Cutaneous Neonatal Lupus Research Articles

Cutaneous neonatal lupus in patients with skin of color: A retrospective cohort study from a national registry

Cutaneous neonatal lupus in patients with skin of color: A retrospective cohort study from a national registry

Neonatal Lupus Erythematosus: A Case Report and Review of the Literature

Neonatal lupus erythematosus (NLE) is a rare autoimmune condition caused by transplacental passage of maternal IgG autoantibodies to the fetus. It often presents with erythematous annular lesions on the scalp and periorbital area that appear after exposure to sunlight. Clinicians should be aware of the broad manifestations of neonatal lupus erythematosus, including cutaneous, cardiac, hematologic, hepatic and neurological manifestations. We present a case of cutaneous neonatal lupus erythematosus with rare central nervous system findings and perform a literature review on the subject.

Maternal and infant outcomes of pregnancy associated with anti-SSA/RO antibodies: a systematic review and meta-analysis

ObjectiveThe relationship between anti-SSA/RO antibodies and pregnancy has been reported previously, and we aim to visualize the rates of maternal and infant outcomes with anti-SSA/RO.MethodsWe systematically searched records from Pubmed, Cochrane, Embase, and Web of Science databases, pooled incidence rates of adverse outcomes of pregnancy, and 95% confidence intervals (CIs) were performed with RStudio.ResultsA total of 890 records comprising 1675 patients and 1920 pregnancies were searched from the electronic databases. For maternal outcomes, the pooled estimate rates were 4% for termination of pregnancy, 5% for spontaneous abortion, 26% for preterm labor, and 50% for cesarean operation. While for fetal outcomes, the pooled estimate rates were 4% for perinatal death, 3% for intrauterine growth retardation, 6% for endocardial fibroelastosis, 6% for dilated cardiomyopathy, 7% for congenital heart block, 12% for congenital heart block recurrence, 19% for cutaneous neonatal lupus erythematosus, 12% for hepatobiliary disease and 16% for hematological manifestations. A subgroup analysis of congenital heart block prevalence was performed, diagnostic method and study region were found to affect heterogeneity to some extent.ConclusionCumulative analysis of data from real-world studies confirmed adverse pregnancy outcomes of women with anti-SSA/RO, serves as a reference and a guide for the diagnosis and subsequent treatment of these women, thereby enhancing maternal and infant health. Additional studies with real-world cohorts are required to validate these results.

Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers

BackgroundExperimental and clinical evidence support the role of macrophage Toll-like receptor signaling in maternal anti-SSA/Ro–mediated congenital heart block (CHB). ObjectivesHydroxychloroquine (HCQ), an orally administered Toll-like receptor antagonist widely used in lupus including during pregnancy, was evaluated for efficacy in reducing the historical 18% recurrence rate of CHB. MethodsThis multicenter, open-label, single-arm, 2-stage clinical trial was designed using Simon’s optimal approach. Anti-SSA/Ro–positive mothers with a previous pregnancy complicated by CHB were recruited (n = 19 Stage 1; n = 35 Stage 2). Patients received 400 mg daily of HCQ prior to completion of gestational week 10, which was maintained through pregnancy. The primary outcome was 2° or 3° CHB any time during pregnancy, and secondary outcomes included isolated endocardial fibroelastosis, 1° CHB at birth and skin rash. ResultsBy intention-to-treat (ITT) analysis, 4 of 54 evaluable pregnancies resulted in a primary outcome (7.4%; 90% confidence interval: 3.4% to 15.9%). Because 9 mothers took potentially confounding medications (fluorinated glucocorticoids and/or intravenous immunoglobulin) after enrollment but prior to a primary outcome, to evaluate HCQ alone, 9 additional mothers were recruited and followed the identical protocol. In the per-protocol analysis restricted to pregnancies exposed to HCQ alone, 4 of 54 (7.4%) fetuses developed a primary outcome as in the ITT. Secondary outcomes included mild endocardial fibroelastosis (n = 1) and cutaneous neonatal lupus (n = 4). ConclusionsThese prospective data support that HCQ significantly reduces the recurrence of CHB below the historical rate by >50%, suggesting that this drug should be prescribed for secondary prevention of fetal cardiac disease in anti-SSA/Ro-exposed pregnancies. (Preventive Approach to Congenital Heart Block With Hydroxychloroquine [PATCH]; NCT01379573)

Raccoon eyes in cutaneous neonatal lupus syndrome.

Raccoon eyes in cutaneous neonatal lupus syndrome.

