Subepidermal Bullous Dermatoses

  • Mirian Nacagami SottoEmail author
  • Mai P. Hoang


The autoimmune bullous dermatoses discussed in this chapter are the consequence of defects at or near the basement membrane zone. At the light microscopy level, the subepidermal bullous dermatoses can generally be classified based upon the predominant type of inflammatory cells within the blister space: cell-poor, eosinophils, neutrophils, or lymphocytes. The pauci-inflammatory group includes epidermolysis bullosa (EB) and porphyria cutanea tarda. Using transmission electron microscopy, EB are further classified into four major types (EB simplex, junctional EB, dystrophic EB, and Kindler syndrome) according to the plane of the cleavage. Entities with predominance of eosinophils within the blister space include bullous pemphigoid, mucous membrane pemphigoid/cicatricial pemphigoid, and pemphigoid gestationis. Those containing mainly neutrophils are linear IgA disease, anti-laminin gamma-1 pemphigoid, epidermolysis bullosa acquisita, bullous lupus erythematosus, and dermatitis herpetiformis. Lymphocytes are prominent in lichen planus pemphigoid. Due to overlapping histologic features, direct immunofluorescence (DIF) studies are necessary to distinguish various entities. Of those with similar DIF findings, indirect immunofluorescence (IIF) studies performed on sodium chloride split skin are essential to determine the location of the antigens. In the setting of similar IIF findings as noted in EBA and anti-laminin gamma-1 pemphigoid, immunoblot is needed to confirm the diagnosis.


Bullous dermatosis Subepidermal bullous dermatosis Pemphigoid Epidermolysis bullosa Porphyria cutanea tarda Linear IgA Dermatitis herpetiformis 


  1. 1.
    Fine JD. Inherited epidermolysis bullosa. Orphanet J Rare Dis. 2010;5:12. Scholar
  2. 2.
    Has C, Nystrom A, Saeidian AH, Bruckner-Tuderman L, Uitto J. Epidermolysis bullosa: molecular pathology of connective tissue components in the cutaneous basement membrane zone. Matrix Biol. 2018;71–72:313–329.Google Scholar
  3. 3.
    Fine JD, Bruckner-Tuderman L, Eady RAJ, Bauer EA, Bauer JW, et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70(6):1103–26.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Laimer M, Prodinger C, Bauer JW. Hereditary epidermolysis bullosa. J Dtsch Dermatol Ges. 2015;13(11):1125–33.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Uitto J, Has C, Vahidnezhad H, Youssefian L, Bruckner-Tuderman L. Molecular pathology of the basement membrane zone in heritable blistering diseases: the paradigm of epidermolysis bullosa. Matrix Biol. 2017;57–58:76–85.Google Scholar
  6. 6.
    Küttner V, Mack C, Rigbolt KT, et al. Global remodelling of cellular microenvironment due to loss of collagen VII. Mol Syst Biol. 2013;9:657. Scholar
  7. 7.
    Has C, Castiglia D, del Rio M, et al. Kindler syndrome: extension of FERMT1 mutational spectrum and natural history. Hum Mutat. 2011;32(11):1204–12.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bauer JW, Schaeppi H, Kaserer C, Hantich B, Hintner H. Large melanocytic nevi in hereditary epidermolysis bullosa. J Am Acad Dermatol. 2001;44(4):577–84.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Lanschuetzer CM, Laimer M, Nischler E, Hintner H. Epidermolysis bullosa nevi. Dermatol Clin. 2010;28(1):179–83.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Melo JN, Teruya PY, Machado MC, Valente NS, Sotto MN, Oliveira ZN. Epidermolysis bullosa nevi: clinical, dermatoscopical and histological features in a case of recessive dystrophic form. An Bras Dermatol. 2011;86(4):743–6.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Hintner H, Stingl G, Schuler G, Fritsch P, Stanley J, Katz S, Wolff K. Immunofluorescence mapping of antigenic determinants within the dermal epidermal junction in mechanobullous diseases. J Invest Dermatol. 1981;76(2):113–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Singal AK. Porphyria cutanea tarda: recent update. Mol Genet Metab. 2019. pii: S1096-7192(18)30579-1.Google Scholar
  13. 13.
