AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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 NLE. 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 NLE may later develop an atypical rather than classic picture of systemic lupus erythematosus (SLE) or other connective tissue disorder. If a mother with anti-Ro autoantibodies has 1 child with NLE, the incidence in subsequent pregnancies is approximately 25%. The incidence of congenital heart block is 15-30% in infants with NLE.

The Medscape Lupus Resource Center may be of interest, as may the Medscape CME course Neonatal Emergencies.

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 NLE. These autoantibodies can be found alone or in combination; however, anti-Ro is present in almost 95% of patients. Mothers of patients with NLE may have defined or undifferentiated autoimmune disorders, such as SLE, 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 NLE 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. 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 NLE 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

NLE 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 NLE 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

NLE has been reported slightly more often in female infants than in male infants.

Age

The onset of NLE occurs between birth and a few months of life.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Many seropositive mothers with anti-SSA and anti-SSB antibodies give birth to infants who do not show signs and symptoms of NLE. Mothers of children with NLE have been most commonly diagnosed with SLE; however, occasionally another diagnosis, such as mixed connective-tissue disease or leukocytoclastic vasculitis, has been rendered.¹

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.¹
• • Two thirds of patients with the skin findings have them at birth, with the remainder developing them within the first 2-5 months of life.
  • In some infants, solar exposure seems to precipitate the eruption. 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 NLE, 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 NLE should be evaluated for hematologic, hepatic, and cardiac involvement.
• Hydrocephalus and macrocephaly may be new manifestations of NLE.² 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 NLE, even if a suggestive maternal history is lacking.³

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 SS or UAS have a greater risk of delivering an infant with congenital complete heart block than those with SLE.
  • 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 NLE.
• Mothers of patients with NLE may have defined or undifferentiated autoimmune disorders, such as SLE, SS, UAS, or RA.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

At birth, the 4 main considerations in the differential diagnosis are usually congenital rubella, congenital syphilis, Bloom syndrome, and Rothmund-Thomson syndrome. Later, slightly atrophic vascular patches may resemble other disorders, including lymphangiomas.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Screen maternal serum for antinuclear, anti–double-stranded DNA, anti-SSA/Ro, anti-SSB/La, and anti–U1-RNP antibodies.
• • Despite being positive for Ro and/or La antibodies, many mothers may be healthy and without clinical symptoms during pregnancy.
  • Closely monitor mothers in whom SLE is diagnosed by clinical symptoms and laboratory test results.
• Check neonatal serum for anti-SSA/Ro, anti-SSB/La, and anti–U1-RNP antibodies. These maternal autoantibodies that cross the placenta can react with various fetal tissues causing an increased risk of acquiring NLE.
• Perform a complete blood count with platelets. The blood panel may reveal pancytopenia, thrombocytopenia, or leukopenia with a hemolytic anemia.
• Perform liver function tests. Hepatomegaly with an elevated transaminase level may be observed.

Imaging Studies

• Frequent ultrasonographic monitoring of the fetal heart rate during pregnancy is recommended in women with autoimmune disorders.
• Electrocardiography and 24-hour Holter monitoring may reveal various cardiac conduction disorders, which lead to different types of heart blocks.
• Echocardiography may reveal various types of structural deformities in the heart.

Histologic Findings

A skin biopsy specimen shows moderate hyperkeratosis, follicular plugging, and vacuolar degeneration in the basal cell layer. An immunofluorescent examination reveals a granular deposition of IgG at the dermoepidermal junction; immunoglobulin M (IgM) and C3 deposition may also be evident.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• The type of treatment and the long-term prognosis for neonates with cardiac rhythm and conduction disturbances depends on the presence of underlying congenital heart abnormalities.
• Treatment of skin lesions includes mild steroids and, possibly, laser treatment for residual telangiectasia.
• Photoprotection is highly desirable because solar exposure may precipitate skin lesions.

Surgical Care

In severe cases, surgical implantation of a pacemaker, along with the correction of structural abnormalities in the heart, may be necessary.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Congenital heart block, an important manifestation of neonatal lupus syndrome that carries a poor prognosis, may merit preventive therapy in pregnancy during fetal cardiac development.⁴ It should be considered in pregnant women with systemic lupus erythematosus who are anti-SSA/Ro antibody positive and have previous children with congenital heart block.

A general management plan of pregnancy in mothers with systemic lupus erythematosus includes treatment of disease flares using drugs that are effective but also safe for the fetus.⁵ Such an approach may diminish or reduce the prevalence of complete heart block associated with NLE. Corticosteroids and some immunosuppressive drugs are sometimes used, but long-term outcome data in children exposed to immunosuppressive drugs in utero is lacking.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Children with NLE need continued follow-up, especially prior to adolescence and if the mother herself has an autoimmune disease.⁶ Although the child may not be at increased risk of developing SLE, the development of some form of autoimmune disease in early childhood may be of concern.

Further Outpatient Care

• Observe mothers with positive autoantibodies and/or mothers who give birth to a child with NLE.
• Monitor subsequent pregnancies with serial ultrasonography and echocardiography.

Prognosis

• The presence of cardiac abnormalities is associated with congestive heart failure and early placement of a pacemaker. The neonatal mortality rate is 20-30%.
• Skin and hematologic manifestations usually improve with the disappearance of maternal autoantibodies.
• The outcome for children with hepatobiliary diseases is generally good. In some cases, severe liver failure may occur and is associated with a poor prognosis.
• Central nervous system abnormalities in NLE are usually transient; whether long-term sequelae will result is unclear.³

Patient Education

• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lupus (Systemic Lupus Erythematosus).

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• The mother of a child with NLE should be aware that the risk of recurrence in future pregnancies is about 25%.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Apr 18, 2008