Transient autoimmunity related to maternal autoantibodies: neonatal lupus
Introduction
Neonatal lupus erythematosus (NLE) is an uncommon autoimmune disease occurring in a small subset of infants whose mothers have anti-Ro autoantibodies. These autoantibodies cross the placenta and are presumably pathogenic. The major clinical findings are cutaneous, cardiac, hepatobiliary, and hematologic, although in a given baby it is frequently the case that only one organ is affected (Table 1).
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Cutaneous manifestations of NLE
The first discovered manifestation of NLE was cutaneous disease, and it is the cutaneous disease that gives NLE its name [1]. Most of the other clinical manifestations of NLE are arguably not truly lupus, as similar clinical findings are not characteristically observed in patients with systemic lupus erythematosus, but the cutaneous lesions grossly and microscopically are cutaneous lupus (Fig. 1).
The usual time of onset of cutaneous disease is a few days or weeks after birth, although in some
Cardiac manifestations of NLE
NLE is the most common cause of isolated congenital complete heart block, which usually has its onset during the second or third trimester of pregnancy [7]. The initial finding may be first-, second-, or third-degree heart block, but ultimately almost all cases of heart block progress to third-degree block. Once complete heart block is established, it is permanent. Autopsy studies have shown the atrioventricular nodal area to be replaced by scar tissue, explaining the irreversible nature of the
Hepatobiliary NLE
In perhaps 10% of cases, hepatobiliary involvement has been present in babies with other findings of NLE [12]. Three major phenotypes have been reported: (1) fulminant liver failure presenting at or shortly after birth, (2) cholestasis with direct hyperbilirubinemia but minimal transaminase elevations occurring as a transient, but sometimes rather dramatic, phenomenon at a few weeks after birth, and (3) otherwise unexplained transient mild to moderate transaminase elevations occurring a few
Hematologic NLE
Thrombocytopenia has been noted in about 10% of children with other manifestations of NLE, but probably occurs very infrequently as the sole manifestation of NLE [14]. Although thrombocytopenia is usually clinically silent, in one case there was gastrointestinal bleeding attributed to the low platelet count.
There are a few reports of neutropenia, notably a finding of neutropenia in 5 of 57 cases of cutaneous NLE in the NLE Research Registry/US [4]. Anemia has been reported, as has a case of
Autoantibodies of NLE
A discussion of NLE-associated autoantibodies is relevant both for diagnosis and pathogenesis. Diagnosis is usually established by a compatible clinical picture together with the presence of NLE-associated autoantibodies in maternal or infant serum. When sera are examined carefully, almost all contain antibodies the Ro, or SSA, 60-kDa protein [15]. Autoantibodies to 60-kDa Ro frequently coexist with autoantibodies to La (also called SSB) and, especially, with autoantibodies to 52 kDa Ro [16].
Therapy
Interventions may be directed at treatment of existing disease or at prevention. For treatment of cutaneous NLE, low-potency topical corticosteroids and sun protection have been the mainstays of therapy. Persistent telangiectasia may be treated with a vascular laser.
For treatment of cardiac NLE, pacemaker implantation is frequently necessary. If heart failure is present, standard medical management is often combined with systemic corticosteroids. In one case, these therapies were supplemented
Prognosis
Children who had NLE may be expected to have at least a modest increased risk to develop autoimmunity later in life, if for no other reason than they have a family history of autoimmunity (mothers with autoantibodies). The magnitude of the risk is not yet known. In a report from the NLE Research Registry/US, 49 children who had NLE and their 45 unaffected siblings, all over the age of 8, were tested for autoantibodies and queried regarding development of autoimmune symptoms or disease [26].
Pathogenesis
The fixed association of NLE with maternal autoantibodies of particular specificities and the waning of disease activity as maternal autoantibodies are metabolized are strong indicators that autoantibodies are culpable. Formally proving this assumption has not been simple, but the weight of the evidence implicates autoantibodies as an essential component in the genesis of disease.
Perhaps the most straightforward way of demonstrating the importance of autoantibodies is to reproduce the disease
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