, Imakita M. et al .
An autopsy case of congenital complete heart block in a newly born of a mother with systemic lupus erythematosus.
Pediatr Cardiol.
1988;
9
157-161
-
10
Stiehm E R.
Fetal defense mechanisms.
Am J Dis Child.
1975;
129
438-442
-
11
Scott J S, Maddison P J, Taylor P V. et al .
Connective tissue disease, antibodies to ribonucleoprotein and congenital heart block.
N Engl J Med.
1983;
309
209-212
-
12
Reed D R, Lee L A, Harmon C.
Autoantibodies to SS-A/Ro in infants with congenital heart block.
J Pediatr.
1983;
103
889-891
-
13
Silverman E D, Mamula M, Hardin J A. et al .
Importance of the immune response to the Ro/La particle in the development of congenital heart block and neonatal lupus erythematosus.
J Rheumatol.
1991;
18
120-124
-
14
Buyon J P, Ben-Chetrit E, Karp S. et al .
Acquired congenital heart block. Pattern of maternal antibody response to biochemically defined antigens of the SSA/Ro-SSB/La system in neonatal lupus.
J Clin Invest.
1989;
84
627-634
-
15
Dörner T, Hiepe F, Göldner B. et al .
Investigations into Ro-specific antibody-associated congenital cardiac conduction defects.
Clin Invest.
1992;
70
492-496
-
16
Buyon J P, Waltuck J, Caldwell K. et al .
Relationship between maternal and neonatal levels of antibodies to 48 kD SSB(La), 52 kD SSA(Ro), and 60 kD SSA(Ro) in pregnancies complicated by congenital heart block.
J Rheumatol.
1994;
21
1943-1950
-
17
Taylor P V, Taylor K F, Norman A. et al .
Prevalence of maternal Ro(SS-A) and La(SS-B) autoantibodies in relation to congenital heart block.
Br J Rheumatol.
1988;
27
128-132
-
18
Dörner T, Chaoui R, Feist E. et al .
Significantly increased maternal and fetal IgG autoantibody levels to 52 kD Ro(SS-A) and La(SS-B) in complete congenital heart block.
J Autoimm.
1995;
8
675-684
-
19
Carreira P E, Gutierrez L arraya F, Gomez R eino JJ.
Successful intrauterine therapy with dexamethasone for fetal myocarditis and heart block in a woman with systemic lupus erythematosus.
J Rheumatol.
1993;
20
1204-1207
-
20
Deng J S, Sontheimer R D, Gilliams J N.
Expression of Ro/SS-A antigen in human skin and heart.
J Invest Dermatol.
1985;
85
412-416
-
21
Julkunen H, Kurki P, Kaaja R. et al .
Isolated congenital heart block: long-term outcome of mothers and characterization of the immune response to SS-A/Ro and SS-B/La.
Arthritis Rheum.
1993;
36
1588-1598
-
22
Ramsey-Goldman R, Hom D, Deng J S. et al .
Anti-SS-A antibodies and fetal outcome in maternal systemic lupus erythematosus.
Arthritis Rheum.
1986;
10
1269-1273
-
23
Derksen R H, Meilof J F.
Anti-Ro/SS-A and anti-La/SS-B autoantibody levels in relation to systemic lupus erythematosus disease activity and congenital heart block. A longitudinal study comprising two consecutive pregnancies in a patient with systemic lupus erythematosus.
Arthritis Rheum.
1992;
35
953-959
-
24
Meilof J F, Frohn-Mulder I M, Stewart P A. et al .
Maternal autoantibodies and congenital heart block: no evidence for the existence of a unique heart block-associated anti-Ro/SS-A autoantibody profile.
Lupus.
1993;
2
239-246
-
25
Miranda-Carus M E, Askanase A D, Clancy R M. et al .
Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages.
J Immunol.
2000;
165
5345-5351
-
26
Buyon J P, Tseng C E, Di Donato F. et al .
Cardiac expression of 52beta, an alternative transcript of the congenital heart block-associated 52-kd SS-A/Ro autoantigen, is maximal during fetal development.
Arthritis Rheum.
1997;
40
655-660
-
27
Miranda-Carus M E, Boutjdir M, Tseng C E. et al .
Induction of antibodies reactive with SSA/Ro-SSB/La and development of congenital heart block in a murine model.
J Immunol.
