新生儿红斑狼疮5例分析

目的探讨新生儿红斑狼疮(NLE)的诊断和治疗方法。方法对5例NLE患儿的临床表现及实验室检查进行分析,并复习相关文献。结果患儿皮损类似SCLE,局限或全身分布,以颜面、躯干及四肢末端为重,患儿及其母亲ANA、抗Ro/SSA及/或抗La/SSBIgG抗体均阳性,心电图检查未见心脏传导阻滞,未经治疗数周后自然消退。结论根据皮损表现和实验室检查可诊断新生儿红斑狼疮,一般不需治疗。     

Immune responses to SS-A 52-kDa and 60-kDa proteins and to SS-B 50-kDa protein in mothers of infants with neonatal lupus erythematosus

Mothers who have anti-SS-A/Ro and anti-SS-B/La antibodies have a greater risk of bearing infants with neonatal lupus erythematosus (NLE). However, most mothers with anti-SS-A/Ro and anti-SS-B/La antibodies give birth to infants with no evidence of NLE. We studied mothers who had the combination of clinical evidence of connective tissue disorder, positive antinuclear antibody and positive anti-SS-A/Ro and/or anti-SS-B/La antibodies. We analysed SS-A/Ro and SS-B/La antibody responses to recombinant 60-, 52- and 50-kDa proteins in eight mothers of NLE infants and 19 mothers whose children did not have NLE. Molecular analysis of the anti-SS-A/Ro and anti-SS-B/La antibodies was carried out by enzyme-linked immunosorbent assay using recombinant 60-, 52- and 50-kDa proteins. The mothers of children with cutaneous NLE were all positive for a high titre of 50-kDa protein. Mothers of children with NLE with complete heart block (CHB) were positive for 52- and 60-kDa proteins. We conjecture that anti-SS-B/La antibody influences the development of cutaneous NLE, and that anti-SS-A/Ro antibody influences the development of NLE with CHB.     

Significance of tubuloreticular structures forming in Daudi cells cultured with sera from mothers bearing infants with neonatal lupus erythematosus

It is known that infants with neonatal lupus erythematosus (NLE) may be born to mothers whose sera are positive for the anti-Ro/SSA antibody. However, women who have this antibody do not always give birth to children with NLE. We have demonstrated tubuloreticular structures in vascular endothelial cells in the skin lesions of infants with NLE. Tubuloreticular structures could no longer be detected at the site of the lesions once the annular erythema had resolved, and the anti-Ro/SSA antibody test had become negative. The probability of a child being born with NLE was assessed by observing whether tubuloreticular structures were formed in Daudi cells cultured with sera from eight mothers who were anti-Ro/SSA antibody positive. Tubuloreticular structures formed in Daudi cells cultured with sera from four mothers who bore infants with NLE, but not in Daudi cells cultured with sera from four other mothers who bore normal infants. These results suggest that women who are positive for the anti-Ro/SSA antibody have a higher risk of bearing infants with NLE if tubuloreticular structures are formed in Daudi cells cultured with sera from these women, whereas this risk is lower if tubuloreticular structures do not develop in Daudi cells.     

Neonatal Lupus Syndrome Associated with Ribonucleoprotein Antibodies

Neonatal lupus erythematosus (NLE) is a rare acquired autoimmune disease caused by transplacental transfer of maternal immunoglobulin G antibodies to the fetus. NLE has well‐recognized cutaneous features and may also manifest in other organs. The majority of cases are associated with Ro/SSA and La/SSB antibodies. Neonatal lupus due to antiribonucleoprotein (RNP) antibodies has rarely been reported. On rare occasions RNP has been found in association with other antibodies. We report a case of NLE occurring solely due to RNP antibodies presenting as varicelliform lesions at birth. We recorded the features in our case and 14 additional cases identified in the literature. It is important to recognize that maternal transfer of RNP antibodies may produce the classic cutaneous features of neonatal lupus. The limited case reports of this condition suggest that manifestations are limited to the skin; specifically, there are no reports of cardiac involvement. The long‐term outcome remains unknown. RNP‐positive, Ro/La‐negative NLE seems to represent a different clinical subset of NLE. The recognition of RNP antibody NLE as a benign condition limited to the skin is helpful in planning antenatal care for subsequent pregnancies.     

