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Neonatal lupus erythematosus (NLE) is an inflammatory disorder of neonates characterized by transient cutaneous lesions and/or congenital heart block. The cutaneous lesions usually heal with minimal scarring, but healing may be delayed for many months in occasional cases. Photosensitivity is recognized as a component of this syndrome. A large proportion of this maternal population is asymptomatic, although the mothers' potential risk for developing CTD in the future remains to be determined. Moreover, this maternal group may exhibit a tendency to fetal wastage. La(SSB) and/or Ro(SSA) antibody is almost universally present in the sera of the neonatal lupus mothers and their infants. Since these antibodies may have a pathogenetic role in NLE, screening of infants with isolated CHB and/or cutaneous lesions suggestive of LE, and their mothers, for the presence of Ro(SSA) and La(SSB) antibodies is strongly recommended. HLA studies reveal that infants of Ro-positive mothers bearing the HLA, A1, B8, DR3, MB2 and MT2 phenotypes are at increased risk of developing neonatal lupus, in sharp contrast to infants of Ro-positive mothers bearing the DR2 and/or MB1/MT1 phenotypes. Recognition of the protean manifestations of this complex disorder by obstetricians, pediatricians, cardiologists, and dermatologists will undoubtedly lead to increased detection of NLE and afford further opportunity to elucidate more fully the etiology of this syndrome.