eMedicine Specialties > Dermatology > Connective Tissue Diseases

Neonatal Lupus Erythematosus

Author: Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Jack Grzybowski, MD, Staff Physician, Department of Pediatrics, UMDNJ-New Jersey Medical School
Contributor Information and Disclosures

Updated: Jul 16, 2009

Introduction

Background

Neonatal lupus erythematosus (NLE) is a rare disorder caused by the transplacental passage of maternal autoantibodies. Only 1% of infants with positive maternal autoantibodies develop neonatal lupus erythematosus. The most common clinical manifestations are cardiac, dermatologic, and hepatic. Some infants may also have hematologic abnormalities.

Most mothers at the time of childbirth are healthy and without signs or symptoms of lupus erythematosus or other collagen-vascular disorders. Mothers of children with neonatal lupus erythematosus may later develop an atypical rather than classic picture of systemic lupus erythematosus (SLE) or other connective-tissue disorder.¹ If a mother with anti-Ro autoantibodies has 1 child with neonatal lupus erythematosus, the incidence in subsequent pregnancies is approximately 25%. The incidence of congenital heart block is 15-30% in infants with neonatal lupus erythematosus.

Pathophysiology

The mother produces immunoglobulin G (IgG) autoantibodies against Ro (SSA), La (SSB), and/or U1-ribonucleoprotein (U1-RNP), and they are passively transported across the placenta. The presence of maternal anti-SSA/Ro and anti-SSB/La antibodies increases the risk of bearing infants with neonatal lupus erythematosus. These autoantibodies can be found alone or in combination; however, anti-Ro is present in almost 95% of patients. Mothers of patients with neonatal lupus erythematosus may have defined or undifferentiated autoimmune disorders, such as systemic lupus erythematosus, Sjögren syndrome (SS), undifferentiated autoimmune syndrome (UAS), or rheumatoid arthritis (RA).

The 52-kd SSA/Ro (Ro52) ribonucleoprotein is an antigenic target strongly linked with the autoimmune response in mothers whose children have neonatal lupus erythematosus and cardiac conduction disturbances, mainly congenital heart block. Anti-SSA/Ro52 autoantibodies recognize the Ro52 protein cardiac 5-HT4 serotoninergic receptor and inhibit serotonin activated L-type calcium currents (ICa). This effect could explain the pathogenesis of the cardiac rhythm disturbances, which lead to an increased risk of diminished cardiac output and the subsequent development of congestive heart failure.² However, these conduction defects are caused not only by Ro antibodies but also by anti-SSB/La antibodies and other autoantibodies against cardiac adrenoceptors and muscarinic acetylcholine receptors.

The skin manifestations of neonatal lupus erythematosus occur in the first month or later in life and are mainly due to the presence of anti-SSB/La antibodies, but they may be mediated by other antibodies. Most infants have cardiac and dermatologic manifestations, but some of them may also have hematologic and liver involvement.

Frequency

International

Neonatal lupus erythematosus is an uncommon disease described mainly in isolated case reports. The presence of human leukocyte antigen B8 (HLA-B8) and human leukocyte antigen DR3 (HLA-DR3) in the mother predisposes the infant to neonatal lupus erythematosus and congenital heart block.

Mortality/Morbidity

Congenital heart block can result in congestive heart failure and subsequent placement of a pacemaker. In one investigation, 57% of patients eventually required a pacemaker. Congenital heart block is associated with a 20-30% mortality rate in the neonatal period. Deaths may also occur later in life as a result of the failure of the pacemaker.

Sex

Neonatal lupus erythematosus has been reported slightly more often in female infants than in male infants.

Age

The onset of neonatal lupus erythematosus occurs between birth and a few months of life.

Clinical

History

Many seropositive mothers with anti-SSA and anti-SSB antibodies give birth to infants who do not show signs and symptoms of neonatal lupus erythematosus. Mothers of children with neonatal lupus erythematosus have been most commonly diagnosed with systemic lupus erythematosus; however, occasionally another diagnosis, such as mixed connective-tissue disease or leukocytoclastic vasculitis, has been rendered.³

Circulating fetal blood antibodies, which have been passively acquired, can lead to permanent heart disease and transient cutaneous manifestations. Hematologic and hepatic abnormalities may also occur.