Neonatal lupus erythematosus

We present a case of neonatal lupus erythematosus (NLE) in a black infant presenting with symmetrical depigmented macules on the face resembling vitiligo. NLE is a rare condition affecting newborn infants of mothers who have connective tissue disease, with or without autoantibodies to extractable nuclear antigens Ro (SS-A), La (SS-B) or ribonucleoproteins. Infants present with cutaneous lesions or congenital heart block or both. The skin lesions are usually annular and erythematous and transient and resemble those of subacute cutaneous lupus erythematosus. The presentation of this patient was therefore striking.     

Neonatal lupus erythematosus infants and their mothers: a 10-year retrospective study

BackgroundNeonatal lupus erythematosus (NLE) is a rare disease associated with transplacental transfer of maternal anti-Ro/anti-Sjögren syndrome A antibodies. The most common manifestations are cutaneous erythema and congenital heart block. Mothers of infants with NLE are either asymptomatic or diagnosed with autoimmune disease. The goal of this study is to investigate the clinical manifestation, prognosis, and association with autoimmune disease in NLE babies and their mothers in Taiwan.MethodsMedical records of newborns with NLE and their mothers from two hospitals in Taiwan between January 1999 and January 2009 were reviewed. Twenty-five newborns (one set of twins) and 24 mothers of infants with NLE were included in the study. Clinical data, including characteristics of skin manifestations, the onset of symptoms, and infants' antibody titers, were collected. A diagnosis of NLE was made if the baby had heart block or characteristic skin lesions and maternal antibodies to Sjögren syndrome A/Ro, Sjögren syndrome B/La, or U1 ribonucleoproteins. Questionnaires were used to determine the mother's health status at the time of delivery and in subsequent years.ResultsOf the infants, 84% had typical cutaneous manifestations of NLE, and 16% presented with congenital heart block without skin changes. The cutaneous lesions appeared on average at 21.7 weeks. Thirteen mothers were initially asymptomatic, and the other 11 remained asymptomatic over a mean follow-up period of 3.9 years. Two mothers developed lupus nephritis.ConclusionThere was a lower incidence of observed congenital heart block compared to previously reported NLE studies among Caucasian populations. Most mothers were asymptomatic before the birth of their NLE child, and few developed autoimmune diseases. However, continued follow-up of asymptomatic NLE mothers is recommended due to the chances of developing a life-threatening, systemic autoimmune disease.     

新生儿红斑狼疮与抗Ro/SSA和抗La/SSB抗体阳性2例

报告了 2例新生儿红斑狼疮。 1例出生后发现有心脏房室传导阻滞和室间隔缺损 ,脐血检测有抗Ro/SSA和抗U1RNP抗体 ,母亲为SLE患者。 1例出生后 1个月于面部、颈部及躯干上部出现环形红斑样皮疹 ,脐血检测有抗Ro/SSA和抗La/SSB抗体 ,母亲为SCLE患者。 2例患儿皮疹和心脏传导阻滞于生后 3个月内消退 ,自身抗体于生后 6个月内消退 ,随访 7年和 1 5年后均健康。     

Neonatal lupus erythematosus: factors which may lead to clinical disease in the foetus even in the absence of disease in the mother

Neonatal lupus erythematosus (NLE) occurs in neonates of mothers who, in almost all cases, have auto-antibodies to the SSA/Ro associated proteins, but who may have no clinical disease. However, only a small percentage of mothers with SSA/Ro antibodies have affected babies, predisposing factors specific to the foetus or neonate (i.e. HLA pattern) and/or fetal maternal interactions have been proposed to be important. We present a mother with a family history of autoimmune disease, but without clinical disease, whose baby developed cutaneous NLE. Autoantibody determinations as well as the HLA-DR/DQ were performed in the mother and baby. Factors other than the HLA-DR/DQ status of the mother appear to be important in determining whether or not the neonate will develop NLE. Auto-antibodies to endogenous antigens common to the mother, transiently expressed developmental antigens, and the isotype specificity of transferred antibodies may be important in determining disease in the baby.     

U1RNP positive neonatal lupus erythematosus: association with anti-La antibodies?

