Cutaneous Lupus Erythematosus During the Neonatal and Childhood Periods

  • Lela A. Lee


Systemic Lupus Erythematosus Chronic Granulomatous Disease Heart Block Hepatobiliary Disease Congenital Heart Block 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander E, Buyon JP, Provost TT, Guarnieri T (1992) Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro electrophysiologic and immunocytochemical studies. Arthritis Rheum 35:176–189Google Scholar
  2. Borda E, Sterin-Borda L (2001) Autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor in children with congenital heart block. J Autoimmun 16:143–150CrossRefPubMedGoogle Scholar
  3. Boutjdir M, Chen L, Zhang ZH, Tseng CE, El-Sherif N, Buyon JP (1998) Serum and immunoglobulin G from the mother of a child with congenital heart block induce conduction abnormalities and inhibit L-type calcium channels in a rat heart model. Pediatr Res 44:11–19PubMedGoogle Scholar
  4. Buyon JP, Slade SG, Reveille JD, Hamel JC, Chan EK (1994). Autoantibody responses to the “native”52-kDa SS-A/Ro protein in neonatal lupus syndromes, systemic lupus erythematosus, and Sjögren’s syndrome. J Immunol 152:3675–3684PubMedGoogle Scholar
  5. Buyon JP, Tseng CE, Di Donato F, Rashbaum W, Morris A, Chan EKL (1997) Cardiac expression of 52 β, an alternative transcript of the congenital heart block-associated 52-kd SS-A/Ro autoantigen, is maximal during fetal development. Arthritis Rheum 40:655–660PubMedGoogle Scholar
  6. Buyon JP, Hiebert R, Copel J, Craft J, Friedman D, Katholi M, Lee LA, Provost TT, Reichlin M, Rider L, Rupel A, Saleeb S, Weston WL, Skovron ML (1998) Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrencerates obtained from a national neonatal lupus registry. J Am Coll Cardiol 31:1658–1666CrossRefPubMedGoogle Scholar
  7. Clancy RM, Backer CB, Yin X, Kapur RP, Molad Y, Buyon JP (2003) 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 171:3252–3261Google Scholar
  8. Copel JA, Buyon JP, Kleinman CS (1995) Successful in utero therapy of fetal heart block. Am J Obstet Gynecol 17:1384–1390CrossRefGoogle Scholar
  9. David-Bajar KM, Bennion SD, DeSpain JD, Golitz LE, Lee LA (1992) Clinical, histologic, and immunofluorescent distinctions between subacute cutaneous lupus erythematosus and discoid lupus erythematosus. J Invest Dermatol 99: 251–257CrossRefPubMedGoogle Scholar
  10. Eftekhari P, Salle L, Lezoualch F, Mialet J, Gastineau M, Briand JP, Isenberg DA, Fournie GJ, Argibay J, Fischmeister R, Muller S, Haebeke J (2000) Anti-SSA/Ro52 autoantibodies blocking the cardiac 5-HT4 serotoninergic receptor could explain neonatal lupus congenital heart block. Eur J Immunol 30: 2782–2790CrossRefPubMedGoogle Scholar
  11. Eftekhari P, Roegel JC, Lezoualc’h F, Fischmeister R, Imbs JL, Hoebeke J (2001) Induction of neonatal lupus in pups of mice immunized with synthetic peptides derived from amino acid sequences of the serotoninergic 5-HT4 receptor. Eur J Immunol 31:573–579CrossRefPubMedGoogle Scholar
  12. Eronen M, Siren MK, Ekblad H, Tikanoja T, Julkunen H, Paavilainen T (2000) Short-and long-term outcome of children with congenital complete heart block diagnosed in utero or as a newborn. Pediatrics 106:86–91CrossRefPubMedGoogle Scholar
  13. Font J, Cervera R, Espinosa G, Pallares L, Ramos-Casals M, Jimenez S, Garcio-Carrasco M, Seisdedas L, Ingelmo M (1998) Systemic lupus erythematosus (SLE) in childhood: analysis of clinical and immunological findings in 34 patients and comparison with SLE characteristics in adults. Ann Rheum Dis 57:456–459PubMedGoogle Scholar
  14. Fraire-Velazquez S, Herrera-Esparza R, Villalobos-Hurtado R, Avalos-Diaz E (1999) Ontogeny of Ro hYRNAs in human heart. Scand J Rheumatol 28:100–105CrossRefPubMedGoogle Scholar
