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Abstract

  1. Top of page
  2. Abstract
  3. Cutaneous Neonatal Lupus Erythematosus (CNLE)
  4. Liver disease
  5. Haematological NLE
  6. Neurologic
  7. Chondrodysplasia punctata
  8. References

Neonatal lupus erythematosus (NLE) is characterized by the transplacental passage of maternal anti-Ro and/or anti-La antibodies and characteristic illnesses in the foetus/neonate. Most attention has focused on the most serious complication- cardiac involvement. This article will focus on non-cardiac involvement. Skin involvement (cutaneous NLE) is present in 15–25% of children with NLE. The rash of NLE tends to be photosensitive but may be present at birth or in non-sun exposed areas. It is most frequently seen around the eyes, not in the malar area, but also occurs in other parts of the body. The pathology resembles the rash of subacute cutaneous lupus erythematosus. Anti-Ro antibodies are present in >95% with the remaining mothers having anti-U1RNP antibodies only. Asymptomatic elevation of liver function tests, which may be associated with evidence of cholestasis, is seen in 10–25% of cases of NLE. Mild hepatomegaly and less commonly splenomegaly may be present. Liver involvement seen in isolation or associated with other features. The pathology resembles idiopathic neonatal giant cell hepatitis. Any haematological lineage, neutropenia and thrombocytopenia most commonly, may be affected by NLE. Haematological involvement is almost always asymptomatic. There are protean manifestations of neurologic involvement in NLE: hydrocephalus, non-specific white matter changes, calcification of the basal ganglia and a ‘vasculopathy’. The most unusual feature of NLE is the radiographic finding of stippling of the epiphyses (chondrodysplasia punctata). Overall, non-cardiac involvement of NLE is more common than cardiac. The study of these manifestations may lead to new insight into how autoantibodies lead to disease.


Cutaneous Neonatal Lupus Erythematosus (CNLE)

  1. Top of page
  2. Abstract
  3. Cutaneous Neonatal Lupus Erythematosus (CNLE)
  4. Liver disease
  5. Haematological NLE
  6. Neurologic
  7. Chondrodysplasia punctata
  8. References

Although the first case of a skin in a neonate of a mother with an autoimmune disease was first reported in 1954 [1], the association of cutaneous disease in these infants with maternal anti-Ro antibodies was not until 1979 [2]. Unlike congenital heart block, which is relatively easy to diagnosis, the rash of Neonatal lupus erythematosus (NLE) may be subtle and mistaken for another neonatal rash particularly in infants born to mothers who are clinically well. Therefore, although the rash of NLE is reported to be present in 15–25% of children with NLE, the true percentage of children with cutaneous NLE is difficult to accurately determine [3]. It had initially been reported that there was an increased incidence of rash in female neonates when compared to males, with a female-to-male ratio of 2:1 to 3:1 [4, 5]. This observation resulted in the hypothesis that the increased incidence in females was related to the observation that estrogens enhance surface expression of Ro and La proteins on keratinocyte cells [6]. However, the large US national Neonatal Lupus registry (RRNL) did not confirm the suggested female predominance, as only 55% of 139 infants with rash were female [7].

The rash of NLE tends to be photosensitive but this is not mandatory as the rash may be present at birth or in non-sun exposed areas such as plantar surface of the feet or palms of the hands and in the diaper area. The dermatitis tends to resemble the rash of subacute cutaneous lupus erythematosus (SCLE) or annular erythema and not the malar rash of systemic lupus erythematosus. It is most frequently seen around the eyes and not in the malar area, it can occur in area part of the body including the diaper area. Although usually maculopapular with a scale, bullous lesions may be seen with a particular predilection for the soles of the feet. The most common time for the rash to be detected is between 4 and 6 weeks of age but may be present at birth. The mean duration of the rash is 15–17 weeks [8].

Pathology

The pathology of the rash tends to resemble the rash of SCLE, and it has been divided into erythematous-desquamative and urticaria-like lesions [9].

Autoantibodies

Greater than 95% of mothers have circulating anti-Ro antibodies although there have been cases of anti-Ro and anti-La antibody negative but anti-U1RNP-positive mothers [10, 11]. The percentage of mothers of children with CNLE with anti-La antibodies is higher than the percentage of mothers of children with congenital heart block and these autoantibodies and the titres tend to be higher [12].

Treatment

The rash usually heals without treatment although the judicious of corticosteroids may hasten its resolution. There is no evidence that treatment of the rash prevents scars or telangectasiae that develop in approximately 10–20% of children [8].