Summary Neonatal lupus erythematosus (NLE) is an antibody-mediated disorder most commonly associated with autoantibodies to Ro and/or La antigens. There have been five previous reports describing eight NLE patients with anti-U₁RNP antibody in the absence of anti-Ro and anti-La autoantibodies. We report two cases of anti-U₁RNP antibody-positive NLE, and briefly review the five previous reports. The diagnosis of NLE was based on physical examination and serotogical studies by ELISA, immunodiffusion, and immunoblotting. By conventional immunodiffusion and ELISA, our cases were negative for anti-Ro and anti-La antibodies, and positive for anti-U₁RNP antibody. However, one of the mothers had anti-La antibody detected by immunoblot assay only. All anti-U₁RNP antibody-positive infants had classic cutaneous lesions of NLE, but it is of interest that none had congenital heart block (CHB). Although these infants were negative for anti-Ro and anti-La antibodies with immunodiffusion and EL ISA techniques, these antibodies might be detectable by immunoblotting, as was the case in one of the mothers.     

IgG subclasses in the serum and skin in subacute cutaneous lupus erythematosus and neonatal lupus erythematosus

IgG subclasses differ in their biologic and chemical properties, such as complement fixation, protein and cellular binding, and placental transfer. In this study, IgG subclasses of anti-Ro/SSA antibodies in subacute cutaneous lupus (SCLE) and neonatal lupus (NLE) are examined in the serum and in the skin. IgG subclasses in NLE beginning in utero (NLE-heart disease) are compared to subclasses in NLE beginning after birth (NLE-skin disease). Human skin was grafted onto athymic mice, mice were injected with one of eight anti-Ro/SSA maternal NLE sera (four heart block, four skin disease) or seven anti-Ro/SSA SCLE sera, and grafts were examined for IgG subclasses using monoclonal anti-human IgG subclass reagents in an immunofluorescent technique. Lesional skin was examined from four SCLE patients. IgG1 was the only IgG subclass detected in the grafts and skin lesions. IgG1 was the predominant anti-Ro/SSA IgG subclass detected in SCLE and NLE sera in an ELISA using a synthetic Ro/SSA polypeptide. These studies show that the maternal anti-Ro/SSA autoantibodies in NLE-heart disease sera are predominantly IgG1 and are therefore likely to be present in the fetus at the time of gestation, when heart block usually develops. Second, differences in the clinical presentations of NLE (in utero vs. postnatal disease) cannot be attributed to differences in anti-Ro/SSA IgG subclasses. Finally, the subclass bound in the skin in SCLE is IgG1, a subclass capable of mediating tissue injury via complement or cellular effectors.     

The cytotoxic effect of neonatal lupus erythematosus and maternal sera on keratinocyte cultures is complement-dependent and can be augmented by ultraviolet irradiation

Summary To elucidate the role of autoantibodies and ultraviolet (UV) exposure in the pathogenesis of the skin lesions in neonatal lupus erythematostis (NLE). keratinocytes were cultured, as the target cells, from a patient with NLE and from a normal neonate. We demonstrated that the expression of nuclear/cytoplasmic Ro/SSA and La/SSB molecules on to the surface of NLE keratinocytes occurred to a much greater extent than that on normal keratinocytes. A dose of 200 ml/cm² UVB irradiation on NLE keratinocytes induced a 2.5–3-fold increase in Ro/SSA and La/SSB expression compared to non-irradiated cells. Sera derived from both the NLE patient and from his mother exhibited a cytotoxie effect on NLE keratinocytes, but not on control cells, in the presence of complement. Furthermore, the cytotoxieity of the sera was enhanced on UVB-irradiated NLE keratinocytes. whereas it had no cytotoxie efects on UVB-irradiated control cells. This suggests that the abnormal expression of both Ro/SSA and La/SSB on the surface membrane of NLE keratinocytes induces the autoantibodies and complements to injure the cells. This complement-mediated cytotoxic effect can be augmented by UV irradiation, a concept not incompatible with the exacerbation of the skin eruption in sun-exposed skin sites.     