  15. Garcia S, Nascimento JHM, Bonfa E, Levy R, Oliveria SF, Tavares AV, de Carvalho AC (1994) Cellular mechanism of the conduction abnormalities induced by serum from anti-Ro/SSA-positive patients in rabbit hearts. J Clin Invest 93:718–724PubMedGoogle Scholar
  16. George PM, Tunnessen WW Jr (1993) Childhood discoid lupus erythematosus. Arch Dermatol 129:613–617CrossRefPubMedGoogle Scholar
  17. Harmon CE, Lee LA, Huff JC, Norris DA, Weston WL (1984) The frequency of antibodies to the SSA/Ro antigen in pregnancy sera. Arthritis Rheum 28:S20Google Scholar
  18. Ho SY, Esscher E, Anderson RH, Michaëlsson M (1986) Anatomy of congenital complete heart block and relation to maternal anti-Ro antibodies. Am J Cardiol 58:291–294CrossRefPubMedGoogle Scholar
  19. Jewell ML, McCauliffe DP (2000) Patients with cutaneous lupus erythematosus who smoke are less responsive to antimalarial treatment. J Am Acad Dermatol 42:983–987CrossRefPubMedGoogle Scholar
  20. Julkunen H, Kaaja R, Wallgren E, Teramo K (1993) Isolated congenital heart block: fetal and infant outcome and familial incidence of heart block. Obstet Gynecol 82:11–16PubMedGoogle Scholar
  21. Kettler AH, Bean SF, Duffy JO, Gammon WR (1988) Systemic lupus erythematosus presenting as a bullous eruption in a child. Arch Dermatol 124:1083–1087CrossRefPubMedGoogle Scholar
  22. Kuhn A, Richter-Hintz D, Oslislo C, Ruzicka T, Megahed M, Lehmann P (2000) Lupus erythematosus tumidus — a neglected subset of cutaneous lupus erythematosus: report of 40 cases. Arch Dermatol 136:1033–1041PubMedGoogle Scholar
  23. Lawrence S, Luy L, Laxer R, Krafchik B, Silverman E (2000) The health of mothers of children with cutaneous neonatal lupus erythematosus differs from that of mothers of children with congenital heart block. Am J Med 108:705–709CrossRefPubMedGoogle Scholar
  24. Lee LA (1993) Neonatal lupus erythematosus. J Invest Dermatol 100:9S–13SCrossRefPubMedGoogle Scholar
  25. Lee LA (2001) Neonatal lupus: clinical features, therapy, and pathogenesis. Curr Rheumatol Rep 3:391–395PubMedGoogle Scholar
  26. Lee LA, Weston WL (1996) Special considerations concerning the cutaneous manifestations of rheumatic diseases in children. In: Sontheimer RD, Provost TT (eds) Cutaneous manifestations of rheumatic diseases. Williams & Wilkins, Baltimore, pp 323–344Google Scholar
  27. Lee LA, Bias WB, Arnett FC Jr, Huff JC, Norris DA, Harmon C, Provost TT, Weston WL (1983) Immunogenetics of the neonatal lupus syndrome. Ann Intern Med 99:592–596PubMedGoogle Scholar
  28. Lee LA, Weston WL, Krueger GG, Emam M, Reichlin M, Stevens JO, Surbrugg SK, Vasil A, Norris DA (1986) An animal model of antibody binding in cutaneous lupus. Arthritis Rheum 29:782–788PubMedGoogle Scholar
  29. Lee LA, Coulter S, Erner S, Chu H (1987) Cardiac immunoglobulin deposition in congenital heart block associated with maternal anti-Ro autoantibodies. Am J Med 83:793–796CrossRefPubMedGoogle Scholar
  30. Lee LA, Gaither KK, Coulter SN, Norris DA, Harley JB (1989) Pattern of cutaneous immunoglobulin G deposition in subacute cutaneous lupus erythematosus is reproduced by infusing purified anti-Ro (SSA) autoantibodies into human skin-grafted mice. J Clin Invest 83:1556–1562PubMedGoogle Scholar
  31. Lee LA, Reichlin M, Ruyle SZ, Weston WL (1993) Neonatal lupus liver disease. Lupus 2:333–338PubMedGoogle Scholar
  32. Lee LA, Frank MB, McCubbin VR, Reichlin M (1994) The autoantibodies of neonatal lupus erythematosus. J Invest Dermatol 102:963–966CrossRefPubMedGoogle Scholar
  33. Lee LA, Sokol RJ, Buyon JP (2002) Hepatobiliary disease in neonatal lupus: prevalence and clinical characteristics in cases enrolled in a national registry. Pediatrics 109:E11CrossRefPubMedGoogle Scholar
  34. Lehman TJA, Reichlin M, Santner TJ, Silvermann E, Petty RE, Spencer CH, Harley JB (1989) Maternal antibodies to Ro (SS-A) are associated with both early onset of disease and male sex among children with systemic lupus erythematosus. Arthritis Rheum 32:1414–1420PubMedGoogle Scholar
