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Neonatal Lupus: What We Have Learned and Current Approaches to Care

  • Pediatric Rheumatology (S Ozen, Section Editor)
  • Published:
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Abstract

Neonatal lupus results from the passive transfer of autoantibodies; however, this transfer is not sufficient to cause disease. This article reviews clinical presentation with a focus on autoimmune-mediated congenital heart disease. Recent data looking for additional disease mechanisms and biomarkers as well as latest information on interventions will be reviewed. Our understanding of this rare disease is often dependent on patient participation in disease registries and biorepositories. Future participation in registries including descriptive as well as biophysical data is critical to our knowledge.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Litsey SE, Noonan JA, O’Connor WN, et al. Maternal connective tissue disease and congenital heart block. Demonstration of immunoglobulin in cardiac tissue. N Engl J Med. 1985;3129:98–100.

    Article  Google Scholar 

  2. Cimaz R, Spence DL, Hornberger L, et al. Incidence and spectrum of neonatal lupus erythematosus: a prospective study of infants born to mothers with anti-Ro autoantibodies. J Pediatr. 2003;142(6):678–83. This article is a prospective study which describes the incidence and types of neonatal lupus born to mothers with anti-Ro antibodies. Most data are from registries.

    Article  PubMed  Google Scholar 

  3. Franco HL, Weston WL, Peebles C, et al. Autoantibodies directed against sicca syndrome antigens in the neonatal lupus syndrome. J Am Acad Dermatol. 1981;4(1):67–72.

    Article  CAS  PubMed  Google Scholar 

  4. Neiman AR, Lee LA, Weston WL, et al. Cutaneous manifestations of neonatal lupus without heart block: characteristics of mothers and children enrolled in a national registry. J Pediatr. 2000;137(5):674–80.

    Article  CAS  PubMed  Google Scholar 

  5. Bouderlique C, Debillon T, Mesnard B, et al. Neonatal lupus presenting as telangiectasic and atrophic lesions. Pediatrie. 1990;45(4):251–4. Article in French 2.

    CAS  PubMed  Google Scholar 

  6. Guinovart RM, Vicente A, Rovira C, et al. Facial telangiectasia: an unusual manifestation of neonatal lupus erythematosus. Lupus. 2012;21(5):552–5.

    Article  CAS  PubMed  Google Scholar 

  7. Lin C, Shyur SD, Wu JY, et al.: Facial telangiectasia—an unusual complication of neonatal lupus erythematosus: report of one case. Acta Paediatr. Taiwan. 2004;45 (4):246–248.

  8. Thornton CM, Eichenfield LF, Shinall EA, et al. Cutaneous telangiectases in neonatal lupus erythematosus. J Am Acad Dermatol. 1995;33(1):19–25.

    Article  CAS  PubMed  Google Scholar 

  9. Heelan K, Watson R, Collins SM. Neonatal lupus syndrome associated with ribonucleoprotein antibodies. Pediatr Dermatol. 2013;30(4):416–23.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  Google Scholar 

  11. Chen CC, Lin K-L, Chen CL, et al. Central nervous system manifestations of neonatal lupus: a systematic review. Lupus. 2013;22:1484–8.

    Article  CAS  PubMed  Google Scholar 

  12. Askanase AD, Izmirly PM, Katholi M, et al. Frequency of neuro-psychiatric dysfunction in anti-SSA/SSB exposed children with and without neonatal lupus. Lupus. 2010;19:300–6.

    Article  CAS  PubMed  Google Scholar 

  13. Skog A, Tingstrom J, Salomonsson S, et al. Neurodevelopment in children with and without congenital heart block born to anti-Ro/SSA-positive mothers. Acta Pediatr. 2013;102:40–6. This is the only paper that describes neurodevelopmental outcomes of children with in utero anti-Ro antibodies comparing effects of congenital heart block to those children who had healthy hearts.

    Article  Google Scholar 

  14. Nalli C, Iodice A, Andreoli L, et al. The effects of lupus and antiphospholipid antibody syndrome on foetal outcomes. Lupus. 2014;23:507–17.

