Neonatal lupus erythematosus

 

Neonatal lupus erythematosus (NLE) is a well‐recognized subtype of lupus erythematosus, thought to be caused by the transplacental passage of auto- antibodies from the mother to the fetus. This syndrome is characterized by one or more of the following findings: subacute cutaneous lupus–like annular and polycyclic lesions, congenital heart block, cardiomyopathy, cholestatic hepatitis, and thrombocytopenia.

 

Epidemiology

 

Incidence and prevalence

 

Congenital heart block occurs in 1–2% of children born to mothers positive for the Ro antibody, whilst neonatal lupus occurs in 8–10% of these mothers.

 

Associated diseases

 

The condition occurs in the offspring of women with positive Ro/SSA antibodies and occasionally La/SSB antibodies. The mothers may not have clinical evidence of lupus or Sjogren syndrome.

 

Pathophysiology

 

NLE is caused by the transplacental passage of maternal IgG anti–Ro/SS-A and/or anti–La/SS-B or anti-U1RNP. Most babies of mothers with anti–Ro/SS-A, anti–La/SS-B, or anti-U1RNP autoantibodies do not develop NLE. There is no way to determine which fetus or infant will be affected. The presence of the Ro/SSA antibody is strongly associated with NLE, being present in 100% of both infants and mothers. Two main Ro/SSA antibody exist (52 and 60KDa) and studies have suggested that the former is more frequently found in CHB while the later 60 kDa  is more frequently associated with cutaneous disease. 

 

 

 

 

 

 

Clinical features

 

Many cases present with either skin or heart problems with no preceding disease in the mother.

 

Cutaneous features

 

The skin lesions (present in approximately 50% of affected infants) which may be present at birth or appear within the first month of life. Subacute cutaneous lupus like lesions (annular erythematous scaling plaques) are present on the scalp, periocular region (raccoon eyes/“owl-eye” or “eye mask”), and malar area. Lesions may also appear on the arms and legs, trunk, and groin. Crusted lesions predominate in male infants. Photosensitivity is very common in NLE as the eruption can be exacerbated by UV exposure but sun exposure is not required for lesions to form, as it is possible for lesions to be present at birth. There are reports of the rash being precipitated by phototherapy for neonatal jaundice. Skin lesions resolve by 6 months of age as auto antibodies wane but may leave dyspigmentation and telangiectasias.

Infants who have the cutaneous lesions of NLE may also exhibit internal manifestations. The major extra cutaneous findings are congenital heart block (with or without cardiomyopathy), hepatobiliary disease and cytopenias, in particular thrombocytopenia.

 

 

Cardiac features

 

The congenital heart block (present in approximately 50% of affected infants) is a permanent defect that develops in utero during the late second and the third trimesters of pregnancy. The heart block is almost always present by birth, but on rare occasions has developed after birth. Clinically significant cardiomyopathy occurs concurrently in a small percentage of babies who have heart block. Usually, the cardiomyopathy is apparent during the neonatal period, but it is possible for it to become apparent only after several months have elapsed. Approximately two-thirds of babies require pacemakers, and approximately 10% die of complications related to cardiac disease. The proposed cause is that the anti–Ro/SS-A antibody binds with an auto antigen in the heart and produces an inflammatory process, resulting in fibrotic replacement and destruction of one or more of the following: the sinoatrial bundle, the atrioventricular bundle, or the bundle of His.

 

 

Other features

 

Hepatobiliary disease and cytopenias, especially thrombocytopenia, may be present at birth, or they may develop within the first few months of life. Hepatobiliary disease can vary in severity and may present as liver failure during gestation or in the neonatal period, conjugated hyperbilirubinemia during the first few weeks of life, or mild elevations of aminotransferases at 2–3 months of life. There are also reports of hydrocephalus, microangiopathic hemolysis, and disseminated intravascular coagulation.