Neonatal lupus erythematosus

Neonatal lupus Erythematosus (NLE) is a disorder characterized by maternal autoantibodies against RNA protein complex, Ro/SSA or SSB/La. These maternal IgG antibodies cross the placenta and potentially lead to fetal tissue damage and the clinical manifestations NLE. NLE is uncommon, affects females more than males, has no race predilection, and involves multiple organs. It has cutaneous manifestations similar to subacute cutaneous lupus erythematosus (SCLE). In addition to skin findings, patients with NLE have a significant risk of congenital heart block (CHB), a potentially fatal complication. Less frequently, hematologic and hepatic abnormalities occur. Approximately half of the reported cases have skin disease and half have CHB. Approximately 10% have both CHB and skin findings. The cutaneous, hematologic, and hepatic abnormalities are transient, clearing by 6 months of age. However, CHB is permanent and requires a pacemaker in many cases. The disorder results from the passive transfer of maternal autoantibodies, anti-RoSSA and anti-La/SSB. Sontheimer and McCauliffe reviewed the pathogenic role of anti-Ro antibody in NLE lesions and summarize evidence supporting its pathogenic role. Additional evidence suggests the possibility that Ro-antigen-specific T-cells may be present in SCLE patients and have the capacity to cause direct injury to the skin. McCuistion and Schoch first suggested this hypothesis in 1954 when they described an infant with LE skin findings born to a mother with systemic lupus erythematosus (SLE). Since this initial observation, a number of researchers have documented the role of maternal autoantibodies in the pathogenesis of this disorder. The true incidence of NLE is not known; however, it is known that NLE accounts for approximately 80% of all cases of CHB, and the incidence of CHB is 1 per 20,000 live births. Therefore, it can be assumed that the incidence of NLE is at least 1 per 12,500 live births.     

Neonatal Lupus Erythematosus Related to Maternal Leukocytoclastic Vasculitis

Abstract: Neonatal lupus erythemalosus (NLE) is an autoimmune disease whose major findings are skin lesions and congenital heart block. Affected infants have maternal, transplacentally acquired, autoantibodies to Ro/SSA, La/SSB, or U,-RNP antigens. Anti-Ro/SSA is the predominant autoantibody, present in about 95% of cases. Mothers of babies with NLE may be asymptomatic initially or may have Sjógrent syndrome, lupus erythematosus, overlap syndrome or, uncommonly, leukocytoclastic vasculitis. When evaluating a young woman with a cutaneous leucocytoclastic vasculitis, dermatologists should be aware of the possible presence of antibodies related to NLE. If any patient suffering a disorder related to NLE becomes pregnant, testing for autoantibodies and close obstetric prenatal care with fetal echocardiogram is necessary. In cases of fetal bradycardia, treatment with dexamethasone or betamethasone should be considered, as these drugs are accessible to the fetal circulation.     

Cutaneous neonatal lupus erythematosus: discordant expression in identical twins

BACKGROUND: Neonatal lupus erythematosus is a rare syndrome characterized essentially by cutaneous lesions and/or congenital heart block occurring in infants at birth, or shortly after. It is related to transplacental crossing of maternal auto antibodies (usually anti Ro/SS-A, La/SS-B or rarely anti-U(1) RNP) from the mother to the infant. Mothers of affected children have signs of systemic lupus erythematosus or other collagenosis or are asymptomatic. CASE REPORT: We report a case of neonatal lupus erythematosus in one identical twin, revealed at the age of 3 months by erythematous and annular cutaneous lesions of the face and limbs. These lesions were preceded at birth by an asymmetrical livedo pattern of the lower limbs. Her twin sister was unaffected but both infants had a high rate of anti-Ro/SSA antibodies. The diagnosis of neonatal lupus erythematosus permitted to reveal a biological lupus syndrome in their asymptomatic mother. Cutaneous lesions cleared almost completely within 1 year whereas antiRo/SSA antibodies disappeared. CONCLUSION: Cases of neonatal lupus erythematosus in twins are rare and mostly described in heterozygotic twins. Clinical discordance is usual and could partly be explained by genetic factors. In monozygotic twins, like in our case, chromosome X inactivation could be an explanation of the differences observed.     

