Neonatal lupus erythematosus
Synonyms and keywords: NL; NLE; NLS; neonatal lupus; neonatal lupus syndrome; neonatal systemic lupus erythematosus

# Overview
Neonatal lupus is a passively transferred autoimmune disease.  It occurs in about 1 to 2 percent of babies born to mothers with autoimmune disease, primarily systemic lupus erythematosus (SLE) and Sjogrens syndrome, and antibodies to SSA/Ro and/or SSB/La.  The most serious complication of neonatal lupus is complete heart block.

# Historical Perspective
The first case reported by Aylward in 1928, who described two siblings with complete heart block born to a mother who had Sjogrens syndrome.  Plant and Stevens described complete heart block as a manifestation of neonatal lupus in 1945.  But the first report linking autoimmune disease in a mother with cutaneous lupus was McCuistion and Schoch in 1954. In 1957 Hogg noted the possible relation between autoimmune disease of the mother and congenital heart block in her child. Finally in 1980 Weston reported the association of neonatal lupus with maternal anti-Ro autoantibodies.

# Pathophysiology
Neonatal lupus is presumed to result from transplacental passage of maternal anti-SSA/Ro and/or anti-SSB/La antibodies. Ro and La molecules are thought to form a single particle that is present in all cells.  Recent studies have investigated a potential role of naturally acquired fetal and maternal microchimerism in autoimmune diseases, including neonatal lupus.  Cell transfer between mother and fetus during pregnancy has recently been found to result in long-term persistence of fetal cells (fetal microchimerism) in the mother and maternal cells in her progeny (maternal microchimerism).  Another study described identification and characterization of maternal microchimerism in the heart of male infants with neonatal lupus syndrome who died from congenital heart block.

## Genetics
Genetic factors in the infant, in particular the HLA alleles DQB102, DRB103, and a polymorphism in the promoter region of the gene for tumor necrosis factor alpha (-308A, associated with higher TNF alpha production) may play a role in skin disease.

# Causes
Neonatal lupus is caused by maternal antibodies that cross the placenta, is responsible for 60 to 90 percent of cases of congenital complete heart block overall.
- Maternal antibodies to SSA/Ro and/or SSB/La
- Maternal antibodies to other antigens, as an example, anti-U1 RNP antibodies in the absence of anti-SSA/Ro or anti-SSB/La antibodies were found in a few instances.
- Recent studies have investigated a potential role of naturally acquired fetal and maternal microchimerism in autoimmune diseases, including neonatal lupus. Cell transfer between mother and fetus during pregnancy has been found to result in long-term persistence of fetal cells (fetal microchimerism) in the mother and maternal cells in her progeny (maternal microchimerism).

# Differentiating Neonatal Lupus Erythematosus from other Diseases
In patients without neonatal lupus or significant congenital structural heart disease, familial inheritance of conduction disease is often responsible for AV block.

# Epidemiology and Demographics
The prevalence of Anti-SSA antibodies in women is 1:200 while the incidence of neonatal lupus is only 1 in 20,000 live births. Only 1-2% of the infants of mothers with anti-SSA/Ro with or without anti-SSB/La antibodies develop neonatal lupus, although it ranges from 0.6% to 25% with an average of 7.2% by various studies. The incidence increases to 3% if the mother has anti-La antibodies in addition to anti-Ra antibodies. If the mother has also SLE along with anti-SSA antibodies the incidence of NLE may be up to 6-13%. This is much higher and reaches up to 25% if the mother already had a child with neonatal lupus. 15-20% present as complete heart block and 6% present as cutaneous lupus.  The incidence of congenital heart block is seen in 50-60% while the cutaneous lupus is seen in 25-30% and the combination of cutaneous and cardiac manifestations seen only in 4-10% of the patients with neonatal lupus.

# Risk Factors
Presence of maternal antibodies to SSA/Ro and/or SSB/La is the most powerful risk factor for congenital heart block.  Other factors include Maternal anti-U1 RNP antibodies. Fetal and genetic factors have also been identified.

# Screening
Prenatal screening for anti-SSA/Ro and anti-SSB/La antibodies is warranted for women who are known to be at risk.  Women who are more likely to have anti-SSA/Ro and anti-SSB/La antibodies include those with lupus, Sjogren's syndrome, an undifferentiated autoimmune disease, or having a baby with neonatal lupus in a previous pregnancy.

# Natural History, Complications and Prognosis
The rash of neonatal lupus generally does not cause scarring and disappears within six to eight months. Appearance of skin lesions postnatally is independent of breastfeeding. Thus, breastfeeding is not contraindicated in mothers with anti-SSA/Ro and/or anti-SSB/La antibodies.  Infants and young children with complete heart block who are asymptomatic usually remain well until later childhood, adolescence, or adulthood. However, exercise limitation and even death are possible in the absence of pacing. The prognosis following pacemaker implantation is excellent for most children, although development of heart failure may occur.

# Diagnosis
Women who test positive for SSA/Ro and SSB/La autoantibodies may benefit from more intensive assessment for fetal heart block with frequent fetal echocardiographic testing during pregnancy. Complete heart block (and usually second degree AV block) results in fetal bradycardia that can be detected by routine fetal auscultation, ultrasonography, or echocardiography.

# Treatment

## Medical Therapy
- Prenatal treatment with fluorinated glucocorticoids is suggested for mothers of fetuses with second degree heart block, through the end of pregnancy depending upon the response.
- Expert suggestions recommend preemptive treatment with hydroxychloroquine (400 mg orally once a day) in pregnant women with anti-SSA/Ro antibodies who have previously given birth to a child with cardiac manifestations of neonatal lupus regardless of maternal health status.

## Surgery
The principal therapeutic decision after the immediate perinatal period involves the need for pacemaker placement.