Advertisement

Autoimmune Blistering Diseases in Children

  • Amy TheosEmail author
Chapter

Abstract

The acquired autoimmune bullous diseases are rare in children, but early recognition and prompt treatment are important. A high index of suspicion is necessary to diagnose these conditions that frequently mimic more common childhood diseases. Because there is clinical and histological overlap between these groups of diseases, direct immunofluorescence and/or indirect immunofluorescence are necessary for diagnostic confirmation. The quality of published data regarding the treatment of autoimmune bullous diseases in children is poor, as there are no controlled or comparative trials. This makes it difficult to draw conclusions regarding the best treatment algorithms. Nevertheless, numerous case reports and small, mostly retrospective, case series do suggest treatment options. The goal of treatment is to suppress disease activity and control symptoms with therapies that minimize the potential for serious short and long term adverse effects. Since children may be especially vulnerable to certain medication side effects (e.g., growth retardation from corticosteroids), this makes choosing the best treatment even more important. This chapter will review the most common autoimmune bullous diseases occurring in children: chronic bullous disease of childhood, dermatitis herpetiformis, bullous pemphigoid, epidermolysis bullosa acquisita, and pemphigus.

Keywords

Chronic bullous disease of childhood Linear IgA disease of childhood Dermatitis herpetiformis Bullous pemphigoid Epidermolysis bullosa acquisita Pemphigus vulgaris Pemphigus foliaceus Neonatal pemphigus Juvenile Adolescent Child Treatment 

