The health of mothers of children with cutaneous neonatal lupus erythematosus differs from that of mothers of children with congenital heart block

doi:10.1016/S0002-9343(00)00408-3

The American Journal of Medicine

Volume 108, Issue 9, 15 June 2000, Pages 705-709

https://doi.org/10.1016/S0002-9343(00)00408-3 Get rights and content

Abstract

PURPOSE: Neonatal lupus erythematosus is caused by the transplacental passage of maternal autoantibodies. The aim of this study was to determine the risk of connective tissue disorders in mothers of children with cutaneous neonatal lupus erythematosus, as compared with the risk in mothers of children with congenital heart block, which is also often caused by maternal autoantibodies.

SUBJECTS AND METHODS: We prospectively studied all mothers of children with cutaneous neonatal lupus erythematosus during a 14-year period at the Hospital for Sick Children, Toronto, Ontario, Canada. We identified 28 mothers, of whom 24 were eligible for study. The health and antibody status of the mothers were determined at the birth of the child and at follow-up.

RESULTS: All mothers had anti-Ro antibodies at the time of birth. Initially 10 mothers were healthy and 14 mothers had either a defined (n = 9) or an undifferentiated (n = 5) autoimmune disorder. At a mean follow-up of 7 years, 13 (1 of whom had died) had a defined connective tissue disease, and 5 had an undifferentiated autoimmune disorder. Only 6 (25%) remained asymptomatic. By comparison, 36 (56%) of 64 mothers of children with congenital heart block were asymptomatic at follow-up (P <0.005).

CONCLUSIONS: The majority of mothers of children with cutaneous neonatal lupus erythematosus had a defined or undifferentiated autoimmune disorder at the time of the child’s birth, and others developed these conditions during follow-up. The health of these mothers appears to differ from that of mothers of children with congenital heart block.

Section snippets

Patients

All mothers of infants with a diagnosis of cutaneous neonatal lupus erythematosus seen at the Hospital for Sick Children, Toronto, Ontario, Canada, between January 1982 and January 1996 were eligible for the study. The diagnosis of cutaneous neonatal lupus erythematosus was based on clinical assessment by a staff rheumatologist or dermatologist. Referrals were made from family practitioners, pediatricians, dermatologists, and obstetricians in the community. Some patients were identified as part

Results

The mean (± SD) age of the mothers at delivery of the infant with cutaneous neonatal lupus erythematosus was 28 ± 3 years (range 18 to 38). Ten mothers were white, 3 were black, 5 were South Asian, and 6 were Southeast Asian.

At the time of delivery of the child with cutaneous neonatal lupus erythematosus, 10 (42%) of the mothers were well without any signs or symptoms of a connective tissue disease, 9 (37%) had been previously diagnosed with a defined connective tissue disease, and 5 (21%) had

Discussion

Neonatal lupus erythematosus is associated with the transplacental passage of maternal autoantibodies, particularly anti-Ro and anti-La antibodies. Although circulating autoantibodies are usually associated with disease, the majority of mothers of children with congenital heart block are clinically well, despite the presence of these antibodies 17, 18, 20, 21, 22. By contrast, we observed that the mothers of children with cutaneous neonatal lupus erythematosus frequently had systemic lupus