 

Disease course and prognosis

 

The rash improves over the first few months of life and has usually resolved without scarring by 12 months of age as auto antibodies wane. Occasional patients exhibit residual telangiectasia, dyspigmentation or atrophy. The heart block is permanent and usually requires a permanent pacemaker.

 

Infant

 

Some children have gone on to develop autoimmune disease, even in childhood. Follow‐up is therefore advised.

 

Mother

 

Although mothers are often asymptomatic at the time of the birth, long‐term follow‐up studies have shown that many develop signs and symptoms of autoimmune disease, especially Sjögren syndrome, SLE and undifferentiated connective tissue disease. Follow‐up is therefore advised.

 

 

Investigations

 

Antibody testing is required in both child and mother. Cardiac investigation is also required to assess cardiac status, and in an at‐risk pregnancy screening with cardiac ultrasound should begin during the pregnancy.

 

Although most children with cutaneous NLE do not have significant internal involvement, a systemic evaluation and counseling is recommended.

 

 

Systemic evaluation of an infant with cutaneous neonatal lupus erythematosus(NLE)

In the setting of characteristic skin lesions, the diagnosis is established via autoantibody testing in the mother (anti-SSA/Ro autoantibodies) +/− in the infant (anti-SSA/Ro, -RNP); if skin lesions are atypical, histologic examination may be required. AI-CTD, autoimmune connective tissue disease; CBC, complete blood count.

 

SYSTEMIC EVALUATION OF AN INFANT WITH CUTANEOUS NEONATAL LUPUS ERYTHEMATOSUS

Initial and serial evaluations until 6–9 months of age

1.   History, review of systems & physical examination: examination includes monitoring of growth and head circumference*; frequency depends upon degree of systemic involvement 2.   Laboratory studies: electrocardiogram +/− echocardiogram, CBC with differential and platelet count, liver function tests; if tests are initially normal and infant without signs or symptoms, then tests repeated every 2–3 months × 2–3 (otherwise more frequently) 3.   Family counseling and care coordination: risk for NLE in subsequent pregnancies, risk for development of AI-CTD in mother and, possibly, child 4.   Preemptive treatment: for mothers of infants with cardiac NLE, consider hydroxychloroquine during subsequent pregnancies

Long-term considerations

1.   History and physical examination: periodically per pediatrician 2.   Laboratory studies: if normal or return to normal and the child remains healthy, further testing is not required 3.   Risk of AI-CTD as adolescent/adult

 

 

 

Treatment

 

Recognition of the condition in a neonate is important for this and subsequent children and of at‐risk pregnancies should always be monitored.

 

Cutaneous lesions

 

Skin disease is often mild and often requires no treatment. Sun avoidance should be advised and low‐potency topical steroids may be of benefit. Antimalarials may be necessary for persistent skin disease. Persistent telangiectasia has been reported to respond to the tunable dye laser.

 

 

Cardiac problems

 

Up to 50% may require pacing in the newborn period, and others may require pacemaker insertion at a later date. Whether CHB and its consequences can be prevented or treated in utero. Oral steroids (dexamethasone/betamethasone 4mg/day) or hydroxychloroquine given to the mother in the first 16 weeks of pregnancy may influence both cutaneous and cardiac pathology, and prevent conduction defects. Later administration is not beneficial in reversing established CHB.

 

 

Haematological and hepatic problems

 

Most resolve spontaneously without treatment.

 

 

Pregnancy

 

A pregnant patient who is known to have Ro/SS‐A or La/SS‐B antibodies and her obstetrician should be made aware of the possible problems. The risk of NLE is 10 folds in subsequent pregnancies. Serial fetal echocardiography is recommended and performed by an experienced pediatric cardiologist in case of suspected fetal dysrhythmia or myocarditis, especially in mothers with a positive anti Ro/SS‐A and La/SS‐B antibodies.Ro/SS‐A and La/SS‐B antibodies in human breast milk have no pathological consequences.