Abbreviations

BMZ

Basement membrane zone

BP

Bullous pemphigoid

C3

Complement 3

CBC

Complete blood count

CBDC

Chronic bullous disease of childhood

DH

Dermatitis herpetiformis

DIF

Direct immunofluorescence

DPT

Diphtheria pertussis, and tetanus vaccination

EBA

Epidermolysis bullosa acquisita

ELISA

Enzyme-linked immunosorbent assay

FDA

Federal Drug Administration

G6PD

Glucose-6-phosphate dehydrogenase

IgA

Immunoglobulin A

IgG

Immunoglobulin G

IgM

Immunoglobulin M

IIF

Indirect immunofluorescence

IVIG

Intravenous immunoglobulin

PF

Pemphigus foliaceus

PNP

Paraneoplastic pemphigus

PV

Pemphigus vulgaris

TPMT

Thiopurine methyl transferase

References

  1. 1.
    Wojnarowska F, Marsden RA, Bhogal B, Black MM. Chronic bullous disease of childhood, childhood cicatricial pemphigoid, and linear IgA disease of adults. A comparative study demonstrating clinical and immunopathologic overlap. J Am Acad Dermatol. 1988;19:792–805.CrossRefPubMedGoogle Scholar
  2. 2.
    Burge S, Wojnarowska F, Marsden A. Chronic bullous dermatosis of childhood persisting into adulthood. Pediatr Dermatol. 1988;5:246–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Monia K, Aida K, Amel K, et al. Linear IgA bullous dermatosis in Tunisian children: 31 cases. Indian J Dermatol. 2011;56:153–9.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Edwards S, Wojnarowska F, Armstrong LM. Chronic bullous disease of childhood with oral mucosal scarring. Clin Exp Dermatol. 1991;16:41–3.CrossRefPubMedGoogle Scholar
  5. 5.
    Simon JC, Dietrich A, Kapp A, Schopf E. Chronic bullous dermatosis in childhood. Association with salmonella enteritis. Hautarzt. 1995;46:485–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Baldari U, Raccagni AA, Celli B, Righini MG. Chronic bullous disease of childhood following Epstein-Barr virus seroconversion: a case report. Clin Exp Dermatol. 1996;21:123–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Nanda A, Dvorak R, Al-Sabah H, Alsaleh QA. Linear IgA bullous disease of childhood: an experience from Kuwait. Pediatr Dermatol. 2006;23:443–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Ho JC, Ng PL, Tan SH, Giam YC. Childhood linear IgA bullous disease triggered by amoxicillin-clavulanic acid. Pediatr Dermatol. 2007;24:E40–3.CrossRefPubMedGoogle Scholar
  9. 9.
    Nantel-Battista M, Al Dhaybi R, Hatami A, et al. Childhood linear IgA bullous disease induced by trimethoprim-sulfamethoxazole. J Dermatol Case Rep. 2010;3:33–5.Google Scholar
  10. 10.
    Kenani N, Mebazaa A, Denguezli M, et al. Childhood linear IgA bullous dermatosis in Tunisia. Pediatr Dermatol. 2009;26:28–33.CrossRefPubMedGoogle Scholar
  11. 11.
    Chorzelski TP, Jablonska S. IgA linear dermatosis of childhood (chronic bullous disease of childhood). Br J Dermatol. 1979;101:535–42.CrossRefPubMedGoogle Scholar
  12. 12.
    Prystowsky S, Gilliam JN. Benign chronic bullous dermatosis of childhood. Linear IgA and C3 deposition on the basement membrane. Arch Dermatol. 1976;112:837–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Powell J, Kirtschig G, Allen J, et al. Mixed immunobullous disease of childhood: a good response to antimicrobials. Br J Dermatol. 2001;144:769–74.CrossRefPubMedGoogle Scholar
  14. 14.
    Willsteed E, Bhogal BS, Black MM, et al. Use of 1 M NaCl split skin in the indirect immunofluorescence of the linear IgA bullous dermatoses. J Cutan Pathol. 1990;17:144–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Marsden RA, McKee PH, Bhogal B, et al. A study of benign chronic bullous dermatosis of childhood and comparison with dermatitis herpetiformis and bullous pemphigoid occurring in childhood. Clin Exp Dermatol. 1980;5:159–76.CrossRefPubMedGoogle Scholar
