3 | DISCUSSION
NLE is an unusual and acquired
immune-mediated disease, attributed to the presence of maternal IgG
antibodies against Ro/SSA, La/SSB, or U-RNP in the neonate. It occurs in
approximately 1 per 20,000
newborns,1 and 2%
in offspring of mothers with Sjögren’s
syndrome with an 18 to 20 percent
recurrence rate in subsequent pregnancies.2
The clinical manifestations of NLE
include annular skin rash,
cytopenia, hepatitis, and congenital heart block. Long-term follow-up is
vital in these patients, since they are at an increased risk of
developing autoimmune diseases in
late childhood or adulthood.3 Typical cutaneous
manifestations include erythematous annular plaques. In the periorbital
area, lesions frequently give rise to the typical “eye mask” or
“raccoon-like” appearance. In our case, the
skin lesions of patient 1
showed
typical annular plaques and patient
2 showed untypical rare red papules, which has not been reported so far.
The diagnosis of NLE can be confirmed through history, physical
examination and the presence of specific antibodies in fetal and
maternal circulation. Skin biopsy is useful, although not essential to
establish diagnosis. Differential diagnosis includes congenital
syphilis, tinea corporis, sarcoidosis, granuloma annulare, Langerhans
histiocytosis, Sweet syndrome and urticaria.
Although cases of NLE among siblings
have been reported,4 they all have the same or similar
manifestations, and it is very rare, because of the high risk of
pregnancy in affected women.
In
our case, it is the first description of
cutaneous NLE to occur in two
siblings with significantly
different cutaneous manifestations. Various clinical expressions may be
explained by a different specificity of Anti-Ro autoantibodies among
siblings.5 Some
authors have suggested that apart from maternal immunoglobulin G
antibodies, other foeto-maternal
factors including environmental,
intrauterine or genetic influences may affect the pathogenesis and
expression of NLE.6
Pregnant women who test positive for autoantibodies to Sjögren’s
syndrome autoantigens types A or B are thought to have a risk pregnancy,
above all those with a previous
history of NLE,7 because the risk of NLE in children
of future pregnancies is increased.2 In our case,
although the mother’s Sjogren’s syndrome was not well controlled, she
still insisted on having a second child. Therefore, we should strengthen
the management of the mother, and it is recommended to get pregnant
after the condition is controlled, so as to reduce the recurrence rate
of NLE.
The management includes counseling
advice, fetal screening, maternal screening, and prevention or
management of the heart disease.7Current
recommendations are to monitor
the fetal PR interval by
echocardiogram weekly between 16 and 26 weeks’ gestation, and biweekly
between 26 and 32 weeks. In our
case, it was very dangerous for the mother and her fetus not to monitor
the fetal PR interval by
echocardiogram during pregnancy.
Avoidance of sun exposure including
sunscreen and protective clothing is the mainstay of management for
infants with cutaneous
manifestations,8 just like in our case, both children
only presented with rashes, the key
of the management is photoprotection. The rash
of patient 1
progressively disappeared over a
period of 6 months, and did not recur or developing autoimmune diseases
during the 7-year follow-up. The
rash of patient 2 start to
partially subside from two and a
half months. At present, he is still in follow-up, and is ordered to
return to the hospital every month to
monitor biochemical
tests、echocardiogram and ECG.
Global fertility declines have become an inevitable trend. As a result,
many countries are adopting policies to drive fertility increases. For
example, Chinese government began to
fully liberalize the two-child policy
in 2016,9 and it further fully liberalized the
“three-child” policy in 2021. The
two-child policy won’t result in a baby boom, but rather a moderate
increase in
fertility,10 and
it has
led
to more families having a second child.11 Therefore,
it is estimated that the incidence rate of NLE
in siblings
will
increase too, so we should raise the
awareness of NLE in siblings, which is very important for the
monitoring, evaluation, diagnosis and management of NLE.
Author Contributions:
Pengyue Tang: Have made substantial contributions to conception
and design, or acquisition of data, or analysis and interpretation of
data. Drafted the manuscript.
Ping Li: Revised the manuscript critically for important
intellectual content. Given final approval of the version to be
published.