1998;
161
5886-5892
-
28
Alexander E L, Buyon J P, Lane J. et al .
Anti-SS-A/Ro SS-B/La antibodies bind to neonatal rabbit cardiac cells and preferentially inhibit in vitro cardiac repolarization.
J Autoimmun.
1989;
2
463-469
-
29
Garcia S, Nascimento H M, Bonfa E. et al .
Cellular mechanisms of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts.
J Clin Invest.
1994;
93
718-724
-
30
Julkunen H, Kaaja R, Siren M K. et al .
Immune-mediated congenital heart block (CHB): identifying and counseling patients at risk for having children with CHB.
Semin Arthritis Rheum.
1998;
28
97-106
-
31
McCune A B, Weston W L, Lee L A.
Maternal and fetal outcome in neonatal lupus erythematosus.
Ann Int Med.
1987;
106
518-523
-
32
Reichlin M, Friday K, Harley J B.
Complete congenital heart block followed by anti-Ro/SS-A in adult life. Studies of an informative family.
Am J Med.
1988;
2
339-344
-
33
Waltuck J, Buyon J P.
Autoantibody-associated congenital heart block: outcome in mothers and children.
Ann Intern Med.
1994;
120
544-551
-
34
Dorner T, Feist E, Chaoui R. et al .
Enhanced frequency of autoimmune congenital heart block in female offspring.
Rheumatology.
1999;
38
380-382
-
35
Silverman E D.
Congenital heart block and neonatal lupus erythematosus: prevention is the goal.
J Rheumatol.
1993;
20
1101-1104
-
36
Julkunen H, Siren M K, Kaaja R. et al .
Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La -comparison with systemic lupus erythematosus and primary Sjögren’s syndrome.
Br J Rheumatol.
1995;
34
901-907
-
37
Bierman F Z, Baxi L, Jaffe I. et al .
Fetal hydrops and congenital complete heart block: response to maternal steroid therapy.
J Pediatr.
1988;
112
646-648
-
38
Watson W J, Katz V L.
Steroid therapy for hydrops associated with antibody-mediated congenital heart block.
Am J Obstet Gynecol.
1991;
165
553-554
-
39
Herreman G, Sauvaget F, Genereau T. et al .
Congenital atrioventricular block and maternal autoimmune diseases.
Ann Med Interne Paris.
1990;
141
234-238
-
40
Olah K S, Gee H.
Antibody mediated complete congenital heart block in the fetus.
Pacing Clin Electrophysiol.
1993;
16
1872-1879
-
41
Zemlin M, Bauer K, Dorner T. et al .
Intrauterine therapy and outcome in four pregnancies of one mother with anti ro-autoantibody positive Sjoegren’s syndrome.
Z Geburtshilfe Neonatol.
2002;
206
22-25
-
42
Buyon J P, Swersky S H, Fox H E. et al .
Intrauterine therapy for presumptive fetal myocarditis with acquired heart block due to systemic lupus erythematosus. Experience in a mother with a predominance of SS-B (La) antibodies.
Arthritis Rheum.
1987;
30
44-49
-
43
Feist E, Dörner T, Wagenmann A. et al .
Erfolgreiches therapeutisches Management einer Risikoschwangerschaft bei primärem Sjögren-Syndrom mit Plasmapherese und Dexamethason.
Z Rheumatol.
1996;
55
127-132
-
44
Kaaja R, Julkunen H, Ämmälä P. et al .
Congenital heart block: Successful prophylactic treatment with intravenous gamma globulin and corticosteroid therapy.
Am J Obstet Gynecol.
1991;
165
1333-1334
-
45
Tseng C E, Buyon J P.
Neonatal lupus syndromes.
Rheum Dis Clin North Am.
1997;
23
31-54
-
46
Rider L G, Buyon J P, Rutledge J. et al .
Treatment of neonatal lupus: case report and review of the literature.
J Rheumatol.
1993;
20
1208-1211
-
47
Hansky B, Breymann T, Welisch E. et al .
Herzschrittmachertherapie im Kindesalter.
Deutsches Ärzteblatt.
1999;
42
2150-2155
PD Dr. med. Thomas Dörner
Klinik für Rheumatologie und Klinische Immunologie, Charité, Humboldt Universität
Schumannstraße 20/21
10117 Berlin
Email: thomas.doerner@charite.de
