Neonatal lupus erythematosus: A narrative review




antibody, congenital atrioventricular block, corticosteroid, neonatal lupus erythematosus, pacemaker


Introduction: Neonatal lupus erythematosus (NLE) is characterized by the transplacental passage of maternal antibodies, mainly anti-Sjogren’s syndrome A/Ro (anti-SSA/Ro) and anti-Sjogren’s syndrome B/La (anti-SSB/La), which bind to the developing fetal tissues. Seropositive mothers may have a diagnosed disease, such as Sjögren’s syndrome, systemic lupus erythematosus, or undifferentiated connective tissue disease, but in 25─60% of cases, they are asymptomatic at the time of childbirth.
Objectives: This article aimed to provide a narrative review of the current state of knowledge on NLE.
Development: The clinical spectrum of NLE includes both reversible and irreversible features. Reversible clinical features, like cutaneous lesions, hematological and pulmonary abnormalities, and hepatobiliary dysfunction, disappear spontaneously as autoantibody levels decrease in the bloodstream. The most commonly reported NLE manifestation is cardiac disease. Injury to the cardiac conduction tissue may lead to defects, such as congenital atrioventricular (AV) block, which is the most severe and, in some cases, lethal NLE manifestation. NLE may also have an impact on the myocardium and endocardium, with maternal antibodies being responsible for endocardial fibroelastosis. Immune-mediated AV block may benefit from in-utero treatment with steroids. Hydroxychloroquine may also be prescribed to women with immune-mediated disorders in the preconception period.
Conclusions: The management of infants affected with NLE should be performed in a tertiary care center. Postnatal pacemaker insertion may be indicated in the presence of irreversible AV block or heart failure. Erythrocyte or platelet transfusions, corticosteroids, or intravenous immunoglobulin may be indicated to treat severe disease manifestations.


Download data is not yet available.


Erden A, Fanouriakis A, Kiliç L, et al. Geoepidemiology and clinical characteristics of neonatal lupus erythematosus: a systematic literature review of individual patients’ data. Turk J Med Sci 2020;50(1):281-290. DOI:

Li X, Huang X, Lu H. Two case reports of neonatal autoantibody-associated congenital heart block. Medicine (Baltimore) 2018;97(45):e13185. DOI:

Derdulska JM, Rudnicka L, Szykut-Badaczewska A, et al. Neonatal lupus erythematosus - practical guidelines. J Perinat Med 2021;49(5):529-538. DOI:

Vanoni F, Lava SAG, Fossali EF, et al. Neonatal Systemic Lupus Erythematosus Syndrome: a Comprehensive Review. Clin Rev Allergy Immunol 2017;53(3):469-476. DOI:

Gryka-Marton M, Szukiewicz D, Teliga-Czajkowska J, et al. An Overview of Neonatal Lupus with Anti-Ro Characteristics. Int J Mol Sci 2021;22(17). DOI:

Bin S, Heng R, Im S. Complete heart block in neonatal lupus: a forgotten cause of fetal bradycardia. BMJ Case Rep 2021;14(11). DOI:

Rumancik B, Haggstrom AN, Ebenroth ES. Neonatal lupus with left bundle branch block and cardiomyopathy: a case report. BMC Cardiovasc Disord 2020;20(1):352. DOI:

Lee LA. The clinical spectrum of neonatal lupus. Arch Dermatol Res 2009;301(1):107-110. DOI: 10.1007/s00403-008-0896-4.

Akbariasbagh P, Sheikh M, Akbariasbagh N, et al. Extensive aortic aneurysm associated with neonatal lupus erythematosus. Ann Pediatr Cardiol 2016;9(2):201-202. DOI:

Izmirly PM, Buyon JP, Saxena A. Neonatal lupus: advances in understanding pathogenesis and identifying treatments of cardiac disease. Curr Opin Rheumatol 2012;24(5):466-472. DOI:

Izmirly P, Saxena A, Buyon JP. Progress in the pathogenesis and treatment of cardiac manifestations of neonatal lupus. Curr Opin Rheumatol 2017;29(5):467-472. DOI:

Teixeira V, Gonçalo M. [Neonatal lupus erythematosus - review of pathophysiology and clinical implications]. Acta Reumatol Port 2012;37(4):314-323.

