Background Congenital atrioventricular block (CHB) is the most frequent manifestation of neonatal lupus and depends on anti-Ro/SSA and/or anti-La/SSB-mediated inflammation and subsequent fibrosis of the atrioventricular node. No therapy has yet been found to be effective in treatment of second and third degree CHB induced by maternal autoantibodies, and due to the rarity of the disease controlled clinical trials and not possible to perform.
Objectives To evaluate the clinical efficacy and safety of a combined therapy protocol utilizing plasmapheresis, intravenous immunoglobulin (IVIG) and betamethasone, and the effect of this treatment on anti-Ro52, anti-p200 and anti-La antibody levels.
Methods Six consecutive women pregnant with fetuses diagnosed CHB (3 with 2nd degree and 3 with third degree CHB) underwent a combination therapy protocol composed of weekly plasmapheresis, fortnightly 1 g/Kg IVIG and daily 4 mg Betamethasone throughout pregnancy. IVIG (1 g/Kg) treatment in the neonates was begun at birth and administered every fifteen days until maternal autoantibodies became undetectable by ELISA in the circulation of the neonates. The anti-Ro52, anti-p200 and anti-La antibody levels were investigated by ELISA in serial sera of 4 mothers obtained before and after each plasmapheresis.
Results The foetuses affected with second degree block (case 1, 2 and 3) reverted to a normal atrio-ventricular conduction during pregnancy, while those with a third degree block remained stable (case 4), showed a higher ventricular rate (case 5), or an improvement in cardiac function (case 6). These results improved the chances for survival and delayed the need for a pacemaker. No severe cardiac complications such as impaired ventricular function, hydrops or cardiomyopathy were observed in the foetuses with third degree CHB. We found that plasmapheresis significantly decreases the anti-Ro52, anti-p200 and anti-La antibody levels in all cases, except anti-Ro52 antibodies in the two patients with the highest autoantibody titers. Indeed, analysis by linear regression demonstrated that patients with high autoantibody levels had lesser decrease in anti-Ro52 antibody levels.
Conclusions Overall, lessons learned from these case series are: A) an efficacy in treating second degree CHB, and b) the safety of plasmapheresis and IVIG therapies. The low number of treated cases, the relatively short follow-up (mean 22.7 months ± 10.4, range 12-42 months) and the high cost of the procedure can all be considered limits. Weekly plasmapheresis reduces the levels of anti-Ro52, anti-p200 and anti-La antibodies in patients with medium-high autoantibody titers. However, there is a limited effect on autoantibody levels in patients with very high autoantibody titers.
Disclosure of Interest None Declared