What is neonatal lupus?

Neonatal Lupus Erythematosus

Neonatal lupus erythematosus (NLE) is a rare acquired autoimmune disorder caused by the transplacental passage of maternal autoantibodies (primarily anti-Ro/SSA and anti-La/SSB) that can affect multiple organ systems in the fetus and newborn, with cardiac manifestations being the most serious. 1

Definition and Pathophysiology

Neonatal lupus occurs when maternal autoantibodies cross the placenta and target fetal tissues. The key features include:

• Caused primarily by maternal anti-Ro/SSA and/or anti-La/SSB antibodies 1
• Less commonly associated with anti-U1 ribonuclear protein (RNP) antibodies 2
• Affects approximately 2% of pregnancies in mothers with these antibodies who have not had a previous child with NLE 3
• Risk increases 10-fold (to 13-18%) in mothers who have previously had a child with NLE 1, 3

Clinical Manifestations

Cardiac Manifestations

• Complete heart block (CHB): The most serious manifestation

  • Occurs in ~2% of pregnancies with anti-Ro/SSA and/or anti-La/SSB antibodies 1
  • Typically develops between 16-26 weeks gestation 1
  • Irreversible once established 4
  • Associated with 20% mortality in utero or within the first year of life 1
  • More than 50% of affected children will require a pacemaker 1

• Other cardiac manifestations:

  • Cardiomyopathy (can occur with or without heart block) 4
  • Endocardial fibroelastosis 4
  • Myocardial dysfunction (rare presentation without heart block) 5

Cutaneous Manifestations

• Skin lesions resembling those seen in systemic lupus erythematosus 3
• May be present at birth but more commonly develop within the first few weeks of life 4
• Most common on face and scalp, often in a periorbital distribution 4
• Affect approximately 10% of infants born to mothers with anti-Ro/SSA antibodies 1
• Self-limited and typically resolve within weeks to months without scarring 4

Other Manifestations

• Hepatobiliary disease (10% of cases) 4:

  • Liver failure occurring at birth or in utero
  • Transient conjugated hyperbilirubinemia
  • Transient transaminase elevations

• Hematologic abnormalities (10% of cases) 4:

  • Thrombocytopenia
  • Neutropenia
  • Anemia

• Transient cytopenias (20% of cases) 1

• Mild transient transaminitis (30% of cases) 1

Diagnosis

The diagnosis of NLE is based on:

1. Presence of compatible clinical manifestations in the fetus or newborn
2. Detection of maternal autoantibodies (anti-Ro/SSA and/or anti-La/SSB)
3. Exclusion of other causes for the clinical findings

Monitoring and Management

Prenatal Monitoring

• Fetal echocardiography is recommended for pregnant women with anti-Ro/SSA and/or anti-La/SSB antibodies:
  • For women with no history of a child with CHB or NLE: serial fetal echocardiography starting between 16-18 weeks and continuing through week 26 1
  • For women with a prior infant with CHB or other NLE: weekly fetal echocardiography from weeks 16-18 through week 26 1

Management of Affected Infants

• Multidisciplinary approach at a tertiary care center is recommended 6

• Cardiac manifestations:

  • CHB is irreversible and often requires pacemaker placement 1
  • Management of CHB transfers to pediatric cardiologists 1

• Cutaneous manifestations:

  • Generally self-limited and resolve with clearance of maternal antibodies 3
  • Photoprotection is recommended

• Hepatic and hematologic manifestations:

  • Usually transient and resolve with clearance of maternal antibodies 1
  • Supportive care as needed

Long-term Outcomes and Follow-up

• Most non-cardiac manifestations are transient and resolve with clearance of maternal antibodies (usually by 6-8 months of age) 1, 4
• Some children who had NLE may develop other autoimmune diseases later in childhood 4
• Long-term follow-up is recommended, especially for those with cardiac involvement

Important Distinctions

• NLE associated with anti-RNP antibodies appears to have manifestations limited to the skin with no reported cardiac involvement 2
• Higher titers of anti-Ro/SSA antibodies are associated with greater risk of CHB 1

Maternal Implications

• About half of mothers are asymptomatic at the time of diagnosis of NLE in their child 4
• Some of these women eventually develop symptoms of autoimmune disease 4
• All mothers of affected infants should be evaluated for underlying autoimmune conditions