Neonatal lupus erythematosus presenting as papules on the feet

We describe a case of neonatal lupus erythematosus in a 4‐week‐old male baby presenting with nodules/papules on the plantar surface of both feet. Skin histology of the right foot papule was consistent with lupus erythematosus. Annular lesions more typical of this condition then appeared later and maternal antibodies were positive for speckled antinuclear antibodies (1:5120), anti‐Ro/SSA and anti‐La/SSB(+), rheumatoid factor 1380.0 IU/mL. The patient had no evidence of cardiac, haematological or hepatobilary involvement. Although the mother was asymptomatic, the maternal grandmother had recently been diagnosed with Sjögren's syndrome.     

Immunogenetic study of three Japanese families with neonatal lupus erythematosus.

We encountered three Japanese families with neonatal lupus erythematosus. None of the three fathers showed any signs of collagen disease. The three mothers were found to suffer from Sjögren's syndrome; they all tested positive for anti-SSA and SSB antibodies and had lymphocyte infiltration into the small salivary gland. In two families, one child had neonatal lupus erythematosus while a sibling was normal; in the third family, both children had neonatal lupus erythematosus. Thus, a mother with positive anti-SSA and SSB antibodies can give birth to one infant with and one infant without or have two infants with neonatal lupus erythematosus. We conducted HLA typing of all 12 members of the three families in order to clarify the immunologic factors involved. We found no increased frequency of any HLA phenotype in the three mothers and their four children with neonatal lupus erythematosus; however, HLA-DR4 was present in three of the children with neonatal lupus erythematosus.     

Neonatal lupus erythematosus

Neonatal lupus erythematosus is associated with cutaneous lesions, CHB, hepatic disease, and thrombocytopenia. IgG antibodies to Ro and/or La cross the placenta and participate in the development of the clinical manifestations. Mothers of babies with NLE are likely to develop collagen vascular diseases with time. Infants with NLE are at risk to develop other autoimmune diseases during childhood or adolescence.     

Neonatal lupus erythematosus. A report of three cases associated with anti-Ro/SSA antibodies

Three patients had neonatal lupus erythematosus syndrome. All three infants were girls who presented with characteristic skin lesions but without evidence of congenital heart block. All three mothers were asymptomatic at the time of delivery and have remained so until the present time. All mothers were positive for anti-Ro/SSA antibodies, as were the infants prior to 6 months of age. Anti-La/SSB antibodies were not present in either the mothers or the infants. HLA typing revealed that two of the mothers were positive for B8 and DR3, while the third mother was positive for B8 and DR2. Two of the infants were positive for B8 and DR3, while the third infant was positive for DR2 only.     

Female predominance of immune response to SSA/Ro antigens and risk of neonatal lupus erythematosus

Eight-hundred and twenty-five patients attending the hospital with clinical signs and symptoms of collagen diseases were tested for anti-SSA/Ro antibody. The frequency of positivity to SSA/Ro was significantly higher in females, 11.0%, than in males, 3.2% (P less than 0.01). Five babies born to anti-SSA/Ro positive mothers all had neonatal lupus erythematosus and in one there were various cardiac abnormalities.     

13例新生儿红斑狼疮的临床特征、皮损后遗表现

【摘要】 目的 探讨新生儿红斑狼疮（NLE）的皮损后遗表现，分析可能的相关因素。方法 回顾2016—2020年首都儿科研究所附属儿童医院皮肤科收集并长期随访的13例NLE，分析患儿及母亲临床特征、患儿皮损后遗表现。结果 13例皮损发病时间为出生后0 ~ 120 d，平均15 d，随访时间15 ~ 43个月，皮损形态主要为环状红斑、斑丘疹、鳞屑，皮损消退时间2 ~ 18个月（平均7.4个月）。6例皮损消退后出现色素异常表现，3例同时出现色素减退和色素沉着，2例仅有色素减退，1例仅有色素沉着，1例色素减退患儿在随访18个月后色素减退复色，未见毛细血管扩张以及萎缩或瘢痕。8例患儿母亲孕前无异常，4例患儿母亲抗ANA、抗SSA/Ro、抗SSB/La抗体均阳性。结论 NLE的皮肤受累可出现后遗皮肤表现，常见为色素异常，多数长期未消退，应注意患儿母亲可能存在的潜在性免疫系统异常。