  35. Lehman TJA (1993) Systemic lupus erythematosus in childhood and adolescence. In:Wallace DJ, Hahn BH (eds) Dubois’ lupus erythematosus. Lea & Febiger, Philadelphia, pp 431–441Google Scholar
  36. Lev M, Silverman J, Fitzmaurice FM, Paul MH, Cassels DE, Miller RA (1971) Lack of connection between the atria and the more peripheral conduction system in congenital atrioventricular block. Am J Cardiol 27:481–488CrossRefPubMedGoogle Scholar
  37. Lieu TS, Newkirk MM, Arnett FC, Lee LA, Deng JS, Capro JD, Sontheimer RD (1989) A major autoepitope is presenton the amino terminus of a human SS-A/Ro polypeptide. J Autoimmun 2:367–374PubMedGoogle Scholar
  38. Maddison PJ, Lee L, Reichlin M, Sinclair A, Wasson C, Schemmer G, Reichlin M (1995) Anti-p57: a novel association with neonatal lupus. Clin Exp Immunol 99:42–48PubMedGoogle Scholar
  39. Manzi S, Urbach AH, McCune A, Altman HA, Kaplan SS, Medsger TA Jr, Ramsey-Goldman R (1991) Systemic lupus erythematosus in a boy with chronic granulomatous disease: case report and review of the literature. Arthritis Rheum 34:101–105PubMedGoogle Scholar
  40. Mazel JA, El-Sherif N, Buyon J, Boutjdir M (1999) Electrocardiographic abnormalities in a murine model injected with IgG from mothers of children with congenital heart block. Circulation 99:1914–1918PubMedGoogle Scholar
  41. McCune AB, Weston WL, Lee LA (1987) Maternal and fetal outcome in neonatal lupus erythematosus. Ann Intern Med 106:518–523PubMedGoogle Scholar
  42. Meyer O, Hauptmann G, Tappeiner G, Ochs HD, Mascart-Lemone F (1985) Genetic deficiency of C4, C2 or C1q and lupus syndromes. Association with anti-Ro (SS-A) antibodies. Clin Exp Immunol 62:678–684PubMedGoogle Scholar
  43. Miyagawa S, Yanagi K, Yoshioka A, Kidoguchi K, Shirai T, Hayashi Y (1998) Neonatal lupus erythematosus: maternal IgG antibodies bind to a recombinant NH2-terminal fusion protein encoded by human alpha-fodrin cDNA. J Invest Dermatol 111:1189–1192CrossRefPubMedGoogle Scholar
  44. Miyagawa S, Shinohara K, Kidoguchi K, Fujita T, Fukumoto T, Hashimoto K, Yoshioko A, Shirai T (1997) Neonatal lupus erythematosus: studies on HLA class II genes and autoantibody profiles in Japanese mothers. Autoimmunity 26:95–101PubMedGoogle Scholar
  45. Miyagawa S, Kidoguchi K, Kaneshige T, Shirai T (1999) Neonatal lupus erythematosus: analysis of HLA class I genes in Japanese child/mother pairs. Lupus 8:751–754CrossRefPubMedGoogle Scholar
  46. Neiman AR, Lee LA, Weston WL, Buyon JP (2000) Cutaneous manifestations of neonatal lupus without heart block: Characteristics of mothers and children enrolled in a national registry. J Pediatr 137:674–680CrossRefPubMedGoogle Scholar
  47. Newton RC, Jorizzo JL, Solomon AR Jr, Sanches RL, Daniels JC, Bell JD, Cavallo T (1986) Mechanism-oriented assessment of isotretinoin in chronic or subacute cutaneous lupus erythematosus. Arch Dermatol 122:170–176CrossRefPubMedGoogle Scholar
  48. Press J, Uziel Y, Laxer RM, Luy L, Hamilton RM, Silverman ED (1996) Long-term outcome of mothers of children with complete congenital heart block. Am J Med 100:328–332CrossRefPubMedGoogle Scholar
  49. Provost TT, Arnett FC, Reichlin M (1983) Homozygous C2 deficiency, lupus erythematosus and anti-Ro (SSA) antibodies. Arthritis Rheum 26: 1279–1282PubMedGoogle Scholar
  50. Provost TT, Watson R, Gammon WR, Radowsky M, Harley JB, Reichlin M (1987) The neonatal lupus syndrome associated with U1RNP (nRNP) antibodies. N Engl J Med 31:1135–1138Google Scholar
  51. Qu Y, Xiao GQ, Chen L, Boutjdir M (2001) Autoantibodies from mothers of children with congenital heart block downregulate cardiac L-type Ca channels. J Mol Cell Cardiol 33: 1153–1163CrossRefPubMedGoogle Scholar
  52. Rahman P, Gladman DD, Urowitz MB (1998) Smoking interferes with efficacy of antimalarial therapy in cutaneous lupus. J Rheumatol 25: 1716–1719PubMedGoogle Scholar