    Bygum A, Brandrup F. Iron overload in porphyria cutanea tarda. Br J Dermatol. 2000;143(5):1116.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Miura K, Taura K, Kodama K, et al. Hepatitis C virus-induced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity. Hepatology. 2008;8(5):1420–9.CrossRefGoogle Scholar
  15. 15.
    Schulenburg-Brand D, Katugampola R, Anstey AV, Badminton MN. The cutaneous porphyrias. Dermatol Clin. 2014;32(3):369–84.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wissel SP, Sordillo P, Anderson KE, Sassa S, Savillo RL, Kappas A. Porphyria cutanea tarda associated with the acquired immune deficiency syndrome. Am J Hematol. 1987;25(1):107–13.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Aguilera P, Laguno M, To-Figueras J. Human immunodeficiency virus and risk of porphyria cutanea tarda: a possible association examined in a large hospital. Photodermatol Photoimmunol Photomed. 2016;32(2):93–7.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Becker FT. Porphyria cutanea tarda induced by estrogens. Arch Dermatol. 1965;92:252–6.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Horner ME, Alikhan A, Tintle S, Tortorelli S, Davis DM, Hand JL. Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Int J Dermatol. 2013;52(12):1464–80.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zaborowski AG, Paulson GH, Peters AL. Sight threatening complications in porphyria cutanea tarda. Eye (Lond). 2004;18(9):949–50.CrossRefGoogle Scholar
  21. 21.
    Lambrecht RW, Thapar M, Bonkovsky HL. Genetic aspects of porphyria cutanea tarda. Semin Liver Dis. 2007;27(1):99–108.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Fevang SA, Kroon S, Skadberg O. Pseudoporphyria or porphyria cutanea tarda? Diagnostic and treatment difficulties. Acta Derm Venereol. 2008;88(4):426–7.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Amber KT, Murrell DF, Schmidt E, Joly P, Borradori L. Autoimmune subepidermal bullous diseases of the skin and mucosae: clinical features, diagnosis, and management. Clin Rev Allergy Immunol. 2018;54(1):26–51.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Schmidt E, Zillikens D. Pemphigoid diseases. Lancet. 2013;381(9863):320–32.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Zakka LR, Reche P, Ahmed AR. Role of MHC class II genes in the pathogenesis of pemphigoid. Autoimmun Rev. 2011;11(1):40–7.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Arechalde A, Braun RP, Calza AM, Hertl M, Didierjean L, Saurat JH, Borradori L. Childhood bullous pemphigoid associated with IgA antibodies against BP180 or BP230 antigens. Br J Dermatol. 1999;140(1):112–8.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lamberts A, Meijer JM, Jonkman MF. Nonbullous pemphigoid: a systematic review. J Am Acad Dermatol. 2018;78(5):989–95.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Pietkiewicz P, Gornowicz-Porowska J, Bowszyc-Dmochowska M, Bartkiewicz P, Dmochowski M. Bullous pemphigoid and neurodegenerative diseases: a study in a setting of a central European university dermatology department. Aging Clin Exp Res. 2016;28(4):659–63.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Cugno M, Marzano AV, Bucciarelli P, Balice Y, Cianchini G, et al. Increased risk of venous thromboembolism in patients with bullous pemphigoid. The INVENTEP (INcidence of VENous ThromboEmbolism in bullous pemphigoid) study. Thromb Haemost. 2016;115(1):193–9.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Phoon YW, Fook-Chong SM, Koh HY, Thirumoorthy T, Pang SM, Lee HY. Infectious complications in bullous pemphigoid: an analysis of risk factors. J Am Acad Dermatol. 2015;72(5):834–9.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Hodge BD, Roach J, Reserva JL, Patel T, Googe A, Schulmeier J, Brodell RT. The spectrum of histopathologic findings in pemphigoid: avoiding diagnostic pitfalls. J Cutan Pathol. 2018;45(11):831–8.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lehman JS, Carnilleri MJ. Diagnostic utility of direct immunofluorescence findings around hair follicles and sweat glands in immunobullous disease. J Cutan Pathol. 2013;40(2):230–5.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Villani AP, Chouvet B, Kanitakis J. Application of C4d immunohistochemistry on routinely processed tissue sections for the diagnosis of autoimmune bullous dermatoses. Am J Dermatopathol. 