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In 1%–18% of pregnancies, fetal exposure to maternal anti-SSA/Ro and anti-SSB/La autoantibodies transported across the placenta via FcγRn can result in a spectrum of injury referred to as neonatal lupus. Disease in the offspring may be independent of the maternal health status as often the mother has no previous history of any autoimmune or rheumatic disorder. The classic manifestations include cardiac injury in utero and a cutaneous rash in the neonatal period though other organ systems may be affected as well. The antibodies associating with injury are reactive with an intracellular target, providing a rare opportunity to evaluate pathways leading to autoimmune-mediated tissue injury and to translate these findings to management. This chapter extensively covers the epidemiology, clinical spectrum, proposed pathogenesis, biomarkers, and guidelines for prevention and therapy, taking into account new advances from the bench and bedside, including the introduction of home monitoring.
Neonatal lupus syndrome: Literature review
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Le lupus érythémateux néonatal se manifeste par une atteinte cutanée, hématologique, hépatique ou cardiaque incluant un éventuel bloc auriculo-ventriculaire congénital (BAVc) survenant sur un cœur indemne de cardiopathie malformative, une cardiomyopathie dilatée et une fibroélastose endocardique. Ce syndrome rare est constamment associé à la présence chez la mère d’anticorps anti-SSA/Ro et/ou anti-SSB/La. La fréquence du BAVc chez les femmes ayant une connectivite associée à un anticorps anti-SSA/Ro est estimée entre 1 et 2 %, et le risque de récurrence est évalué à environ 19 % lors d’une grossesse ultérieure. Les atteintes cutanées et systémiques sont transitoires, contrairement aux atteintes cardiaques et notamment au BAVc qui est définitif, associé à une morbidité et à une mortalité d’environ 18 %. La mise en place d’un pacemaker est nécessaire dans 2/3 des cas. Une myocardite peut être associée d’emblée ou apparaître plus tardivement. Les mères d’enfants ayant un BAVc sont le plus souvent asymptomatiques au moment de la découverte du BAVc. La physiopathologie n’est pas complètement élucidée à ce jour. Lorsqu’une femme enceinte est porteuse d’un anticorps anti-SSA/Ro, une surveillance échographique obstétricale sera réalisée tous les 15 jours entre 16 et 24 semaines d’aménorrhée et un électrocardiogramme sera fait de principe chez l’enfant. L’intérêt d’un traitement curatif in utero du BAVc par corticoïdes fluorés n’est à ce jour pas démontré. Un traitement préventif par hydroxychloroquine semble diminuer le risque de récidive du BAVc chez les femmes ayant déjà eu un enfant atteint. Une étude prospective est en cours pour confirmer ces résultats.
Neonatal lupus syndrome is associated with transplacental passage of maternal anti-SSA/Ro and anti-SSB/La antibodies. Children display cutaneous, hematological, liver or cardiac features. Cardiac manifestations include congenital heart block (CHB); endocardial fibroelastosis and dilated cardiomyopathy. The prevalence of CHB in newborns of anti-Ro/SSA positive women with known connective tissue disease is between 1 and 2% and the risk of recurrence is around 19%. Skin and systemic lesions are transient, whereas CHB is definitive and associated with significant morbidity and a mortality of 18%. A pacemaker must be implanted in 2/3 of cases. Myocarditis may be associated or appear secondly. Mothers of children with CHB are usually asymptomatic or display Sjogren's syndrome or undifferentiated connective tissue disease. In anti-Ro/SSA positive pregnant women, fetal echocardiography should be performed at least every 2 weeks from the 16th to 24th week gestation. An electrocardiogram should be performed for all newborn babies. The benefit of fluorinated corticosteroid therapy for CHB detected in utero remains unclear. Maternal use of hydroxychloroquine may be associated with a decreased recurrent CHB risk in a subsequent offspring. A prospective study is actually ongoing to confirm these findings.
Neonatal Lupus Erythematosus
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Neonatal lupus erythematosus
2011, Textbook of Pediatric Rheumatology
Neonatal Lupus
2011, Systemic Lupus Erythematosus
Neonatal lupus (NL) is the occurrence of systemic lupus erythematosus (SLE) symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus, and sometimes with systemic abnormalities such as heart block or hepatosplenomegaly. This chapter reviews the current understanding of NL. Fetal exposure to maternal antibodies reactive with several components of the SSA/Ro-SSB/La ribonucleoprotein complex is a requisite factor for the development of NL. Although NL is uncommon, its discussion is an integral part of all pregnancy counseling of women with SLE. Overall, studies suggest that there is unacceptable morbidity and mortality. A major clue to defining the pathogenesis of antibody-mediated damage is the selective vulnerability of the fetal heart. Vulnerability could relate to a direct or indirect antigen target differentially expressed in the developing human heart. Alternatively, biologic events operative during fetal life, such as apoptosis, could facilitate accessibility of intracellular antigens to the extracellular environment. Opsonization of apoptotic cardiocytes might promote an inflammatory/fibrosing cascade leading to tissue injury. A reproducible murine model of congenital heart block (CHB) would be a critical tool to define antibody pathogenicity at the histologic and molecular level with subsequent application for testing prophylactic and therapeutic interventions. The reporting of recurrence rates, mortality and morbidity, and maternal outcomes in a large number of patients has greatly facilitated family planning. The genetic contributions to disease may offer further insights.
Neonatal lupus erythematosus infants and their mothers: A 10-year retrospective study
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Neonatal lupus erythematosus (NLE) is a rare disease associated with transplacental transfer of maternal anti-Ro/anti-Sjögren syndrome A antibodies. The most common manifestations are cutaneous erythema and congenital heart block. Mothers of infants with NLE are either asymptomatic or diagnosed with autoimmune disease. The goal of this study is to investigate the clinical manifestation, prognosis, and association with autoimmune disease in NLE babies and their mothers in Taiwan.
Medical records of newborns with NLE and their mothers from two hospitals in Taiwan between January 1999 and January 2009 were reviewed. Twenty-five newborns (one set of twins) and 24 mothers of infants with NLE were included in the study. Clinical data, including characteristics of skin manifestations, the onset of symptoms, and infants' antibody titers, were collected. A diagnosis of NLE was made if the baby had heart block or characteristic skin lesions and maternal antibodies to Sjögren syndrome A/Ro, Sjögren syndrome B/La, or U1 ribonucleoproteins. Questionnaires were used to determine the mother's health status at the time of delivery and in subsequent years.
Of the infants, 84% had typical cutaneous manifestations of NLE, and 16% presented with congenital heart block without skin changes. The cutaneous lesions appeared on average at 21.7 weeks. Thirteen mothers were initially asymptomatic, and the other 11 remained asymptomatic over a mean follow-up period of 3.9 years. Two mothers developed lupus nephritis.
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Clinical studyThe health of mothers of children with cutaneous neonatal lupus erythematosus differs from that of mothers of children with congenital heart block