• The cutaneous findings are transient and resemble those of subacute cutaneous lupus erythematosus. They may be urticarialike and desquamative, occasionally with ulceration.^3,4
  • Two thirds of patients with the skin findings have them at birth,⁵ with the remainder developing them within the first 2-5 months of life.
  • In some infants, solar exposure seems to precipitate the eruption, although UV light may not be responsible.⁶ The eruptions usually disappear when maternal antibodies are absent in the neonatal circulation at about the sixth month of life.
• Cardiac rhythm abnormalities and conduction defects may be observed in various forms, but the occurrence of congenital complete heart block is most closely related to neonatal lupus erythematosus, with an incidence of 15-30%. Cardiac blocks usually develop in utero between the 18th and 20th weeks of pregnancy.
• Hematologic disturbances (eg, hemolytic anemia, profound thrombocytopenia, neutropenia) may occur in the first 2 weeks of life. Hematologic symptoms may vary from benign to severe and usually appear at around the second week of life and disappear by the end of the second month.
• The clinical picture of hepatobiliary diseases may vary from mild elevations of aminotransferase levels to conjugated hyperbilirubinemia with normal or slightly elevated aminotransferase levels.
• In children selected because of cutaneous involvement, thrombocytopenia and hepatic disease may be as common as cardiac disease, and these diseases occur more often in male babies with crusted plaques than in female babies. Thus, children with cutaneous neonatal lupus erythematosus should be evaluated for hematologic, hepatic, and cardiac involvement.
• Hydrocephalus and macrocephaly may be new manifestations of neonatal lupus erythematosus.⁷ Infants born to mothers with anti-Ro antibodies should probably be monitored for hydrocephalus as part of their routine physical examination.
• In a neonate with congenital heart block or thrombocytopenia, serum autoantibodies should be investigated to rule out neonatal lupus erythematosus, even if a suggestive maternal history is lacking.⁸
• Neonatal lupus in triplets was described in a patient with undifferentiated connective-tissue disease evolving to systemic lupus erythematosus.⁹ The 3 newborns had only SSA positivity associated with asymptomatic transient neutropenia.

Physical

• Cutaneous findings
  • A well-demarcated erythematous, mild, scaling plaque that is often annular and appears predominately on the scalp, neck, or face is present. This plaque is typically periorbital in distribution. Similar plaques may appear on the trunk or extremities. They are sometimes crusted; this finding is observed more often in male babies than in female babies.
  • Follicular plugging is usually not evident.
  • Healing tends to occur within a year, with mild cutaneous atrophy, with or without associated telangiectasia. The atrophic telangiectatic changes are most evident near the temples and scalp. The latter site may be associated with a permanent alopecia.
  • At times, small angiomalike papulonodules may be seen.
• Cardiac findings
  • Mothers with primary Sjögren syndrome or undifferentiated autoimmune syndrome have a greater risk of delivering an infant with congenital complete heart block than those with systemic lupus erythematosus.¹⁰
  • Other disturbances may also be present. These disturbances lead to blocks in the atrioventricular or Purkinje systems, such as sinus bradycardia and prolongation of the QT interval. An irregular heartbeat may also be present.
  • In some cases, myocarditis and pericarditis can develop and lead to bradycardia.
• Hematologic findings
  • Autoantibodies, mainly anti-Ro, can bind directly to the neutrophil and cause neutropenia.
  • These findings may improve or disappear as maternal antibodies are metabolized.
• Hepatomegaly may be present.

Causes

• The mother produces autoantibodies against Ro (SSA), La (SSB), and/or U1-RNP, and they are passively transported across the placenta. The presence of maternal anti-SSA/Ro and anti-SSB/La antibodies increases the risk of bearing infants with neonatal lupus erythematosus.
• Mothers of patients with neonatal lupus erythematosus may have defined or undifferentiated autoimmune disorders, such as systemic lupus erythematosus, Sjögren syndrome, undifferentiated autoimmune syndrome, or rheumatoid arthritis.

• Search for CME/CE on This Topic »

• Atrioventricular Block, Second Degree (Pediatrics: Cardiac Disease and Critical Care Medicine)
• Neonatal Lupus and Cutaneous Lupus Erythematosus in Children (Pediatrics: General Medicine)

• Lupus (Systemic Lupus Erythematosus) Treatment
• Lupus (Systemic Lupus Erythematosus) Overview
• Lupus (Systemic Lupus Erythematosus) Causes
• Lupus (Systemic Lupus Erythematosus) Symptoms
• Blood and Lymphatic System Center

• Survival for Pediatric Rheumatology Patients Better Than Previously Reported
• Cutaneous Neonatal Lupus Predicts Cardiac Lupus in Subsequent Child

• Neonatal Medicine Resource Center
• Lupus Resource Center