2016;38(3):186–8.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Pfaltz K, Mertz K, Rose C, Scheidegger P, Pfaltz M, Kempf W. C3d immunohistochemistry on formalin-fixed tissue is a valuable tool in the diagnosis of bullous pemphigoid of the skin. J Cutan Pathol. 2010;37(6):654–8.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Cizenski JD, Michel P, Watson IT, Frieder J, Wilder EG, Wright JM, Menter MA. Spectrum of orocutaneous disease associations. Immune-mediated conditions. J Am Acad Dermatol. 2017;77(5):795–806.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Leverkus M, Bhol K, Hirako Y, Pas H, Sitaru C, Baier G, et al. Cicatricial pemphigoid with circulating autoantibodies to beta4 integrin, bullous pemphigoid 180 and bullous pemphigoid 230. Br J Dermatol. 2001;145(6):998–1004.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Rose C, Schmidt E, Kerstan A, Thoma-Uszynski S, Wesselmann U, Käsbohrer U, Zillikens D, Shimanovich I. Histopathology of anti-laminin 5 mucous membrane pemphigoid. J Am Acad Dermatol. 2009;61(3):433–40.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Xu HH, Werth VP, Parisi E, Sollecito TP. Mucous membrane pemphigoid. Dent Clin N Am. 2013;57(4):611–30.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Rashid KA, Gurcan HM, Ahmed AR. Antigen specificity in subsets of mucous membrane pemphigoid. J Invest Dermatol. 2006;126(12):2631–6.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Egan CA, Lazarova Z, Darling TN, et al. Anti-epiligrin cicatricial pemphigoid and relative risk for cancer. Lancet. 2001;357(9271):1850–1.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Setterfield J, Shirlaw PJ, Kerr-Muir M, et al. Mucous membrane pemphigoid: a dual circulating antibody response with IgG and IgA signified a more severe and persistent disease. Br J Dermatol. 1998;138(4):602–10.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Vassileva S, Drenovska K, Manuelyan K. Autoimmune blistering dermatoses as systemic diseases. Clin Dermatol. 2014;32(3):364–75.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Daito J, Katoh N, Asai J, et al. Brunsting-Perry cicatricial pemphigoid associated with autoantibodies to the C-terminal domain of BP180. Br J Dermatol. 2008;159(4):984–6.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Mehra T, Guenova E, Dechent F, et al. Diagnostic relevance of direct immunofluorescence in ocular mucous membrane pemphigoid. J Dtsch Dermatol Ges. 2015;13(12):1268–74.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Maderal AD, Lee Salisbury P 3rd, Jorizzo JL. Desquamative gingivitis: diagnosis and treatment. J Am Acad Dermatol. 2018;78(5):851–61.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Lipozencic J, Ljubojevic S, Bukvic-Mokos Z. Pemphigoid gestationis. Clin Dermatol. 2012;30(1):51–5.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Semkova K, Black M. Pemphigoid gestationis: current insights into pathogenesis and treatment. Eur J Obstet Gynecol Reprod Biol. 2009;145(2):138–44.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Kridin K. Subepidermal autoimmune bullous diseases: overview, epidemiology, and associations. Immunol Res. 2018;66(1):6–17.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Kwon EJ, Ntiamoah P, Shulman KJ. The utility of C4d immunohistochemistry on formalin-fixed paraffin-embedded tissue in the distinction of polymorphic eruption of pregnancy from pemphigoid gestationis. Am J Dermatopathol. 2013;35(8):787–91.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Sävervall C, Sand FL, Thomsen SF. Pemphigoid gestationis: current perspectives. Clin Cosmet Investig Dermatol. 2017;10:441–9.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol. 2012;30(1):38–50.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Tsuchisaka A, Ohara K, Ishii N, Nguyen NT, Marinkovich MP, Hashimoto T. Type VII collagen is the major autoantigen for sublamina densa-type linear IgA bullous dermatosis. J Invest Dermatol. 2015;135(2):626–9.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Ishiko A, Shimizu H, Masunaga T, Yancey KB, Giudice GJ, Zone JJ, et al. 97 kDa linear IgA bullous dermatosis antigen localizes in the lamina lucida between the NC16A and carboxyl terminal domains of the 180 kDa bullous pemphigoid antigen. J Invest Dermatol. 