Morel N, Georgin-Lavialle S, Levesque K, et al. [Neonatal lupus syndrome: Literature review]. Rev Med Interne 2015;36(3):159-166. DOI:

Assari R, Ziaee V, Moradinejad MH, et al. Neonatal Lupus erythematosus Following Rheumatoid Arthritis: Case Report and Literature Review. Iran J Pediatr 2014;24(4):445-448.

Luo Y, Zhang L, Fei Y, et al. Pregnancy outcome of 126 anti-SSA/Ro-positive patients during the past 24 years--a retrospective cohort study. Clin Rheumatol 2015;34(10):1721-1728. DOI:

Spence D, Hornberger L, Hamilton R, et al. Increased risk of complete congenital heart block in infants born to women with hypothyroidism and anti-Ro and/or anti-La antibodies. J Rheumatol 2006;33(1):167-170.

Coelho R, Ferreira M, Ferreira M, et al. [Neonatal lupus erythematosus]. Acta Med Port 2007;20(3):229-232.

Oliveira FR, Valim V, Pasoto SG, et al. 2021 recommendations of the Brazilian Society of Rheumatology for the gynecological and obstetric care of patients with Sjogren’s syndrome. Adv Rheumatol 2021;61(1):54. DOI:

Hansahiranwadee W. Diagnosis and Management of Fetal Autoimmune Atrioventricular Block. Int J Womens Health 2020;12633-639. DOI:

Pedra S, Zielinsky P, Binotto CN, et al. Brazilian Fetal Cardiology Guidelines - 2019. Arq Bras Cardiol 2019;112(5):600-648. DOI:

Cuneo BF, Lee M, Roberson D, et al. A management strategy for fetal immune-mediated atrioventricular block. J Matern Fetal Neonatal Med 2010;23(12):1400-1405. DOI:

Klein-Gitelman MS. Neonatal Lupus: What We Have Learned and Current Approaches to Care. Curr Rheumatol Rep 2016;18(9):60. DOI:

Martin TA. Congenital heart block: current thoughts on management, morphologic spectrum, and role of intervention. Cardiol Young 2014;24 Suppl 241-46. DOI:

Hulsmann AR, Oranje AP. Educational paper: neonatal skin lesions. Eur J Pediatr 2014;173(5):557-566. DOI:

Li YQ, Wang Q, Luo Y, et al. Neonatal lupus erythematosus: a review of 123 cases in China. Int J Rheum Dis 2015;18(7):761-767. DOI:

Sitthinamsuwan P, Nitiyarom R, Chairatchaneeboon M, et al. Histiocytoid neutrophilic dermatitis, an unusual histopathology in neonatal lupus erythematosus. J Cutan Pathol 2015;42(12):996-999. DOI:

Lee SH, Roh MR. Targetoid lesions and neutrophilic dermatosis: an initial clinical and histological presentation of neonatal lupus erythematosus. Int J Dermatol 2014;53(6):764-766. DOI:

Méndez Sánchez A, Garrido García E, García Fernández J, et al. [Neonatal lupus erythematosus: Suspect and diagnosis]. An Pediatr (Engl Ed) 2021. DOI:

Lee LA, Sokol RJ, Buyon JP. Hepatobiliary disease in neonatal lupus: prevalence and clinical characteristics in cases enrolled in a national registry. Pediatrics 2002;109(1):E11. DOI:

Zuppa AA, Riccardi R, Frezza S, et al. Neonatal lupus: Follow-up in infants with anti-SSA/Ro antibodies and review of the literature. Autoimmun Rev 2017;16(4):427-432. DOI:

Halder R, Malik R, Kashyap R. Warm antibody hemolytic anemia-a rare presentation of neonatal lupus. Lupus 2017;26(6):661-663. DOI:

Watson RM, Lane AT, Barnett NK, et al. Neonatal lupus erythematosus. A clinical, serological and immunogenetic study with review of the literature. Medicine (Baltimore) 1984;63(6):362-378.

