Discussion
Neonatal lupus erythematosus (NLE) is an uncommon condition associated with maternal anti-Ro and anti-La autoantibodies. These autoantibodies are passively transferred to the foetus through the placenta, and once in the foetal circulation promote the development of NLE by binding to antigen. Anti-Ro and anti-La autoantibodies bind to nuclear antigens translocated to the cell membranes of apoptotic cells, in particular myocardiocytes and keratinocytes. Macrophages expressing Fc receptors recognise bound IgG and become activated and initiate inflammatory responses. This antigen binding is found to cause cutaneous lupus lesions, third-degree heart block, cardiomyopathy, hepatobiliary disease, and thrombocytopenia or other haematologic cytopenias. In this case study we see cutaneous and hepatic involvement accompanied by a pancytopaenia. Studies have found that anti La antibodies are associated with cutaneous lupus and anti Ro antibodies are associated with congenital heart block. Anti-platelet antibodies are present which cause destruction of platelets while anaemia is caused by both antibodies and haemorrhage. In this case haemorrhage is evidenced by haematochezia, haematuria and intracranial bleeds. Pancytopaenia is also further exacerbated by hypersplenism which can result in patients undergoing splenectomy if the condition is not resolved. Typically only one organ is affected in NLE, but any combination of organ involvement may occur. Pregnant women with anti-Ro and anti-La antibodies have a 5-20% risk of having a child/children with NLE, with the risk being highest in mother’s with high titre antibodies.
Although during pregnancy, maternal IgG autoantibodies are transported to the foetus via the placenta after birth the foetal levels of Ro and La IgG autoantibodies are found to rapidly decrease suggesting that after placental detachment the source of immunoglobulins is markedly decreased or ended. Although breast milk also contains IgA and IgG autoantibodies the dose or foetal uptake is not enough to reach detectable levels.
The most common severe manifestation of neonatal lupus is third-degree heart block, which usually begins during the second trimester of gestation and once established is irreversible. This is thought to occur from the inflammatory process that results from the macrophages expressing Fc receptors which recognise the bound IgG. The secretion of pro-inflammatory cytokines causes inflammation and ultimately fibrosis in the cardiac tissue. These patients require the insertion of a pacemaker to maximize heart function. If cardiomyopathy is also present this can be fatal.
Otherwise for the most part NLE is transient. The cutaneous lesions are what give the neonatal “lupus” its name, as the lesions are clinically and histologically consistent with cutaneous lupus having the major features of keratinocyte damage and mononuclear cell infiltrate. Skin lesions often present at a few weeks of life, but may be present at birth. Spontaneous resolution within weeks or months without permanent residua is the expected outcome. Affected individuals tend to be healthy later in childhood. There does however appear to be an increased risk for children who have had NLE to develop autoimmune diseases later in childhood or adulthood such as juvenile rheumatoid arthritis, Hashimoto thyroiditis and diabetes mellitus.
At present, practices and opinions differ regarding recommendations for prophylactically treating anti-Ro positive women during pregnancy. What is generally agreed on is that if systemic corticosteroids are given, dexamethasone or betamethasone are better choices than prednisone or prednisolone, as they are not inactivated by placental enzymes and so reach the fetal circulation largely intact.
It is quite often the case that autoimmunity in the mother is not detected until the birth of her first child with NLE. Several studies indicate that, with time, the mothers who were initially asymptomatic eventually develop signs and symptoms of autoimmunity themselves, in particular Sjögren syndrome, systemic lupus erythematosus and undifferentiated connective tissue disease.
