Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis
- Jill P Buyon, MD
Jill P Buyon, MD
- Professor of Medicine
- New York University School of Medicine
- Section Editors
- Thomas JA Lehman, MD
Thomas JA Lehman, MD
- Section Editor — Pediatric Rheumatology
- Professor of Clinical Pediatrics
- Cornell University Medical College
- John K Triedman, MD
John K Triedman, MD
- Section Editor — Pediatric Cardiology
- Professor of Pediatrics
- Harvard Medical School
- Joseph A Garcia-Prats, MD
Joseph A Garcia-Prats, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
Neonatal lupus (NL) is an autoimmune disease that is passively transferred from the mother to the fetus. The major manifestations are cardiac and cutaneous findings. The most serious complication of NL is complete heart block (approximately 20 percent have an associated cardiomyopathy at the initial diagnosis or develop it later [1,2]). In this topic review, the cardiac manifestations of NL are referred to as cardiac-NL and can include any degree of block (referred to as congenital heart block [CHB]) that may or may not be accompanied by extranodal disease such as valvular abnormalities, endocardial fibroelastosis, and/or dilated cardiomyopathy. Occasionally, those manifestations may occur in the absence of heart block.
This topic reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of NL. The management and outcomes of NL are discussed in greater detail separately. Pregnancy in women with systemic lupus erythematosus (SLE) and diagnosis and management of fetal arrhythmias are also reviewed elsewhere. (See "Neonatal lupus: Management and outcomes" and "Pregnancy in women with systemic lupus erythematosus" and "Overview of the general approach to diagnosis and treatment of fetal arrhythmias".)
The cardiac manifestations of NL (cardiac-NL), which most commonly involve injury to the conduction system (congenital heart block [CHB]), with complete atrioventricular (AV) block being the most characteristic, occur in approximately 2 percent of offspring of women who have antibodies to Ro/SSA (Sjögren syndrome type A antigen) and/or La/SSB (Sjögren syndrome type B antigen) [3-8]. NL is responsible for 80 to 95 percent of all cases of congenital complete heart block in the absence of structural defects diagnosed in utero or in the neonatal period [9,10]. NL is a much less common cause of heart block presenting after the neonatal period (5 percent in one study) . The risk of developing cutaneous manifestations of NL is 7 to 16 percent in offspring of anti-Ro- and anti-La-positive mothers [5,7] but is also sometimes associated with antibodies to ribonucleoprotein (RNP) .
NL is associated with these specific autoantibodies (Ro/SSA, La/SSB) independent of maternal disease. While some mothers may have systemic lupus erythematosus (SLE) and/or Sjögren syndrome, in many other cases, the mother is totally asymptomatic . Approximately one-half of mothers with these autoantibodies who do not have other evidence of autoimmune disease at the time of the baby's birth later develop autoimmune disease (more commonly Sjögren syndrome than SLE) . (See 'Pathogenesis' below.)
The prevalence of anti-Ro/SSA antibodies was initially reported as 0.2 to 0.72 percent in female blood donors  and, more recently, as 0.86 percent in healthy females in the general population (this may be an underestimation since a less reliable test for anti-Ro/SSA was used for initial screening) . For patients with SLE, the estimated prevalence of this antibody is 40 percent  and in those with SS between 60 to 100 percent . The population prevalence of CHB in Finland was reported as 1 in 17,000 live births , with the highest annual estimate at 1:6500. However, this may be an underestimation since only children with pacemakers were included and fetal deaths were not captured. If the true prevalence of anti-Ro/SSA approaches 0.9 percent and CHB occurs in 2 percent and recurs in 18 percent, this could yield approximately 600 to 700 cases per year in the United States based upon the 2012 National Vital Statistics System data of 3,952,841 births. These results are consistent with a crude estimate based upon the 0.5 percent prevalence of anti-Ro/SSA antibodies in asymptomatic pregnant women and the rate of CHB of 1 in 15,000 to 1 in 22,000 livebirths [17,18].
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- Other factors
- CLINICAL MANIFESTATIONS
- Heart block
- Other cardiac abnormalities
- Other manifestations
- SCREENING AND SURVEILLANCE
- - Maternal screening
- - Fetal surveillance for heart block
- Postnatal testing
- DIFFERENTIAL DIAGNOSIS
- Rash without heart block
- Fetal bradycardia/heart block
- SUMMARY AND RECOMMENDATIONS