Pregnancy outcomes in mixed connective tissue disease: a multicentre study

In this study we aimed to investigate foetal and maternal pregnancy outcomes from a large multicentre cohort of women diagnosed with MCTD and anti-U1RNP antibodies. This multicentre retrospective cohort study describes the outcomes of 203 pregnancies in 94 consecutive women ever pregnant who fulfilled the established criteria for MCTD with confirmed U1RNP positivity. The foetal outcomes in 203 pregnancies were as follows: 146 (71.9%) live births, 38 (18.7%) miscarriages (first trimester pregnancy loss of <12 weeks gestation), 18 (8.9%) stillbirths (pregnancy loss after 20 weeks gestation) and 11 (5.4%) cases with intrauterine growth restriction. Maternal pregnancy outcomes were as follows: 8 (3.9%) developed pre-eclampsia, 2 (0.9%) developed eclampsia, 31 (15.3%) developed gestational hypertension and 3 (1.5%) developed gestational diabetes. Women with MCTD and aPL and pulmonary or muscular involvement had worse foetal outcomes compared with those without. Moreover, we report a case of complete congenital heart block (0.45%) and a case of cutaneous neonatal lupus, both born to a mother with positive isolated anti-U1RNP and negative anti-Ro/SSA antibodies. In our multicentre cohort, women with MCTD had a live birth rate of 72%. While the true frequency of heart block associated with anti-U1RNP remains to be determined, this study might raise the consideration of echocardiographic surveillance in this setting. Pregnancy counselling should be considered in women with MCTD.

Effect of in utero hydroxychloroquine exposure on the development of cutaneous neonatal lupus erythematosus

ObjectiveCutaneous neonatal lupus (cNL) occurs in possibly 5%–16% of anti-Ro±anti-La antibody–exposed infants. Data suggest in utero exposure to hydroxychloroquine (HCQ) may prevent cardiac NL. The aim was to assess whether...

Neonatal lupus erythematosus.

Neonatal lupus (NL), a passively-acquired autoimmune disease associated with maternal anti-SSA antibody, presents both cardiac manifestations such as cardiac NL and non-cardiac manifestations including rashes, cytopenia, and hepatic abnormalities. Cardiac NL, occurring in 1-2% of anti-SS-A antibody-positive mothers, is a life-threatening complication with a mortality rate of 20% and a pacemaker implantation rate of 70%. In contrast, cutaneous NL, which is more common than cardiac NL, usually resolves in six months. Since half of NL cases occur in asymptomatic mothers, if an infant presents characteristic cutaneous or cardiac manifestations of NL, the mother should be tested for anti-SS-A antibody. In mothers positive for anti-SS-A antibody, the risk of having a child with cardiac NL increases ten-fold and five-fold for a previous child with cardiac NL and cutaneous NL, respectively. A joint American, British, and French retrospective study of NL registries showed that hydroxychloroquine (HCQ) reduced the cardiac NL risk in subsequent pregnancies in mothers who previously had a child with cardiac NL. A prospective open-label study to confirm this effect is being undertaken in the USA. A similar prospective multi-center study will be undertaken in Japan. Establishing a Japanese registry of children with NL and subsequent pregnancies of their mothers will help promote clinical research in NL in Japan.

A 10-year retrospective study of neonatal lupus erythematous in China.

Neonatal lupus erythematosus (NLE) is not a common disease. The death rate of complete congenital heart block (CCHB), which is the most severe clinical manifestation, is as high as 20% to 30%, so early recognition of infants at risk is important. To investigate the clinical features and long-term prognosis of NLE. Twenty-five cases with NLE were reviewed. The clinical manifestations of patients and their mothers were summarized and analyzed. Autoantibodies were detected, and long-term follow-up was carried out. There were 25 patients (male:female ratio of 11:14). CCHB was detected in only 3 of the 25 patients (12%). Cutaneous neonatal lupus erythematosus (CNLE) was seen in 22 of the 25 patients (88%). Eight babies were treated with intravenous immunoglobulin (IVIG), five of whom had a prolonged PR interval that reverted to normal sinus rhythm. During the follow-up of the patients, we found only two patients with CCHB without a pacemaker, who both exhibited growth delay. One patient with CCHB without a pacemaker died. Children with NLE have an excellent outcome when only skin lesions are present. Even the hepatic, hematological and neurological abnormalities are transient, with generally good outcomes. IVIG might have some effectiveness due to enhanced anti-inflammatory activity to treat early diseases that may be reversible (e.g. prolonged PR interval). The long-term prognosis for patients with NLE is still under investigation, and some infants with NLE may progress to other autoimmune diseases later in childhood.