    Article  CAS  PubMed  Google Scholar 

  15. Izmirly PM, Buyon JP, Saxena A. Neonatal lupus: advances in understanding pathogenesis and identifying treatments of cardiac disease. Curr Opin Rheumatol. 2012;24:466–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Izmirly PM, Saxena A, Kim MY, et al. Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation. 2011;124(9):1927–35. This is an excellent description of factors both from the mother and the fetus that might alter outcomes for cardiac neonatal lupus in a heterogenous population.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Brito-Seron P, Izmirly PM, Ramos-Casals M, et al. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol. 2015;11(5):301–12.

    Article  Google Scholar 

  18. Brucato A, Frassi M, Franceschini F, et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by couterimmunoelectrophoresis: a prospective study. Arthritis Rheum. 2001;44:1832–5.

    Article  CAS  PubMed  Google Scholar 

  19. Costedoat-Chalumeau N, Amoura Z, Lupoglazoff JM, et al. Outcome of pregnancies in patients with anti-SSA/Ro antibodies: a study of 165 pregnancies with special focus on electrocardiographic variations in the children and comparison with a control group. Arthritis Rheum. 2004;50:2187–94.

    Google Scholar 

  20. Llanos C, Izmirly PM, Katholi M, et al. Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. Arthritis Rheum. 2009;60:3091–7.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rivera TL, Izmirly PM, Birnbaum BK, et al. Disease progression in mothers of children enrolled in the Research Registry for Neonatal Lupus. Ann Rheum Dis. 2009;68:828–35.

    Article  CAS  PubMed  Google Scholar 

  22. Clancy RM, Kapur RP, Molad Y, et al. Immunohistologic evidence supports apoptosis, IgG deposition, and novel macrophage/fibroblast crosstalk in the pathologic cascade leading to congenital heart block. Arthritis Rheum. 2004;50:173–82.

    Article  CAS  PubMed  Google Scholar 

  23. Scarsi M, Radice A, Pregnolato F, et al. Anti-Ro/SSA-p200 antibodies in the prediction of congenital heart block. An Italian multicenter cross-sectional study on behalf of the ‘Forum Interdisciplinare per la ricerca nelle Malattie Autoimmuni (FIRMA) group. Clin Exp Rheumatol. 2014;32:848–54.

    PubMed  Google Scholar 

  24. Jaeggi E, Laskin C, Hamilton R, et al. The importance of the level of maternal anti-Ro/SSA antibodies as a prognostic marker of the development of cardiac neonatal lupus erythematosus a prospective study of 186 antibody-exposed fetuses and infants. J Am Coll Cardiol. 2010;55:2778–84.

    Article  CAS  PubMed  Google Scholar 

  25. Lindip R, Arentz G, Thurgood LA, et al. Pathogenicity and proteomic signatures of autoantibodies to Ro and La. Immunol Cell Biol. 2012;90:304–9.

    Article  Google Scholar 

  26. Strandberg LS, Cui X, Rath A, et al. Congenital heart block maternal sera autoantibodies target an extracellular epitope on the alpha 1G T-type calcium channel in human fetal hearts. PLoS One. 2013;8, e72668. This paper describes the identification of a calcium channel autoantibody from maternal human serum that could account for changes in the conduction system. It has been unclear to date why anti-SSA/SSB antibodies specifically target the conduction system.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Clancy RM, Backer CB, Yi X, et al. Cytokine polymorphisms and histologic expression in autopsy studies: contribution of TNF-alpha and TGF-beta 1 to the pathogenesis of autoimmune-associated congenital heart block. J Immunol. 2003;171:3253–61.

    Article  CAS  PubMed  Google Scholar 

  28. Stevens AM, Hermes HM, Rutledge JC, et al. Myocaridal-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block. Lancet. 2003;362:1617–23.

    Article  PubMed  Google Scholar 

  29. Stevens AM, Hermes HM, Lambert NC, et al. Maternal and sibling microchimerism in twins and triplets discordant for neonatal lupus syndrome-congenital heart block. Rheumatology(Oxford). 2005;44:187–91.