1998;111(1):93–6.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Paul C, Wolkenstein P, Prost C, Caux F, Rostoker G, et al. Drug-induced linear IgA disease: target antigens are heterogeneous. Br J Dermatol. 1997;136(3):406–11.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Selvaraj PK, Khasawneh FA. Linear IgA bullous dermatosis: a rare side effect of vancomycin. Ann Saudi Med. 2013;33(4):397–9.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Chanal J, Ingen-Housz-Oro S, Ortonne N, Duong TA, Thomas M, et al. Linear IgA bullous dermatosis: comparison between the drug-induced and spontaneous forms. Br J Dermatol. 2013;169(5):1041–8.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Kelly SE, Frith PA, Millard PR, et al. A clinicopathological study of mucosal involvement in linear IgA disease. Br J Dermatol. 1988;119(2):161–70.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Gotlieb J, Ingen-Housz-Oro S, Alexandre M, Grootenboer-Mignot S, Aucouturier F, et al. Idiopathic linear IgA bullous demratosis: prognostic factors based on a case series of 71 adults. Br J Dermatol. 2017;177(1):212–22.CrossRefGoogle Scholar
  59. 59.
    Bernett CN, Rosario-Collazo JA. Linear IGA dermatosis. StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2018.Google Scholar
  60. 60.
    El-Domyati M, Abdel-Wahab H, Ahmad H. Immunohistochemical localization of basement membrane laminin 5 and collagen IV in adult linear IgA disease. Int J Dermatol. 2015;54(8):922–8.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Garel B, Ingen-Housz-Oro S, Afriat D, Prost-Squarcioni C, Tetart F, et al. Drug-induced linear immunoglobulin A bullous dermatosis: a French retrospective pharmacovigilance study of 69 cases. Br J Clin Pharmacol. 2018;
  62. 62.
    Shimanovich I, Hirako Y, Sitaru C, et al. The autoantigen of anti-p200 pemphigoid is an acidic noncollagenous N-linked glycoprotein of the cutaneous basement membrane. J Invest Dermatol. 2003;121(6):1402–8.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Dainichi T, Kurono S, Ohyama B, et al. Anti-laminin gamma-1 pemphigoid. Proc Natl Acad Sci U S A. 2009;106(8):2800–5.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Dilling A, Rose C, Hashimoto T, Zillikens D, Shimanovich I. Anti-p200 pemphigoid: A novel autoimmune subepidermal blistering disease. J Dermatol. 2007;34(1):1–8.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Meijer JM, Diercks GF, Schmidt E, Pas HH, Jonkman MF. Laboratory diagnosis and clinical profile of anti-p200 pemphigoid. JAMA Dermatol. 2016;152(6):897–904.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Commin MH, Schmidt E, Duvert-Lehembre S, Lasek A, Morice C, et al. Clinical and immunological features and outcome of anti-p200 pemphigoid. Br J Dermatol. 2016;175(4):776–81.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Ohata C, Ishii N, Koga H, Fukuda S, Tateishi C, et al. Coexistence of autoimmune bullous diseases (AIBDs) and psoriasis: a series of 145 cases. J Am Acad Dermatol. 2015;73(1):50–5.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Goetze S, Dumke AK, Zillikens D, Hipler UC, Elsner P. Anti-p200/laminin gamma-1 pemphigoid associated with metastatic oesophageal cancer. J Eur Acad Dermatol Venereol. 2017;31(4):e219–21.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Hayashi M, Okamura K, Uijie H, Iwata H, Suzuki T. Case of anti-p200 pemphigoid accompanying uterine malignancy. J Dermatol. 2018;45(12):e341–2.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Rose C, Weyers W, Denisjuk N, Hillen U, Zillikens D, Shimanovich I. Histopathology of anti-p200 pemphigoid. Am J Dermatopathol. 2007;29(2):119–24.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Woodley DT, Briggaman RA, O’Keefe EJ, Inman AO, Queen LL, Gammon WR. Identification of the skin basement- membrane autoantigen in epidermolysis bullosa acquisita. N Engl J Med. 1984;310(16):1007–13.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Hubner F, Recke A, Zillikens D, Linder R, Schmidt E. Prevalence and age distribution of pemphigus and pemphigoid diseases in Germany. J Invest Dermatol. 2016;136(12):2495–8. Scholar
  73. 73.