Autism spectrum disorders in babies born to mothers with antiphospholipid syndrome

ObjectivesTo evaluate the outcomes of babies born to mothers with primary antiphospholipid syndrome and to compare to the outcomes of babies of mothers with systemic lupus erythematosus. MethodsA retrospective study from 2003 to 2010 assessing the clinical characteristics and psychomotor development, as well as the immunological data, of children born to mothers with antiphospholipid syndrome (APS) (group 1) and systemic lupus erythematosus (group 2). ResultsGroup 1 consisted of 36 children born to mothers (n = 26) with a primary APS. Autism spectrum disorders occurred in 3 children from group 1 and all of them had persistent anti-β2GP1 IgG antibodies.Group 2 consisted of 12 children born to mothers (n = 9) with lupus erythematosus. Three children experienced cutaneous neonatal lupus, but there were no neurodevelopmental disorders. Comparing children of groups 1 and 2, no significant difference was found with regard to the parameters at birth or during follow-up. The children in group 2 had antinuclear antibodies more frequently (p < 0.05). ConclusionAutism spectrum disorders could be observed in babies born to mothers with antiphospholipid syndrome, but there is no risk of thrombosis. Key messagesNeonatal lupus is well-known complication in children born to mothers with systemic lupus erythematosus, but there is no risk of thrombosis in APS-exposed children.In children of APS mothers the rate of prematurity and small-for-gestational age weight remain high even in treated pregnancy.The presence of several cases of autism spectrum disorders in APS-exposed children could be related to mother's antibodies exposition, but need to be confirmed.

Cutaneous neonatal lupus: a case report and review of the literature

Cutaneous neonatal lupus: a case report and review of the literature

FRI0292 Children born to mothers with sle: no increase in males and hydroxychloroquine does not protect against neonatal lupus

BackgroundRecent Canadian data suggested an increased male:female ratio in children born to women with SLE1. However results combined from PROMISSE and RRNL data demonstrated no ignificant gender difference2 but reported...

Cutaneous neonatal lupus with cutis marmorata telangiectatica congenita-like lesions

Neonatal lupus is a rare disease caused by the transplacental transfer of maternal autoantibodies to the foetus, characterized by transient clinical manifestations such as cutaneous, haematological, and hepatobiliary events or permanent such as congenital heart block. The typical cutaneous manifestations include erythematous, scaly, annular or arched lesions on the face, with slight central atrophy and photosensitivy, clinically and histologically similar to subacute cutaneous lupus. However, in some cases, the lesions may resemble those in cutis marmorata telangiectatica congenita, although this phenomenon is rare and only eight such cases have been reported to date. We report a case of cutaneous neonatal lupus with atypical lesions on the limbs, which had a reddish-purple marbled appearance, resembling the lesions in cutis marmorata telangiectatica congenita.

AB1211 Newborns of mothers with autoimmune disease. Outcome in a regional hospital

BackgroundPregnant women with autoimmune disease (AID), particularly systemic lupus erythematosus (SLE), have increased risks of disease exacerbation, pre/eclampsia and other maternal and fetal complications. Low birth weight (LBW) for gestational...

Preferential transmission of genetic risk variants of candidate loci at 6p21 from asymptomatic grandparents to mothers of children with neonatal lupus

Neonatal lupus (NL) occurs in fetuses exposed to maternal anti-SSA/Ro and/or anti-SSB/La antibodies, although the mothers themselves may not manifest any clinical disease. A focus on transmission of risk factors for NL from maternal grandparents to mothers of children with NL may yield dividends toward understanding the aggregation of autoantibodies and genetic factors in affected families. This study was perforned to determine the role of maternal grandparents in the development of the autoimmune phenotype of mothers of children with NL. Fifty-one mothers of children with cardiac and/or cutaneous NL, 48 maternal grandmothers, and 35 maternal grandfathers in the Research Registry for Neonatal Lupus were interrogated for clinical symptoms by questionnaire and underwent laboratory assessments, including determination of anti-SSA/Ro and anti-SSB/La antibody status (by enzyme-linked immunosorbent assay) and genotype at rs1800629 (TNFα) and rs7775397 (C6orf10) (allelic discrimination). The transmission disequilibrium test (TDT) was computed to test for nonrandom transmission from maternal grandparents to mothers of children with NL. The common phenotypic feature in mothers of children with NL was the autoantibody and not the clinical profile; 7 had lupus, 14 had Sjögren's syndrome, 7 had both, and 23 were asymptomatic. Mothers of children with NL were significantly enriched for the risk alleles at both TNFα and C6orf10. The grandparents of children with NL carried minimal burden for autoimmune disease or abnormal antibody production and were not enriched in the genetic risk factors. However, the TDT analysis showed significant excess transmission of the risk alleles at both TNFα (odds ratio [OR] 6.67, P = 3.93 × 10(-4) ) and C6orf10 (OR 35.0, P = 3.74 × 10(-5) ) to mothers of children with NL. Mothers of children with NL are enriched for the TNFα and C6orf10 risk alleles, which are preferentially inherited from the asymptomatic maternal grandparents. These findings support the hypothesis that the development of NL and genetic etiology are multigenerational.