Pereira S, Flor-de-Lima F, Soares H, et al. Pulmonary involvement in neonatal lupus: a challenging diagnosis - case report and literature review. Acta Reumatol Port 2018;43(3):230-234.

Maltret A, Morel N, Levy M, et al. Pulmonary hypertension associated with congenital heart block and neonatal lupus syndrome: A series of four cases. Lupus 2021;30(2):307-314. DOI:

Hunter LE, Simpson JM. Atrioventricular block during fetal life. J Saudi Heart Assoc 2015;27(3):164-178. DOI:

Neonatal lupus: Epidemiology, pathogenesis, clinical manifestations, and diagnosis. Uptodate, 2022. at,%20pathogenesis,%20clinical%20manifestations,%20and%20diagnosis&source=search_result&selectedTitle=1~36&usage_type=default&display_rank=1.

Donofrio MT, Moon-Grady AJ, Hornberger LK, et al. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation 2014;129(21):2183-2242. DOI:

Friedman DM, Kim MY, Copel JA, et al. Prospective evaluation of fetuses with autoimmune-associated congenital heart block followed in the PR Interval and Dexamethasone Evaluation (PRIDE) Study. Am J Cardiol 2009;103(8):1102-1106. DOI:

Buyon JP, Clancy RM, Friedman DM. Cardiac manifestations of neonatal lupus erythematosus: guidelines to management, integrating clues from the bench and bedside. Nat Clin Pract Rheumatol 2009;5(3):139-148. DOI:

Izmirly PM, Saxena A, Sahl SK, et al. Assessment of fluorinated steroids to avert progression and mortality in anti-SSA/Ro-associated cardiac injury limited to the fetal conduction system. Ann Rheum Dis 2016;75(6):1161-1165. DOI:

Cuneo BF, Sonesson SE, Levasseur S, et al. Home Monitoring for Fetal Heart Rhythm During Anti-Ro Pregnancies. J Am Coll Cardiol 2018;72(16):1940-1951. DOI:

Groves AM, Allan LD, Rosenthal E. Therapeutic trial of sympathomimetics in three cases of complete heart block in the fetus. Circulation 1995;92(12):3394-3396. DOI:

Jaeggi ET, Fouron JC, Silverman ED, et al. Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation 2004;110(12):1542-1548. DOI:

Guettrot-Imbert G, Cohen L, Fermont L, et al. A new presentation of neonatal lupus: 5 cases of isolated mild endocardial fibroelastosis associated with maternal Anti-SSA/Ro and Anti-SSB/La antibodies. J Rheumatol 2011;38(2):378-386. DOI:

Trucco SM, Jaeggi E, Cuneo B, et al. Use of intravenous gamma globulin and corticosteroids in the treatment of maternal autoantibody-mediated cardiomyopathy. J Am Coll Cardiol 2011;57(6):715-723. DOI:

Jaeggi ET, Hamilton RM, Silverman ED, et al. Outcome of children with fetal, neonatal or childhood diagnosis of isolated congenital atrioventricular block. A single institution’s experience of 30 years. J Am Coll Cardiol 2002;39(1):130-137. DOI:

Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 2012;126(1):76-82. DOI:

Izmirly PM, Kim MY, Llanos C, et al. Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis 2010;69(10):1827-1830. DOI:

Barsalou J, Costedoat-Chalumeau N, Berhanu A, et al. Effect of in utero hydroxychloroquine exposure on the development of cutaneous neonatal lupus erythematosus. Annals of the Rheumatic Diseases 2018;77(12):1742-1749. DOI:

Eliasson H, Sonesson SE, Sharland G, et al. Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients. Circulation 2011;124(18):1919-1926. DOI:

Martin V, Lee LA, Askanase AD, et al. Long-term followup of children with neonatal lupus and their unaffected siblings. Arthritis Rheum 2002;46(9):2377-2383. DOI:

Congenital third degree (complete) atrioventricular block. 2022. at




How to Cite

Marques AR, Rocha G, Soares P, Rodrigues M, Pimenta J. Neonatal lupus erythematosus: A narrative review. REVNEC [Internet]. 2022Dec.27 [cited 2024Apr.15];31(4):364-76. Available from:



Review Articles