    Koga H, Prost-Squarcioni C, Iwata H, Konkman MF, Ludwig J, Bieber K. Epidermolysis bullosa acquisita: the 2019 update. Front Med. 2019;5:362. Scholar
  74. 74.
    Prost-Squarcioni C, Caux F, Schmidt E, Jonkman MF, Vassileva S, et al. International Bullous Diseases Group: consensus on diagnostic criteria for epidermolysis bullosa acquisita. Br J Dermatol. 2018;179(1):30–41.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Vodegel RM, Jonkman MF, Pas HH, de Jong MC. U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases. Br J Dermatol. 2004;151(1):112–8.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Terra JB, Meijer JM, Jonkman MF, Diercks GF. The n- vs. u-serration is a learnable criterion to differentiate pemphigoid from epidermolysis bullosa acquisita in direct immunofluorescence serration pattern analysis. Br J Dermatol. 2013;169(1):100–5.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Meijer JM, Atefi I, Diercks GFH, Vorobyev A, Zuiderveen J, et al. Serration pattern analysis for differentiating epidermolysis bullosa acquisita from other pemphigoid diseases. J Am Acad Dermatol. 2018;78(4):754–759.e6.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Sebaratnam DF, Murrell DF. Bullous systemic lupus erythematosus. Dermatol Clin. 2011;29(4):649–53.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Chanprapaph K, Sawatwarakul S, Vachiramon V. A 12-year retrospective review of bullous systemic lupus erythematosus in cutaneous and systemic lupus erythematosus patients. Lupus. 2017;26(12):1278–84.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Pons-Estel GJ, Quintana R, Alarcon GS, Sacnun M, Ugarte-Gil MF, et al. A 12-year retrospective review of bullous systemic lupus erythematosus in cutaneous and systemic lupus erythematosus patients. Lupus. 2018;27(10):1753–4.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Chen M, Marinkovich P, Veis A. Interactions of the amino-terminal non-collagenous (NC1) domain of type VII collagen with extracellular matrix proteins. J Biol Chem. 1997;272(23):14516–22.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Chan LS, Lapiere JC, Chen M, et al. Bullous systemic lupus erythematosus with autoantibodies recognizing multiple skin basement membrane components, bullous pemphigoid antigen 1, laminin-5, laminin-6 and type VII collagen. Arch Dermatol. 1999;135(5):569–73.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Fujimoto W, Hamada T, Yamada J, Matsuura H, Iwatsuki K. Bullous systemic lupus erythematosus as an initial manifestation of SLE. J Dermatol. 2005;32(12):1021–7.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    De Risi-Pugliese T, Aubart FC, Haroche J, Moguelet P, Grootenboer-Mignot S, et al. Clinical, histological, immunological presentations and outcomes of bullous systemic lupus erythematosus: 10 new cases and a literature review of 118 cases. Semin Arthris Rheum. 2018;48(1):83–9.CrossRefGoogle Scholar
  85. 85.