Cutaneous Neonatal Lupus Erythematosus Associated with Brain Infarction

Neonatal lupus erythematosus (NLE) is an acquired autoimmune disorder caused by the transplacental passage of maternal autoantibodies, usually anti-Ro/SSA or anti-La/SSB antibodies, and less commonly U1-ribonucleoprotein. NLE usually involves a single organ, but multiple organ involvement has also been reported. Manifestations of NLE may include cutaneous lesions, congenital heart block, hematological diseases (anemia, thrombocytopenia, neutropenia), hepatic diseases (hepatitis, hepatosplenomegaly, cholestasis), and neurological diseases. Neurological involvement is very rare in infants with NLE. Here, we report a 2-day-old female neonate, born to a clinically asymptomatic mother, presenting with cutaneous lupus lesions and brain infarction as a neurological disease.

Neonatal lupus: clinical features and risk of congenital cardiac heart block in newborns from mothers with anti Ro/SSA antibodies

OBJECTIVE: To assess the prevalence of Congenital Heart Block (CHB) in newborns from anti Ro/SS-A antibodies positive mothers affected by connective tissue diseases (CTD) and to evaluate the prevalence of other manifestations of Neonatal Lupus (NL) and the electrocardiographic abnormalities. METHODS: A prospective study was conducted on 100 anti Ro/SS-A positive mothers that were followed before and during their 118 pregnancies (4 twin pregnancies and 18 second pregnancies). Counterimmunoelectroforesis (CIE) and immunoblot (IB) were used to test antibodies to extractable nuclear antigens (ENA). RESULTS: Only 2 cases of CHB (1.8%) were found among the 112 living newborns. In one case the mother with primary Sjögren's Syndrome (pSS) was anti Ro 60 and 52kD positive while in the other case the mother affected by undifferentiated connective tissue disease (UCTD) was anti Ro 60kD and anti La positive. No fetal death was due to CHB. There were no cutaneous rashes at birth while mild hepatic enzyme alterations were observed in 21 (68%) of the 31 tested newborns. In 22 healthy newborns an ECG have been registered and in 4 cases (18.2%) sinus bradycardia was found. During the follow up 7 suckling showed Cutaneous Neonatal Lupus. Moreover a six month girl developed Kawasaki Syndrome. CONCLUSIONS: The risk of delivering a child with CHB is 1.8% in anti Ro/SS-A positive mothers with CTD. This finding is extremely important in the preconceptional counseling of anti-Ro/SS-A positive women. Furthermore mild electrocardiographic abnormalities may be found in their healthy newborns.

Pregnancy outcome in anti ro positive women – outcomes of a targeted approach

Anti Ro antibodies are relatively common and may be detected in up to 1–2% of randomly tested pregnant women. 50% of these women are otherwise asymptomatic and the remaining may...

Doppler fetal mechanical PR interval prolongation with positive maternal anti‐RNP but negative SSA/Ro and SSB/La auto‐antibodies

Cutaneous neonatal lupus can occur with negative SSA/Ro or SSB/La but positive non-SSA/SSB ribonucleoprotein (RNP) maternal autoantibodies (Provost et al., 1987). No fetal-cardiac manifestations, however, have been reported in association with isolated maternal RNP autoantibodies. We report the first association of transient first-degree atrioventricular block (AVB) in a fetus exposed to maternal anti-RNP in the absence of SSA/Ro-SSB/La autoantibodies.

Cutaneous Neonatal Lupus Erythematosus and Risk for Heart Block in Subsequent Pregnancy

Cutaneous disease and heart block are the major manifestations associated with passive transfer of maternal autoantibodies, particularly anti-Ro/SS-A.