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.