    Nico MM, Lourenço SV. Multiple blisters along the lip vermilion are a clue to bullous lupus erythematosus. Acta Derm Venereol. 2012;92(4):404–5.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Vassileva S. Bullous systemic lupus erythematosus. Clin Dermatol. 2004;22(2):129–38.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Sardy M, Karpati S, Peterfy F, Rasky K, Tomsits E, et al. Comparison of a tissue transglutaminase ELISA with the endomysium antibody test in the diagnosis of gluten-sensitive enteropathy. Z Gastroenterol. 2000;38(5):357–64.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Cardones AR, Hall RP 3rd. Pathophysiology of dermatitis herpetiformis: a model for cutaneous manifestations of gastrointestinal inflammation. Immunol Allergy Clin N Am. 2012;32(2):263–74.CrossRefGoogle Scholar
  89. 89.
    Mobacken H, Kastrup W, Nilsson LA. Incidence and prevalence of dermatitis herpetiformis in western Sweden. Acta Derm Venereol. 1984;64(5):400–4.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Fry L. Dermatitis herpetiformis: problems, progress and prospects. Eur J Dermatol. 2002;12(6):523–31.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Rose C, Armbruster FP, Ruppert J, Igl BW, Zillikens D, Shimanovich I. Autoantibodies against epidermal transglutaminase are a sensitive diagnostic marker in patients with dermatitis herpetiformis on a normal or gluten-free diet. J Am Acad Dermatol. 2009;61:39–43.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Mendes FB, Hissa-Elian A, Abreu MA, Gonçalves VS. Review: dermatitis herpetiformis. An Bras Dermatol. 2013;88(4):594–9.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Caproni M, Antiga E, Melani L, Fabbri P, Italian Group for Cutaneous Immunopathology. Guidelines for the diagnosis and treatment of dermatitis herpetiformis. J Eur Acad Dermatol Venereol. 2009;23(6):633–8.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Lara-Corrales I, Pope E. Autoimmune blistering diseases in children. Semin Cutan Med Surg. 2010;29(2):85–91.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Collin P, Salmi TT, Hervonen K, Kaukinen K, Reunala T. Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease. Ann Med. 2017;49(1):23–31.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Bolotin D, Petronic-Rosic V. Dermatitis herpetiformis. Part II. Diagnosis, management, and prognosis. J Am Acad Dermatol. 2011;64(6):1027–33.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Barnadas MA. Dermatitis herpetiformis: a review of direct immunofluorescence findings. Am J Dermatopathol. 2016;38(4):283–8.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Dieterich W, Laag E, Bruckner-Tuderman L, Reunala T, Kárpáti S, et al. Antibodies to tissue transglutaminase as serologic markers in patients with dermatitis herpetiformis. J Invest Dermatol. 1999;113(1):133–6.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Zaraa I, Mahfoudh A, Sellami MK, Chelly I, El Euch D, et al. Lichen planus pemphigoides: four new cases and a review of the literature. Int J Dermatol. 2013;52(4):406–12.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Bouloc A, Vignon-Pennamen MD, Caux F, Teillac D, Wechsler J, et al. Lichen planus pemphigoides is a heterogeneous disease: a report of five cases studied by immunoelectron microscopy. Br J Dermatol. 1998;138(6):972–80.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Yoon KH, Kim SC, Kang DS, Lee IJ. Lichen planus pemphigoides with circulating autoantibodies against 200 and 180 kDa epidermal antigens. Eur J Dermatol. 2000;10(3):212–4.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Zillikens D, Caux F, Mascaro JM, et al. Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180. J Invest Dermatol. 1999;113(1):117–21.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Mignogna MD, Fortuna G, Leuci S, Stasio L, Mezza E, Ruoppo E. Lichen planus pemphigoides, a possible example of epitope spreading. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(6):837–43.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Schmidgen MI, Butsch F, Schadmand-Fischer S, Steinbrink K, Grabbe S, et al. Pembrolizumab-induced lichen planus pemphigoides in a patient with metastatic melanoma. J Disch Dermatol Ges. 2017;15(7):742–5.Google Scholar
  105. 105.