Liver disease

  1. Top of page
  2. Abstract
  3. Cutaneous Neonatal Lupus Erythematosus (CNLE)
  4. Liver disease
  5. Haematological NLE
  6. Neurologic
  7. Chondrodysplasia punctata
  8. References

Liver involvement with NLE usually presents with asymptomatic elevated liver function tests (usually alanine aminotransferase and/or aspartate aminotransferase) which may be associated with evidence of cholestasis [13, 14]. These infants may have mild hepatomegaly and less commonly splenomegaly. Similar to other features, liver involvement may be the only manifestation of maternal anti-Ro or anti-La antibodies. The LFT elevations are usually transient and generally resolve within the first months of post-natal life without sequelae. Therefore, we suggest that the reported occurrence rate of 15% [15] is an underestimate and that it is likely closer to the 25% rate we reported in a prospective study [16].

The pathology of liver involvement tends to resemble idiopathic neonatal giant cell hepatitis although more severe lesions associated with death have been described [13, 17, 18].

Haematological NLE

  1. Top of page
  2. Abstract
  3. Cutaneous Neonatal Lupus Erythematosus (CNLE)
  4. Liver disease
  5. Haematological NLE
  6. Neurologic
  7. Chondrodysplasia punctata
  8. References

Although the transplacental passage of maternal autoantibodies can effect any haematological lineage, it had been suggested that platelets were the most common lineage involved [19]. It appears that this may be the most common manifestation within the first week of life and in our experience tends to resolve by 2–4 weeks of age. When we routinely measured blood counts at 4–8 weeks, we found that neutropenia was much more commonly seen than thrombocytopenia occurring in up to 10–15% of children born to mothers with anti-Ro antibodies [16]. Similar to the infants with thrombocytopenia who rarely have bleeding problems, children with neutropenia do not have problems with infection. More rarely, a haemolytic anaemia or even a pancytopenia or aplastic anaemia has been reported secondary to NLE [20, 21].

Neurologic

  1. Top of page
  2. Abstract
  3. Cutaneous Neonatal Lupus Erythematosus (CNLE)
  4. Liver disease
  5. Haematological NLE
  6. Neurologic
  7. Chondrodysplasia punctata
  8. References

We have had a great interest in neurologic involvement in NLE after observing a child with a CNLE develop hydrocephalus. However, our observation had been preceded by a report by Nakayama-Furukawa who described two cases of hydrocephalus secondary to NLE in 1994 [22]. We then prospectively examined 87 infants and found that 8% of infants born to mothers with anti-Ro antibodies had hydrocephalus. The highest incidence of macrocephaly was detected between 12 and 24 months of age [23].

A combined CT scan and ultrasound study of 11 consecutive infants with CNLE showed mild ultrasound and/or abnormalities 9. The most frequent CT findings were as follows: non-specific white matter changes, calcification of the basal ganglia, and macrocephaly, a ‘vasculopathy’, and a case of transient myasthenia gravis associated with maternal anti-Ro and anti-La antibodies [24–27].

Chondrodysplasia punctata

  1. Top of page
  2. Abstract
  3. Cutaneous Neonatal Lupus Erythematosus (CNLE)
  4. Liver disease
  5. Haematological NLE
  6. Neurologic
  7. Chondrodysplasia punctata
  8. References

Chondrodysplasia punctata is a rare condition characterized by radiographic evidence stippling of the epiphyses and/or the spine. It generally resolves without treatment during childhood within the first year. There are multiple aetiologies that include genetic disorders, foetal viral exposure and the use maternal medications including dilantin, warfarin and maternal vitamin K deficiency [28]. The first reports of the association of chondrodysplasia punctata with NLE appeared in 1993 by our group and from Reichlin group in Oklahoma were presented on bone dysplasia meetings [28]. One case was associated with intra-uterine death and bone histology in this case showed evidence of small foci of dystrophic calcification with otherwise normal ossification [29]. Including the initial reports, there have been more than 15 cases of Chondrodysplasia punctata associated with maternal autoantibodies [28–34], and it is therefore likely that this is a skeletal manifestation of NLE.

References

  1. Top of page
  2. Abstract
  3. Cutaneous Neonatal Lupus Erythematosus (CNLE)
  4. Liver disease
  5. Haematological NLE
  6. Neurologic
  7. Chondrodysplasia punctata
  8. References