Abstract

Section snippets

Patients

Results

Discussion

J Am Acad Dermatol

J Invest Dermatol

Am J Med

Baillieres Clin Rheumatol

J Autoimmun

J Am Coll Cardiol

J Am Acad Dermatol

Eur J Obstet Gynecol Reprod Biol

Sur une maladie infantile et familiale caracterisee et la aort subite

Arch Med Enfants

Congenital heart blockreview of the literature. Report of a case with incomplete heterotaxy: the electrocardiogram in dextrocardia

Am J Dis Child

Possible discoid lupus erythematosus in a newborn infant

Arch Dermatol

Neonatal lupus erythematosus. A clinical, serological and immunologenetic study with review of the literature

Medicine

Neonatal lupus erythematosus

J Invest Dermatol

Neonatal lupus erythematosusa transplacentally acquired autoimmune disorder

Semin Dermatol

Neonatal lupus and the pathogenesis of cutaneous lupus

Pediatr Dermatol

The neonatal lupus syndrome

Clin Exp Rheumatol

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

Autoantibody responses to the ‘native’ 52-kDa SS-A/Ro protein in neonatal lupus syndromes, systemic lupus erythematosus, and Sjögren’s syndrome

J Immunol

Anti-La (SS-B) but not anti-Ro52 (SS-A) antibodies cross-react with laminin—a role in the pathogenesis of congenital heart block?

Clin Exp Immunol

Autoantibody response to the Ro/La particle may predict outcome in neonatal lupus erythematosus

Clin Exp Immunol

Clinical study
The health of mothers of children with cutaneous neonatal lupus erythematosus differs from that of mothers of children with congenital heart block