    Jang SH, Yun SJ, Lee SC, Lee JB. Lichen planus pemphigoides associated with chronic hepatitis B virus infection. Clin Exp Dermatol. 2015;40(8):868–71.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Sultan A, Stojanov IJ, Lerman MA, Kabani S, Haber J, Freedman J, Woo SB. Oral lichen planus pemphigoides: a series of four cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2015;120(1):58–68.CrossRefGoogle Scholar
  107. 107.
    Solomon LW, Helm TN, Stevens C, Neiders ME, Kumar V. Clinical and immunopathologic findings in oral lichen planus pemphigoides. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(6):808–13.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Schwieger-Briel A, Moellmann C, Mattulat B, Schauer F, Kiritsi D, Schmidt E, et al. Bullous pemphigoid in infants: characteristics, diagnosis and treatment. Orphanet J Rare Dis. 2014;9:185. Scholar
  109. 109.
    Bisherwal K, Pandhi D, Singal A, Sharma S. Infantile bullous pemphigoid following vaccination. Indian Pediatr. 2016;53(5):425–6.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Baykal C, Okan G, Sarica R. Childhood bullous pemphigoid developed after the first vaccination. J Am Acad Dermatol. 2001;44(2 Suppl):348–50.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    De la Fuente S, Hernandez-Martin A, de Lucas R, Gonzalez-Ensenat MA, Vicente A, et al. Postvaccination bullous pemphigoid in infancy: report of three new cases and literature review. Pediatr Dermatol. 2013;30(6):741–4.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Reis-Filho EG, Silva Tde A, Aguirre LH, Reis CM. Bullous pemphigoid in a 3-month-old infant: case report and literature review of this dermatosis in childhood. An Bras Dermatol. 2013;88(6):961–5.CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    McGrath JA, Schofield OM, Eady RA. Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features. Br J Dermatol. 1994;130(5):617–25.CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Christiano AM, Greenspan DS, Lee S, et al. Cloning of human type VII collagen. Complete primary sequence of the alpha 1 (VII) chain and identification of intragenic polymorphisms. J Biol Chem. 1994;269(32):20256–62.PubMedPubMedCentralGoogle Scholar
  115. 115.
    Kim WB, Alavi A, Pope E, Walsh S. Epidermolysis bullosa pruriginosa: case series and review of the literature. Int J Low Extrem Wounds. 2015;14(2):196–9.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Mellerio JE, Ashton GH, Mohammedi R, Lyon CC, Kirby B, et al. Allelic heterogeneity of dominant and recessive COL7A1 mutations underlying epidermolysis bullosa pruriginosa. J Invest Dermatol. 1999;112(6):984–7.CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Hayashi M, Kawaguchi M, Hozumi Y, Nakano H, Sawamura D, Suzuki T. Dystrophic epidermolysis bullosa pruriginosa of elderly onset. J Dermatol. 2011;38(2):173–8.CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Fernandes JD, Gabbi TV, Vilela MA, Sotto MN, Criado PR, Romiti R. Blisters on the legs. Clin Exp Dermatol. 2008;33(1):81–2.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Morimoto N, Shimizu A, Hattori M, Kuriyama Y, Nakano H, Ohnishi K. Dystrophic epidermolysis bullosa pruriginosa presenting with flagellate scarring lesions. Clin Exp Dermatol. 2019;44(2):e5–6.CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Nakamura E, Majima Y, Hashizume H, Tokura Y, Nakano H. Dominant dystrophic epidermolysis bullosa pruriginosa with a COL7A1 exon 87 c.6898C>T mutation. Clin Exp Dermatol. 2019;44(1):82–4.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of DermatologyFaculty of Medicine of the University of São PauloSão PauloBrazil
  2. 2.Department of PathologyMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

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