  16. 16.
    Rogers M, Bartlett B, Walder B, Cains G. Chronic bullous disease of childhood –aspects of management. Aust J Derm. 1982;23:62–9.CrossRefGoogle Scholar
  17. 17.
    Marsden RA. The treatment of benign chronic bullous dermatosis of childhood, and dermatitis herpetiformis and bullous pemphigoid beginning I childhood. Clin Exp Dermatol. 1982;7:653–63.CrossRefPubMedGoogle Scholar
  18. 18.
    Ang P, Goh BK, Giam YC. Case reports of linear IgA bullous dermatosis of childhood. Ann Acad Singapore. 1999;28:849–54.Google Scholar
  19. 19.
    Alajlan A, Al-Khawajah M, Al-Sheikh O, et al. Treatment of linear IgA bullous dermatosis of childhood with flucloxacillin. J Am Acad Dermatol. 2006;54:652–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Siegfried EC, Sirawan S. Chronic bullous disease of childhood: successful treatment with dicloxacillin. J Am Acad Dermatol. 1998;39:797–800.CrossRefPubMedGoogle Scholar
  21. 21.
    de las Heras MN. Linear IgA bullous dermatosis of childhood: good response to antibiotic treatment. Clin Exp Dermatol. 2014;39:395–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Skinner Jr RB, Rotondo CK, Schneider MA, et al. Treatment of chronic bullous dermatosis of childhood with oral dicloxacillin. Pediatr Dermatol. 1995;12:65–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Cooper SM, Powell J, Wojnarowska F. Linear IgA disease: successful treatment with erythromycin. Clin Exp Dermatol. 2002;27:677–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Farrant P, Carley C, Carmichael A. Is erythromycin an effective treatment for chronic bullous disease of childhood? A national survey of members of the British Society for Paediatric Dermatology. Pediatr Dermatol. 2008;25:479–82.CrossRefPubMedGoogle Scholar
  25. 25.
    Piamphongsant T, Sirimachan S, Himmunknan P. Juvenile blistering diseases: the problems of diagnosis and treatment. Asian Pac J Allergy Immunol. 1986;4:133–7.PubMedGoogle Scholar
  26. 26.
    Pulimood S, Ajithkumar K, Jacob M, et al. Linear IgA bullous dermatosis of childhood: treatment with dapsone and co-trimoxazole. Clin Exp Dermatol. 1997;22:90–1.CrossRefPubMedGoogle Scholar
  27. 27.
    Banodkar DD, Al-Suwaid AR. Colchicine as a novel therapeutic agent in chronic bullous dermatosis of childhood. Int J Dermatol. 1997;36:213–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Ang P, Tay YK. Treatment of linear IgA bullous dermatosis of childhood with colchicine. Pediatr Dermatol. 1999;16:50–2.CrossRefPubMedGoogle Scholar
  29. 29.
    Zeharia A, Hodak E, Mukamel M, et al. Successful treatment of chronic bullous dermatosis of childhood wit colchicine. J Am Acad Dermatol. 1994;30:660–1.CrossRefPubMedGoogle Scholar
  30. 30.
    Nousari HC, Sragovich A, Kimyai-Asadi A, et al. Mycophenolate mofetil in autoimmune and inflammatory skin disorders. J Am Acad Dermatol. 1999;40:265–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Farley-Li J, Mancini AJ. Treatment of linear IgA bullous dermatosis of childhood with mycophenolate mofetil. Arch Dermatol. 2003;139:1121–4.CrossRefPubMedGoogle Scholar
  32. 32.
    Khanna N, Pandhi RK, Gupta S, Singh MK. Response of chronic bullous dermatosis of childhood to a combination of dapsone and nicotinamide. J Eur Acad Dermatol Venereol. 2001;15:368.PubMedGoogle Scholar
  33. 33.
    Dauendorffer JN, Mahe E, Saiag P. Tacrolimus ointment, an interesting adjunctive therapy for childhood linear IgA bullous dermatosis. J Eur Acad Dermatol Venereol. 2008;22:364–5.CrossRefPubMedGoogle Scholar
  34. 34.