    Article  CAS  Google Scholar 

  30. Saxena A, Izmirly PM, Han SW, et al. Serum biomarkers of inflammation, fibrosis, and cardiac function in facilitating diagnosis, prognosis, and treatment of anti-SSA/Ro-associated cardiac neonatal lupus. J Am Coll Cardiol. 2015;66:930–9. This is an excellent study describing potential biomarkers that can identify and assess risk for infants exposed to anti-SSA/Ro antibodies.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pisoni CN, Brucato A, Ruffatti A, et al. Failure of intravenous immunoglobulin to prevent congenital heart block: findings of a multicenter, prospective, observational study. Arthritis Rheum. 2010;62:1147–52.

    Article  CAS  PubMed  Google Scholar 

  32. Friedman DM, Llanos C, Izmirly PM, et al. Evaluation of fetuses in a study of intravenous immunoglobulin as a preventive therapy for congenital heart block: results of a multicenter, prospective, open-label clinical trail. Arthritis Rheum. 2010;62:1138–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Izmirly PM, Saxena A, Sahl S, 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. 2015;75(6):1161–6. This study demonstrates the lack of utility of fluorinated steroid treatment as an intervention in utero for autoimmune-mediated heart block.

    Article  PubMed  Google Scholar 

  34. 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;110:1542–8.

    Article  PubMed  Google Scholar 

  35. Brucato A, Ramoni V, Gerosa M et al. Congenital fetal heart block: a potential therapeutic role for intravenous immunoglobulin Obstet Gynecol 2011; 117(177).

  36. 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;57:715–23.

    Article  PubMed  Google Scholar 

  37. Cuneo BE, Lee M, Roberson D, et al. A management strategy for f or fetal immune-mediated atrioventricular block. J Matern Fetal Neonatal Med. 2010;23:1400–5. This paper describes a strategy for treating the fetus in utero including a biophysical profile and progression of intervention for heart failure and bradycardia.

    Article  PubMed  Google Scholar 

  38. Clowse ME, Madger L, Witter F, et al. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 2006;54:3640–7.

    Article  PubMed  Google Scholar 

  39. Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated with a reduce risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 2012; 126976–82. This paper describes the decreased rate of autoimmune-mediated heart block in mothers being treated with hydroxychloroquine and prompted the current interventional study of hydroxychloroquine in anti-Ro positive mothers during pregnancy.

  40. Bergman G, Eliasson H, Mohlkert LA, et al. Progression to first-degree heart block in preschool children exposed in utero to maternal anti-SSA/’Ro52 autoantibodies. Acta Paediatr. 2012;101:488–93.

    Article  CAS  PubMed  Google Scholar 

  41. Bergman G, Skog A, Tingstrom J, et al. Late development of complete atrioventricular block may be immune mediated and congenital in origin. Acta Paediatr. 2014;103:275–81.

    Article  CAS  PubMed  Google Scholar 

  42. Skog A, Eliasson H, Tingstrom J, et al. Long term growth of children with autoantibody mediated congenital heart block. Acta Paediatr. 2013;102:718–26.

    Article  PubMed  Google Scholar 

  43. Davey DL, Bratton SL, Bradkley DJ, et al. Relation of maternal anti-Ro/La antibodies to aortic dilation in patients with congenital complete heart block. Am J Cardiol. 2011;108:561–4.

    Article  PubMed  Google Scholar 

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Correspondence to Marisa S. Klein-Gitelman.

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Conflict of Interest

MSKG reports grants from Alliance for Lupus Research, Lupus Foundation of America, and NIAMS, outside the submitted work.

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This article does not contain any studies with human or animal subjects performed by the author (MSKG).

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This article is part of the Topical Collection on Pediatric Rheumatology

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Klein-Gitelman, M.S. Neonatal Lupus: What We Have Learned and Current Approaches to Care. Curr Rheumatol Rep 18, 60 (2016). https://doi.org/10.1007/s11926-016-0610-z

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  • DOI: https://doi.org/10.1007/s11926-016-0610-z

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