  53. Reichlin M, Brucato A, Frank MB, Maddison PJ, McCubbin VR, Wolfson-Reichlin M, Lee LA (1994) Concentration of autoantibodies to native 60 kd Ro/SS-A and denatured 52 kd Ro/SS-A in eluates from the heart of a child who died with congenital complete heart block. Arthritis Rheum 37:1698–1703PubMedGoogle Scholar
  54. Schaller J (1982) Lupus in childhood. Clin Rheum Dis 8:219–228PubMedGoogle Scholar
  55. Shinohara K, Miyagawa S, Fujita T, Aono T, Kidoguchi K (1999) Neonatal lupus erythematosus: results of maternal corticosteroid therapy. Obstet Gynecol 93:952–957CrossRefPubMedGoogle Scholar
  56. Siamopoulou MA, Stefanou D, Drosos AA (1989) Subacute cutaneous lupus-erythematosus in childhood. Clin Rheumatol 8:533–537CrossRefPubMedGoogle Scholar
  57. Siegel M, Lee SL (1973) The epidemiology of systemic lupus erythematosus. Semin Arthritis Rheum 3:1–54CrossRefPubMedGoogle Scholar
  58. Taieb A, Hehunstre JP, Goetz J, Surleve Bazeille JE, Fizet D, Hauptmann G, Maleville J (1986) Lupus erythematosus panniculitis with partial genetic deficiency of C2 and C4 in a child. Arch Dermatol 122:576–582CrossRefPubMedGoogle Scholar
  59. Taylor-Albert E, Reichlin M, Toews WH, Overholt ED, Lee LA (1997) Delayed dilated cardiomyopathy as a manifestation of neonatal lupus: case reports, autoantibod yanalysis, and management. Pediatrics 99:733–735CrossRefPubMedGoogle Scholar
  60. Thornton CM, Eichenfield LF, Shinall EA, Siegfried E, Rabinowitz LG, Esterly NB, Lucky AW, Friedlander SF (1995) Cutaneous telangiectases in neonatal lupus erythematosus. J Am Acad Dermatol 33:19–25CrossRefPubMedGoogle Scholar
  61. Viana VS, Garcia S, Nascimento JH, Elkon KB, Brot N, Campos de Carvalho AC, Bonfa E (1998) Induction of in vitro heart block is not restricted to affinity purified anti-52kDa Ro/SSA antibody from mothers of children with neonatal lupus. Lupus 7:141–147CrossRefPubMedGoogle Scholar
  62. Vlachoyiannopoulos PG, Karassa FB, Karakostas KX, Drosos AA, Moutsopoulos HM (1993) Systemic lupus erythematosus in Greece. Clinical features, evolution and outcome: a descriptive analysis of 292 patients. Lupus 2:303–312PubMedGoogle Scholar
  63. Waltuck J, Buyon JP (1994) Autoantibody-associated congenital heart block: outcome in mothers and children. Ann Intern Med 120:544–551PubMedGoogle Scholar
  64. Wananukul S, Watana D, Pongprasit P (1998) Cutaneous manifestations of childhood systemic lupus erythematosus. Pediatr Dermatol 15:342–346CrossRefPubMedGoogle Scholar
  65. Wang D, Buyon JP, Zhu W, Chan EK (1999) Defining a novel 75-kDa phosphoprotein associated with SS-A/Roand identification of distincthuman autoantibodies. J Clin Invest 104:1265–1275PubMedGoogle Scholar
  66. Watson RM, Scheel JN, Petri M, Lee LA, Bias WB, McLean RH (1992) Neonatal lupus erythematosus syndrome: analysis of C4 allotypes and C4 genes in 18 families. Medicine 71:84–95PubMedGoogle Scholar
  67. Watson R, Kang JE, May M, Hudak M, Kickler T, Provost TT (1988) Thrombocytopenia in the neonatal lupus syndrome. Arch Dermatol 124:560–563CrossRefPubMedGoogle Scholar
  68. Weston WL, Harmon C, Peebles C, Manchester D, Franco HL, Huff JC, Norris DA (1982) A serological marker for neonatal lupus erythematosus. Br J Dermatol 107:377–382PubMedGoogle Scholar
  69. Weston WL, Morelli JG, Lee LA (1999) The clinical spectrum of anti-Ro-positive cutaneous neonatal lupus erythematosus. J Am Acad Dermatol 40:675–681PubMedGoogle Scholar
  70. Yamada H, Kato EH, Ebina Y, Moriwaki M, Yamamoto R, Furuta J, Fujimoto S (1999) Fetal treatment of congenital heart block ascribed to anti-SSA antibody: case reports with observation of cardiohemodynamics and review of the literature. Am J Reprod Immunol 42:226–232PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 2005

Authors and Affiliations

  • Lela A. Lee

There are no affiliations available

Personalised recommendations