    Madnani NA, Khan KJ. Linear IgA bullous dermatosis of childhood: response to thalidomide. Indian J Dermatol Venereol Leprol. 2010;76:427–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Moleiro S, Santos V, Calha M, Pessoa G. Atypical response to treatment in linear IgA bullous dermatosis of childhood: Revision of literature. Dermatol Online J. 2011;17:5.PubMedGoogle Scholar
  36. 36.
    Mintz EM, Morel KD. Treatment of chronic bullous disease of childhood. Dermatol Clin. 2011;29:699–700.CrossRefPubMedGoogle Scholar
  37. 37.
    Esterly NB, Furey NL, Kirschner BS, et al. Chronic bullous dermatosis of childhood. Arch Dermatol. 1977;113:42–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Lemberg D, Day AS, Bohane T. Coeliac disease presenting as dermatitis herpetiformis in infancy. J Paediatri Child Health. 2005;41:294–6.CrossRefGoogle Scholar
  39. 39.
    Sansaricq F, Stein SL, Petronic-Rosic V. Autoimmune bullous diseases in childhood. Clin Dermatol. 2012;30:114–27.CrossRefPubMedGoogle Scholar
  40. 40.
    Heinlin J, Knoppke B, Kohl E, et al. Dermatitis herpetiformis presenting as digital petechiae. Pediatri Dermatol. 2012;29:209–12.CrossRefGoogle Scholar
  41. 41.
    Ermacora E, Prampolini L, Tribbia G, et al. Long-term follow-up of dermatitis herpetiformis in children. J Am Acad Dermatol. 1986;15:24–30.CrossRefPubMedGoogle Scholar
  42. 42.
    Willsteed E, Lee M, Wong LC, Cooper A. Sulfasalazine and dermatitis herpetiformis. Australas J Dermatol. 2005;46:101–3.CrossRefPubMedGoogle Scholar
  43. 43.
    Lowney ED. Use of sulfasalazine in dermatitis herpetiformis in young people. Arch Dermatol. 1978;114:1553.CrossRefPubMedGoogle Scholar
  44. 44.
    Fisler RE, Saeb M, Liang MG, et al. Childhood bullous pemphigoid. A clinicopathologic study and review of the literature. Am J Dermatopathol. 2003;25:183–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Waisbourd-Zinman O, Ben-Amitai D, Cohen A, et al. Bullous pemphigoid in infancy: clinical and epidemiologic characteristics. J Am Acad Dermatol. 2008;58:41–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Schumann H, Amann U, Tasanen K, et al. A child with localized vulval pemphigoid and IgG autoantibodies targeting the C-terminus of collagen XVII/BP180. Br J Dermatol. 1999;140:1133–8.CrossRefPubMedGoogle Scholar
  47. 47.
    Saad RW, Domloge-Hultsch N, Yancey KB, et al. Childhood localized vulvar pemphigoid is a true variant of bullous pemphigoid. Arch Dermatol. 1992;128:807–10.CrossRefPubMedGoogle Scholar
  48. 48.
    Kuenzli S, Grimaitre M, Irischer J, et al. Childhood bullous pemphigoid: report of a case with life-threatening course during homeopathy treatment. Pediatr Dermatol. 2004;21:160–3.CrossRefPubMedGoogle Scholar
  49. 49.
    Trueb RM, Didierjean L, Fellas A, et al. Childhood bullous pemphigoid: report of a case with characterization of the targeted antigens. J Am Acad Dermatol. 1999;40:338–44.CrossRefPubMedGoogle Scholar
  50. 50.
    de la Fuente S, Hernandez-Martin A, de Lucas R, et al. Postvaccination bullous pemphigoid in infancy: report of three new cases and literature review. Pediatr Dermatol. 2013;30:741–4.CrossRefPubMedGoogle Scholar
  51. 51.
    Oranje AP, van Joost T. Pemphigoid in children. Pediatr Dermatol. 1989;6:267–74.CrossRefPubMedGoogle Scholar
  52. 52.
    Nemeth AJ, Klein AD, Gould EW, Schachner LA. Childhood bullous pemphigoid. Arch Dermatol. 1991;127:378–86.CrossRefPubMedGoogle Scholar
  53. 53.
    Edwards S, Wakelin SH, Wojnarowska F, et al. Bullous pemphigoid and epidermolysis bullosa acquisita: presentation, prognosis, and immunopathology in 11 children. Pediatr Dermatol. 1998;15:184–90.CrossRefPubMedGoogle Scholar
  54. 54.
