Objectives: Neonatal lupus erythematosus (NLE) is associated with maternal anti-Ro/La autoantibodies. It is characterized by heart block and/or cutaneous skin lesions, and occasionally liver disease. This study was performed to determine whether idiopathic neonatal cholestasis (INC) represents NLE without its cardiac or cutaneous findings.
Methods: Sera were obtained for autoantibody analysis from mothers of children with INC (N = 11), biliary atresia (N = 25), other liver disease excluding viral hepatitis (liver disease control subjects, N = 14), and healthy children (normal control subjects [NC], N = 22).
Results: The characteristic serologic findings of NLE, high titer antibodies to Ro and/or La, were absent in mothers from all groups. An unexpected finding was the prevalence of autoantibodies in mothers of infants with liver disease of any type. The frequency of maternal antinuclear antibodies at ≥ 1:120 dilution was greater than the estimated frequency in the general population (22% vs. 9%, P = 0.044). The frequency of maternal low titer autoantibodies to 52 kD Ro detected by ELISA was significantly greater than in the NC group (31% vs. 5%, P = 0.014).
Conclusions: The majority of cases of INC do not represent NLE. The frequent presence of autoantibodies in mothers of infants in all neonatal liver disease groups raises the possibility that maternal serologic autoimmunity is associated with neonatal liver disease.
ABBREVIATIONS: NLE = neonatal lupus erythematosus, INC = idiopathic neonatal cholestasis, BA = biliary atresia, LDC = liver disease control group, NC = normal control group, SLE = systemic lupus erythematosus, ANA = antinuclear antibodies, OD = optical density
Neonatal lupus erythematosus (NLE) is an autoimmune disease that has the principal clinical manifestations of congenital heart block and cutaneous lupus lesions (1,2). Virtually all infants with NLE have transplacentally transferred maternal IgG autoantibodies to Ro (SSA) and many to La (SSB). Accumulating evidence indicates that these autoantibodies cause the disease (3). Although cardiac and cutaneous findings are the major manifestations of NLE, they do not usually occur concurrently in the same patient. Most infants with NLE present with only one organ system involved (1). NLE is a relatively rare disease, occurring in approximately 1 in 20,000 live births.
There are several case reports of infants with cardiac or cutaneous NLE who also have hepatobiliary disease (4–10). The initial case reports of liver disease in NLE described a characteristic transient cholestasis, clinically similar to idiopathic neonatal cholestasis. A recent review of the database of a national registry of NLE cases suggests that NLE liver disease may have other phenotypes as well. Several patients with NLE experienced liver failure, with the histologic appearance of neonatal iron storage disease or “neonatal hemochromatosis.” Some had only transient mild aminotransferase elevations (11). Hepatobiliary disease probably or possibly caused by NLE was not rare in the registry group, being noted in almost 10% of cases.
There are only four case reports of hepatobiliary disease possibly attributable to NLE occurring in the absence of cardiac or cutaneous disease (11–13), and in all four cases there was liver failure. To our knowledge, there have been no cases of transient cholestatic disease attributed to NLE occurring in the absence of other manifestations of NLE. Because cardiac and cutaneous diseases commonly occur in the absence of other clinical findings, we questioned whether hepatobiliary disease could also occur as an isolated clinical manifestation of NLE. Thus, the major hypothesis to be tested was that some cases of idiopathic neonatal cholestatic hepatobiliary disease represent NLE. Because NLE is invariably associated with maternal autoantibodies, and NLE-associated autoantibodies tend to persist rather than wax and wane in maternal sera (14), our study design focused on autoantibody testing of maternal sera. We compared sera from mothers of infants with neonatal cholestatic conditions to that of mothers of healthy infants.