Neonatal and Pediatric Lupus Erythematosus
- Author: Jeffrey P Callen, MD; Chief Editor: Lawrence K Jung, MD more...
Background
This article discusses neonatal and pediatric lupus erythematosus (NLE) as well as cutaneous lupus erythematosus (LE) in children and adolescents. Specifically, NLE, which usually manifests as nonscarring, non–atrophy-producing lesions known as subacute cutaneous LE (SCLE), and cutaneous lesions of lupus erythematosus in children and adolescents, as well as the relationship of these lesions to systemic disease, will be reviewed (see the following image).
Neonatal lupus erythematosus. See also Pediatric Systemic Lupus Erythematosus, Systemic Lupus Erythematosus and Pregnancy, Lupus Nephritis, Bullous Systemic Lupus Erythematosus (BSLE), Acute Cutaneous Lupus Erythematosus (ACLE), and Physical Medicine and Rehabilitation for Systemic Lupus Erythematosus.
Etiology and Pathophysiology
Lupus erythematosus (LE) is a rare condition in children; most cases take the form of systemic lupus erythematosus (SLE). Neonatal lupus erythematosus (NLE) is thought to be caused by the transplacental passage of maternal autoantibodies; however, 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, central nervous system, or splenic abnormalities.
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 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 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.[1] 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 incidence of congenital heart block is 15-30% in infants with neonatal lupus erythematosus.
However, only some neonates exposed to these antibodies develop complications; therefore, other factors must be involved. These may include genetic predisposition, viral infection, and other unknown factors. The risk of neonatal lupus erythematosus or congenital heart block developing in a woman who tests positive for Ro/SSA who has never had a child with neonatal lupus erythematosus or congenital heart block is less than 1%, whereas the risk for a mother who has had an affected infant is roughly 25%. The cause of lupus erythematosus in children and adolescents is unknown, but, again, genetic predisposition is likely.
In one study, serum IgG from the mother of a neonate with congenital heart block inhibited L-type calcium channels in a rat heart model.[2] Additionally, induction of apoptosis in cultured cardiocytes has been demonstrated to result in the expression of Ro/La antigens on the cell surface. However, the antibodies associated with heart block and with cutaneous disease are believed to be different, with the Ro (SSA) against the 52/60-kd protein associated with heart block, and the La (SSB) against the 50-kd protein associated with cutaneous disease.
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.
Drugs, in particular minocycline, may be responsible for drug-induced systemic lupuslike disease among adolescents treated for acne vulgaris.
Epidemiology
Neonatal lupus erythematosus occurs in 1 of every 20,000 US live births. Lupus erythematosus of childhood occurs in 0.6 of every 100,000 children annually.
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.
Although no racial predilection has been observed, lupus erythematosus of childhood appears to be more common in black, Latin American, and Asian children (3:1 ratio in all races compared with white patients).
Neonatal lupus erythematosus of the heart affects girls more often than boys (female-to-male ratio of 2:1), and cutaneous neonatal lupus erythematosus also affects girls more often than boys (female-to-male ratio of 3:1). Prepubertal female-to-male ratios have been reported to be between 1:1 and 3:1, whereas the ratio in postpubertal children is between 8:1 and 10:1.
Neonatal lupus erythematosus affects children aged 0-6 months, whereas lupus erythematosus of childhood affects prepubertal and postpubertal children.
Prognosis
Neonatal lupus erythematosus (NLE) has significant associated morbidity and mortality when the heart is affected. In patients with cardiac involvement, neonatal lupus erythematosus may manifest as complete or incomplete congenital heart block. Heart block is evident in utero or at birth. The neonatal mortality rate is 20-30%. In children who are severely affected, a pacemaker is frequently needed, because sudden death or heart failure may occur. However, many children with congenital heart block may be relatively asymptomatic until adolescence, when they begin to exercise. At this time, they may develop syncope and require a pacemaker implantation.
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.
Most patients with neonatal lupus erythematosus of the skin, liver, or blood have transient disease that spontaneously resolves within 4-6 months. Skin and hematologic manifestations usually improve with the disappearance of maternal autoantibodies. In some cases, severe liver failure may occur and is associated with a poor prognosis, and death due to hepatitis may occur. Although cytopenia is self-limited, if severe thrombocytopenia is present, bleeding can affect the prognosis. Children rarely develop systemic lupus erythematosus (SLE) later in life. Siblings of affected individuals also have a risk of developing SLE later in life.
Morbidity and mortality of SLE of childhood depend on the organ systems affected. If the kidneys are affected, renal failure may occur. Joint disease does not lead to deformity but may be debilitating. Disease of the skin may lead to scar formation; however, in isolation, it is associated with a good prognosis.
Central nervous system abnormalities in neonatal lupus erythematosus are usually transient; however, whether long-term sequelae will result is unclear.[3]
Patient Education
Assess and educate the parent or caregiver about follow-up care for a child with neonatal lupus erythematosus (NLE) and the potential effects on subsequent pregnancies in the mother. In mothers who are asymptomatic at the time of delivery of a neonate with cutaneous neonatal lupus erythematosus or congenital heart block, assess for the future development of lupus erythematosus or another collagen vascular disease.
Patients with skin disease should restrict their sun exposure. Instruct patients about sun avoidance, use of protective clothing, and proper use of sunscreens and topical corticosteroids.
Although no specific diet is recommended, limit activity only if the disease is active, and base restrictions on the patient's abilities.
For patient education information, see Lupus (Systemic Lupus Erythematosus).
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