    Marcus KA, Halbertsma FJ, van Steensel MA. A case of juvenile bullous pemphigoid – successful treatment with diaminodiphenylsulfone and prednisone. Pediatr Dermatol. 2009;26:55–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Osawa M, Ueda-Hayakawa I, Isei T, et al. A case of childhood bullous pemphigoid with IgG and IgA autoantibodies to various domains of BP180. J Am Acad Dermatol. 2014;70:129–31.CrossRefGoogle Scholar
  56. 56.
    Motegi S, Abe M, Tamura A, et al. Childhood bullous pemphigoid successfully treated with diaminodiphenyl sulfone. J Dermatol. 2005;32:809–12.CrossRefPubMedGoogle Scholar
  57. 57.
    Petronius D, Bergman R. Bullous pemphigoid in two young infants. Pediatr Dermatol. 2002;19:119–21.CrossRefPubMedGoogle Scholar
  58. 58.
    Chimanovitch I, Hamm H, Georgi M, et al. Bullous pemphigoid of childhood: autoantibodies target the same epitopes within the NC16A domain of BP180 as autoantibodies in bullous pemphigoid of adulthood. Arch Dermatol. 2000;136:527–32.CrossRefPubMedGoogle Scholar
  59. 59.
    Oranje AP, Vuzevski VD, van Joost T, et al. Bullous pemphigoid in children. Report of three cases with special emphasis on therapy. Int J Dermatol. 1991;30:339–42.CrossRefPubMedGoogle Scholar
  60. 60.
    Fox JC, Kenkare S, Petronic-Rosic V, et al. Bullous pemphigoid in late childhood successfully treated with mycophenolate mofetil as an adjuvant therapy. Pediatr Dermatol. 2010;27:537–9.CrossRefPubMedGoogle Scholar
  61. 61.
    Xiao T, Li B, Wang YK, et al. Childhood bullous pemphigoid treated by i.v. Immunoglobulin. J Dermatol. 2007;34:650–3.CrossRefPubMedGoogle Scholar
  62. 62.
    Ister M, Pouessel G, Ythier H, et al. Postvaccinal, corticosteroid-resistant bullous pemphigoid in infancy: treatment with intravenous immunoglobulin. Pediatr Dermatol. 2014;31:e94–5.CrossRefPubMedGoogle Scholar
  63. 63.
    Fuertes I, Luelmo J, Leal L, et al. Refractory childhood pemphigoid successfully treated with rituximab. Pediatr Dermatol. 2013;30:e96–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Schulze J, Bader P, Henke U, et al. Severe bullous pemphigoid in an infant—successful treatment with rituximab. Pediatr Dermatol. 2008;25:462–5.CrossRefPubMedGoogle Scholar
  65. 65.
    Szabolcs P, Reese M, Yancey KB, et al. Combination treatment of bullous pemphigoid with anti-CD20 and anti-CD25 antibodies in a patient with chronic graft-versus-host disease. Bone Marrow Transplant. 2002;30:327–9.CrossRefPubMedGoogle Scholar
  66. 66.
    Schmidt E, Seitz CS, Benoit S, et al. Rituximab in autoimmune bullous diseases: mixed responses and adverse effects. Br J Dermatol. 2007;156:352–6.CrossRefPubMedGoogle Scholar
  67. 67.
    Fox BJ, Odom RB, Findlay RF. Erythromycin therapy in bullous pemphigoid: possible anti-inflammatory effects. J Am Acad Dermatol. 1982;7:504–10.CrossRefPubMedGoogle Scholar
  68. 68.
    Lebeau S, Mainetti C, Masouye I, et al. Localized childhood vulval pemphigoid treated with tacrolimus ointment. Dermatology. 2004;208:273–5.CrossRefPubMedGoogle Scholar
  69. 69.
    Tripodi G, Risso M, Tenerini L, et al. Drug-resistant bullous pemphigoid and inflammatory bowel disease in a pediatric case successfully treated by plasma exchange and extracorporeal photochemotherapy. J Clin Apher. 2007;22:26–30.CrossRefPubMedGoogle Scholar
  70. 70.
    Mayuzumi M, Akiyama M, Nishie W, et al. Childhood epidermolysis bullosa acquisita with autoantibodies against the noncollagenous 1 and 2 domains of type VII collagen: case report and review of the literature. Br J Dermatol. 2006;155:1048–52.CrossRefPubMedGoogle Scholar
  71. 71.
    Baican A, Chiriac G, Torio-Padron N, Sitaru C. Childhood epidermolysis bullosa acquisita associated with severe dental alterations: a case presentation. J Dermatol. 2013;40:410–1.CrossRefPubMedGoogle Scholar
