Neonatal and Pediatric Lupus Erythematosus

Updated: Jun 08, 2016
  • Author: Alisa N Femia, MD; Chief Editor: Lawrence K Jung, MD  more...
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Overview

Background

This article discusses neonatal lupus erythematosus (NLE) (see the image below) and cutaneous lupus erythematosus (LE) in children and adolescents. NLE usually manifests as nonscarring, non–atrophy-producing lesions similar to subacute cutaneous LE (SCLE). In this article, the cutaneous manifestations of NLE, as well as the relationship of these lesions to systemic disease is reviewed.

Neonatal lupus erythematosus. 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.

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Etiology and Pathophysiology

Lupus erythematosus (LE) is a rare condition in children; most cases take the form of systemic lupus erythematosus (SLE). However, cutaneous lupus erythematosus (CLE) does rarely occur in childhood and takes the form of chronic CLE (CCLE), subacute CLE (SCLE), or acute CLE (ACLE). Of these subtypes, CCLE is the most common in childhood. [1] The pathogenesis of LE in childhood is not well-described, but it is thought to be the result of a combination of environmental and genetic factors. Drug-induced cases of childhood LE, especially as a result of minocycline or antitumor necrosis factor-α agents, have also been described. [2, 3]

Neonatal lupus erythematosus (NLE) is thought to be caused by the transplacental passage of maternal autoantibodies; however, only 1-2% of infants with positive maternal autoantibodies develop neonatal lupus erythematosus. The most common clinical manifestations are dermatologic, cardiac, 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 NLE; rarely, NLE is due to maternal passage of U1-RNP antibodies. 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, undifferentiated autoimmune syndrome, or rheumatoid arthritis.

A case report describes a case of cutaneous NLE involving an infant conceived through in vitro fertilization with a healthy oocyte donor and a gestational mother with Sjögren syndrome (SS). This case demonstrates that direct inheritance of genetic susceptibility from a mother afflicted with autoimmunity is not required for NLE. [4]

Serum containing anti-SSA/Ro antibodies recognizes either the 52- or 60-kd protein from the Ro-RNP complex. [5] 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. [6] In addition, 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. [7]

Furthermore, induction of apoptosis in cultured cardiocytes has been demonstrated to result in the expression of Ro/La antigens on the cell surface, and recent studies have demonstrated that plasmin generation as a result of the interaction of anti-SSA/Ro antibodies with apoptotic cardiocytes is involved in the pathogenesis of cardiac NLE. [8, 9]

However, these conduction defects are caused not only by Ro antibodies but also by antibodies to SSB/La, a phosphoprotein that associates with the Ro-RNP complex, [10] along with other autoantibodies against cardiac adrenoreceptors and muscarinic acetylcholine receptors. 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 and U1-RNP antibodies associated with cutaneous disease.

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 presence of human leukocyte antigen (HLA)–B8 and HLA-DR3 in the mother may predispose the infant to NLE and congenital heart block. In addition, recently, HLA-DRB1*04 and HLA-Cw*05 have been found to confer susceptibility to anti-SSA/Ro–mediated congenital heart block, while HLA-DRB1*13 and HLA-Cw*06 have been identified as protective alleles. In addition, transmission of paternal HLA-DRB1*04 was associated with congenital heart block. [11]

The incidence of congenital heart block in infants with NLE is 15-30%. The risk of NLE or congenital heart block developing in an infant of a woman who tests positive for Ro/SSA who has previously never had a child with NLE or congenital heart block is less than 1%, whereas the risk in an infant of a mother who has had an affected child is roughly 15-25%. The cause of LE in children and adolescents is unknown, but, again, genetic predisposition is likely.

The skin manifestations of NLE occur in the first month of life or soon thereafter and are mainly due to the presence of anti-SSB/La antibodies; however, they may be mediated by other antibodies.

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Epidemiology

Neonatal lupus erythematosus (NLE) occurs in 1 of every 20,000 US live births. Lupus erythematosus (LE) of childhood occurs in 0.6-2.2 of every 100,000 children annually.

Although no racial predilection has been observed, LE of childhood appears to be more common in black, Latino, and Asian children (3:1 ratio in all races compared with white patients).

NLE of the heart affects girls more often than boys (female-to-male ratio of 2:1), and cutaneous NLE also affects girls more often than boys (female-to-male ratio of 3:1). In terms of childhood cutaneous LE, 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. [1]

NLE affects children aged 0-6 months, whereas LE of childhood affects prepubertal and postpubertal children, with the majority of cases occurring in children younger than 10 years. [12]

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Prognosis

Although cutaneous, hematologic, and hepatic manifestations of neonatal lupus erythematosus (NLE) are transient, NLE has substantial associated morbidity and mortality, particularly when the heart is affected, which may occur in up to 65% of patients. [13]

Cardiac NLE may manifest as complete or incomplete congenital heart block. Heart block may be evident in utero, detected during the second or third trimester, but is often undiagnosed until birth. The neonatal mortality rate of those with cardiac NLE is 20-30%. In children who are severely affected, a pacemaker is frequently needed because sudden cardiac death or heart failure may occur. In one investigation, 57% of patients eventually required a pacemaker. 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 pacemaker implantation. Deaths may also occur later in life as a result of failure of the pacemaker.

Most patients with NLE of the skin, liver, or blood have transient disease that spontaneously resolves within 4-6 months. Central nervous system abnormalities in NLE are usually temporary as well; however, whether long-term sequelae result is unclear. [14] 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; death due to hepatitis may occur. Although cytopenias are self-limited, when 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 depends on the organ systems affected, and manifestations are highly variable. However, pediatric patients with SLE tend to have more fulminant disease presentations compared with adults, and they are prone to a greater degree of organ damage over time, resulting in 2- to 3-fold increases in mortality. [15, 16] If the kidneys are affected, renal failure may occur. Renal involvement is a major determinant of prognosis. 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.

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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 NLE or congenital heart block, assess for the future development of lupus erythematosus (LE) or another collagen-vascular disease in the mother. In addition, mothers who are known to be anti-SSA/Ro or anti-SSB/La positive should be counseled on the risk for NLE in their child, and they should have appropriate neonatal screening.

Patients with LE and NLE should restrict their sun exposure. Instruct parents and 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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