Lupus erythematosus (LE) is a condition that rarely occurs in children, most cases take the form of systemic lupus erythematosus (SLE). However, cutaneous lupus erythematosus (CLE) is not uncommon in childhood and takes the form of chronic CLE (CCLE), subacute CLE (SCLE), or acute CLE (ACLE). Of this subtype, CCLE is the most common in children. The pathogenesis of LE in childhood is not well explained, but is thought to be the result of a combination of environmental and genetic factors. Drug-induced cases of LE mass, mainly as a result of minocycline or antitumor necrosis factor-α agents.
Neonatal lupus erythematosus (NLE) is thought to be caused by the presence of a part, namely transplacental maternal autoantibodies but only 1-2% of infants with positive maternal autoantibodies develop neonatal lupus erythematosus. The most common clinical manifestations are skin, heart and liver. Some babies may also have hematology, central nervous system, or spleen 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 infants with less-bearing NLE, NLE is due to maternal share of U1-RNP antibodies. These autoantibodies can be found alone or in combination but anti-Ro is present in nearly 95% of patients. Maternal patients with NLE may have identified or differentiated autoimmune disorders, such as SLE, Sjögren’s syndrome, undifferentiated autoimmune syndrome, or rheumatoid arthritis.
Serum containing anti-SSA / Ro antibodies recognizes either the 52- or 60-kd protein of the Ro-RNP complex. The 52-kd SSA / Ro (Ro52) ribonucleoprotein is the target antigen strongly associated with the autoimmune response of mothers whose children have NLE and impaired cardiac conduction, especially congenital heart block. Anti-SSA / Ro52 autoantibodies recognize the cardiac protein Ro52 5-HT4 serotoninergic receptors and inhibit serotonin-active L-type calcium (ICA) flow. This effect could explain the pathogenesis of impaired heart rhythm, which leads to an increased risk of reduced cardiac output and the subsequent development of congestive heart failure.
Additionally, in one study, serum IgG from neonatal mothers with congenital heart block inhibited L-type calcium channels in a mouse model of heart. In addition, the induction of apoptosis in cardiocytes has been shown to produce the expression of Ro / La antigen on the cell surface, and recent studies have shown 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.
However, this conduction defect is caused not only by Ro antibodies but also by antibodies to SSB / La, a phosphoprotein associated with the Ro-RNP complex, with other autoantibodies on cardiac adrenoreceptors as well as muscarinic acetylcholine receptors. Antibodies associated with heart block and skin disease are believed to be different, with Ro (SSA) against the 52- / 60-kd protein associated with heart block and La (SSB) against the 50-kd protein and U1-RNP antibody associated with skin disease.
Only a few neonates exposed to these antibodies experience complications therefore, another factor must be involved. This may include genetic predisposition, viral infection, and other factors that are not known. 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 provide susceptibility to innate anti-SSA / Ro-mediated heart block, whereas HLA-DRB1 * 13 and HLA-Cw * 06 have been identified. as a protective allele. Additionally, paternal transmission of HLA-DRB1 * 04 is associated with congenital heart block.
The incidence of congenital heart block in infants with NLE is 15-30%. The risk for NLE or congenital heart block developing in an infant from a woman who tests positive for Ro / SSA who has previously had a child with NLE or congenital heart block is less than 1%, whereas the risk in infants of mothers who have had affected children is approximately 15-25%. The cause of LE in children and adolescents is unknown, but, again, a genetic predisposition is possible. The cutaneous manifestations of NLE occur in the first month of life or shortly thereafter and are mainly due to the presence of anti-SSB / La antibodies but may be mediated by other antibodies.
Neonatal lupus erythematosus (NLE) occurs in 1 in 20,000 US live births. Lupus erythematosus (LE) from childhood occurs in 0.6-2.2 out of every 100,000 children per year. Although no racial predilection has been observed, childhood LE appears to be more common in black, Latino, and Asian children (3: 1 ratio of all races compared to white patients).
Cardiac NLE affects girls more often than boys (female-to-male ratio 2: 1), and cutaneous NLE also affects girls more often than boys (female-to-male ratio 3: 1). In terms of LE skin, the prepubertal female-to-male ratio has been reported to be between 1: 1 and 3: 1, whereas the ratio in postpubertal children is between 8: 1 and 10.
NLE affects children 0-6 months of age, whereas LE of childhood affects prepubertal and postpubertal children, with the majority of cases occurring in children younger than 10 years.
Although the 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 can occur in up to 65% of patients.
Cardiac NLE can manifest as complete or incomplete congenital heart block. Heart blocks may be evident in the uterus, detectable during the second or third trimester, but often are not diagnosed until birth. The neonatal mortality rate of those with cardiac NLE is 20-30%. In children who are affected, a pacemaker is often needed because sudden cardiac death or heart failure can occur.
In one investigation, 57% of patients eventually needed a pacemaker. However, many children with congenital heart block may be relatively asymptomatic until adolescence, when they start exercising. At this time, they can develop syncope and require implantation of a pacemaker. Death can 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 resolves spontaneously in 4-6 months. Central nervous system disorders in NLE are usually temporary as well; However, whether long-term sequelae is unclear and the haematological manifestations usually improve with the loss of maternal autoantibodies. In some cases, severe liver failure may occur and is associated with a poor prognosis; death from hepatitis can occur. Although cytopenias are self-limited, when severe thrombocytopenia is present, bleeding can affect prognosis. Children rarely develop systemic lupus erythematosus (SLE) later in life. Siblings of the affected individual also have a risk of developing SLE at a later date.
The morbidity and mortality of childhood SLE depends on the organ system affected, and its manifestations vary widely. However, pediatric patients with SLE tend to have a more fulminant presentation of the disease than adults, and they are prone to greater levels of organ damage over time, resulting in a 2 to 3 fold increase in mortality. If the kidneys are affected, kidney failure can occur. Joint disease does not cause deformities but may be debilitating. Skin disease can lead to scar formation; However, in isolation, this is associated with a favorable prognosis.