  72. 72.
    Yang B, Wang C, Wang N, et al. Childhood epidermolysis bullosa acquisita: report of a Chinese case. Pediatr Dermatol. 2012;29:614–7.CrossRefPubMedGoogle Scholar
  73. 73.
    Abrams ML, Smidt A, Benjamin L, et al. Congenital epidermolysis bullosa acquisita: vertical transfer of maternal autoantibody from mother to infant. Arch Dermatol. 2011;147:337–41.CrossRefPubMedGoogle Scholar
  74. 74.
    Tran MM, Anhalt GJ, Barrett T, Cohen BA. Childhood IgA-mediated epidermolysis bullosa responding to mycophenolate mofetil as a corticosteroid-sparing agent. J Am Acad Dermatol. 2006;54:734–6.CrossRefPubMedGoogle Scholar
  75. 75.
    Schmidt E, Hopfner B, Chen M, et al. Childhood epidermolysis bullosa acquisita: a novel variant with reactivity to all three structural domains of type VII collagen. Br J Dermatol. 2002;147:592–7.CrossRefPubMedGoogle Scholar
  76. 76.
    Trigo-Guzman FX, Conti A, Aoki V, et al. Epidermolysis bullosa acquisita in childhood. J Dermatol. 2003;30:226–9.CrossRefPubMedGoogle Scholar
  77. 77.
    Su JC, Varigos GA, Dowling J. Epidermolysis bullosa acquisita in childhood. Australas J Dermatol. 1998;39:38–41.CrossRefPubMedGoogle Scholar
  78. 78.
    Callot-Mellot C, Bodemer C, Caux F, et al. Epidermolysis bullosa acquisita in childhood. Arch Dermatol. 1997;133:1122–6.CrossRefPubMedGoogle Scholar
  79. 79.
    Park SB, Cho KH, Youn JL, et al. Epidermolysis bullosa acquisita in childhood—a case mimicking chronic bullous dermatosis of childhood. Clin Exp Dermatol. 1997;22:220–2.CrossRefPubMedGoogle Scholar
  80. 80.
    Caux F, Kirtschig G, Lemarchand-Venencie F, et al. IgA-epidermolysis bullosa acquisita in a child resulting in blindness. Br J Dermatol. 1997;137:270–5.CrossRefPubMedGoogle Scholar
  81. 81.
    Bjarnason B, Flosadottir E. Childhood, neonatal, and stillborn pemphigus vulgaris. Int J Dermatol. 1999;38:680–8.CrossRefPubMedGoogle Scholar
  82. 82.
    Popadic S, Medenica L, Skiljevic D, et al. Pemphigus vulgaris in three adolescents: The course of the disease. Australas J Dermatol. 2011;52:e3–7.CrossRefPubMedGoogle Scholar
  83. 83.
    Asarch A, Gurcan HM, Ahmed AR. A current review of juvenile pemphigus vulgaris: analysis of data on clinical outcomes. Am J Clin Dermatol. 2010;11:21–33.CrossRefPubMedGoogle Scholar
  84. 84.
    Metry DW, Hebert AA, Jordon RE. Nonendemic pemphigus foliaceus in children. J Am Acad Dermatol. 2002;46:419–22.CrossRefPubMedGoogle Scholar
  85. 85.
    Mimouni D, Anhalt GJ, Lazarova Z, et al. Paraneoplastic pemphigus in children and adolescents. Br J Dermatol. 2002;147:725–32.CrossRefPubMedGoogle Scholar
  86. 86.
    Mabrouk D, Ahmed R. Analysis of current therapy and clinical outcome in childhood pemphigus vulgaris. Pediatr Dermatol. 2011;28:485–93.CrossRefPubMedGoogle Scholar
  87. 87.
    Asarch A, Ahmed AR. Treatment of juvenile pemphigus vulgaris with intravenous immunoglobulin therapy. Pediatr Dermatol. 2009;26:197–202.CrossRefPubMedGoogle Scholar
  88. 88.
    Vinay K, Kanwar AJ, Sawatkar GU, et al. Successful use of rituximab in the treatment of childhood and juvenile pemphigus. J Am Acad Dermatol. 2014;71:669–75.CrossRefPubMedGoogle Scholar
  89. 89.
    Fuertes I, Guilabert A, Mascaro JM, Iranzo P. Rituximab in childhood pemphigus vulgaris: a long-term follow-up case and review of the literature. Dermatology. 2010;22:13–6.CrossRefGoogle Scholar
  90. 90.
    Petratos MA, Andrade R. Pemphigus erythematosus. Report of a case in a child less than 6 year of age. Am J Dis Child. 1967;113:394–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of DermatologyUniversity of Alabama at BirminghamBirminghamUSA

Personalised recommendations