Neonatal Systemic lupus erythematosus
Synonyms
2
Overview
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.
Symptoms
Many serpsitive mthers with anti-SSA and anti-SSB antibdies give birth t infants wh d nt shw signs and symptms f NLE. Mthers f children with NLE have been mst cmmnly diagnsed with SLE; hwever, ccasinally anther diagnsis, such as mixed cnnective-tissue disease r leukcytclastic vasculitis, has been rendered.1 Circulating fetal bld antibdies, which have been passively acquired, can lead t permanent heart disease and transient cutaneus manifestatins. Hematlgic and hepatic abnrmalities may als ccur. The cutaneus findings are transient and resemble thse f subacute cutaneus lupus erythematsus. They may be urticarialike and desquamative, ccasinally with ulceratin.1 Tw thirds f patients with the skin findings have them at birth, with the remainder develping them within the first 2-5 mnths f life. In sme infants, slar expsure seems t precipitate the eruptin. The eruptins usually disappear when maternal antibdies are absent in the nenatal circulatin at abut the sixth mnth f life. Cardiac rhythm abnrmalities and cnductin defects may be bserved in varius frms, but the ccurrence f cngenital cmplete heart blck is mst clsely related t NLE, with an incidence f 15-30%. Cardiac blcks usually develp in uter between the 18th and 20th weeks f pregnancy. Hematlgic disturbances (eg, hemlytic anemia, prfund thrmbcytpenia, neutrpenia) may ccur in the first 2 weeks f life. Hematlgic symptms may vary frm benign t severe and usually appear at arund the secnd week f life and disappear by the end f the secnd mnth. The clinical picture f hepatbiliary diseases may vary frm mild elevatins f amintransferase levels t cnjugated hyperbilirubinemia with nrmal r slightly elevated amintransferase levels. In children selected because f cutaneus invlvement, thrmbcytpenia and hepatic disease may be as cmmn as cardiac disease, and these diseases ccur mre ften in male babies with crusted plaques than in female babies. Thus, children with cutaneus NLE shuld be evaluated fr hematlgic, hepatic, and cardiac invlvement. Hydrcephalus and macrcephaly may be new manifestatins f NLE.2 Infants brn t mthers with anti-R antibdies shuld prbably be mnitred fr hydrcephalus as part f their rutine physical examinatin. In a nenate with cngenital heart blck r thrmbcytpenia, serum autantibdies shuld be investigated t rule ut NLE, even if a suggestive maternal histry is lacking.3 Physical Cutaneus findings A well-demarcated erythematus, mild, scaling plaque that is ften annular and appears predminately n the scalp, neck, r face is present. This plaque is typically perirbital in distributin. Similar plaques may appear n the trunk r extremities. They are smetimes crusted; this finding is bserved mre ften in male babies than in female babies. Fllicular plugging is usually nt evident. Healing tends t ccur within a year, with mild cutaneus atrphy, with r withut assciated telangiectasia. The atrphic telangiectatic changes are mst evident near the temples and scalp. The latter site may be assciated with a permanent alpecia. At times, small angimalike papulndules may be seen. Cardiac findings Mthers with primary SS r UAS have a greater risk f delivering an infant with cngenital cmplete heart blck than thse with SLE. ther disturbances may als be present. These disturbances lead t blcks in the atriventricular r Purkinje systems, such as sinus bradycardia and prlngatin f the QT interval. An irregular heartbeat may als be present. In sme cases, mycarditis and pericarditis can develp and lead t bradycardia. Hematlgic findings Autantibdies, mainly anti-R, can bind directly t the neutrphil and cause neutrpenia. These findings may imprve r disappear as maternal antibdies are metablized. Hepatmegaly 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.
Diagnosis
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.