Oral Vesicular and Bullous Lesions

  • Stephen J. ChallacombeEmail author
  • Jane F. Setterfield
Reference work entry


Vesiculobullous disorders involving the oral cavity may also affect the skin and other mucous membranes. They may thus reflect the oral manifestations of dermatological conditions, especially those which are immune mediated. Several different types of vesiculobullous disorders may present or be seen in the oral cavity, and it is important that they be recognized as distinct from the many other types of oral ulceration since they may represent systemic disease. Successful management depends on this recognition. Thus, careful histories, clinical examination, an understanding of the pathogenesis, and appropriate investigations are essential.

Several of the vesiculobullous lesions are immune mediated. The most common and serious are mucous membrane pemphigoid (MMP) and pemphigus vulgaris, both of which are type II, antibody-mediated conditions. In contrast erythema multiforme is thought to be an immune complex-mediated condition (type III), and bullous lichen planus is a cell-mediated initiated condition (type IV). The etiology of angina bullosa hemorrhagica remains enigmatic but does not appear to be immune mediated, whereas those of dermatitis herpetiformis and linear IgA disease are immune related, one showing deposition of dimeric IgA linked to gut disease and the other monomeric IgA and not related to gut disease.

There have been recent advances in the understanding of target antigens in the MMP group of diseases in particular, which partially elucidates the question of antigen specificity and clinical phenotypes. At long last, the oral medicine field has begun to embrace disease severity scoring and clinical outcome measures. This has allowed an evidence base to the efficacy of immunosuppressive therapies in the treatment of vesiculobullous diseases. The continued development of biologics has led to consideration of monoclonal antibody therapy as a first-line treatment in pemphigus and other conditions.

Modern laboratory techniques have allowed much investigation into both target antigens and isotype specificity of antibodies. These have allowed the identification of new disease phenotypes which in turn, with application of disease severity scoring, has given an evidence base to treatments. There has been much investigation of the use of saliva in diagnostics of vesicular bullous lesions which suggest that saliva will be useful as an adjunct fluid to serum and in some cases as an alternative. Pemphigus and MMP are reported in detail as archetypal examples of immune-bullous conditions.


Vesicular conditions Bullous disease Vesiculobullous lesions Pemphigus vulgaris Paraneoplastic pemphigus Mucous membrane pemphigoid Erythema multiforme Linear IgA disease Angina bullosa hemorrhagica Epidermolysis bullosa acquisita Bullous lichen planus Dermatitis herpetiformis Disease severity scoring Evidence- based treatment Clinical outcomes Basement membrane zone Desmogleins BP180 Desmosomes Hemidesmosomes 


  1. Abé T, Maruyama S, Babkair H, Yamazaki M, Cheng J, Saku T. Simultaneous immunolocalization of desmoglein 3 and IgG4 in oral pemphigus vulgaris: IgG4 predominant autoantibodies in its pathogenesis. J Oral Pathol Med. 2015;44(10):850–6.PubMedCrossRefPubMedCentralGoogle Scholar
  2. Aboobaker J, Morar N, Ramdial PK, Hammond MG. Pemphigus in South Africa. Int J Dermatol. 2001;40:115–9.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Abreu-Velez AM, Hashimoto T, Bollag WB, et al. A unique form of endemic pemphigus in northern Colombia. J Am Acad Dermatol. 2003;49:599–608.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Ahmed AR, Hombal SM. Cicatricial pemphigoid. Int J Dermatol. 1986;25:90–6.PubMedCrossRefPubMedCentralGoogle Scholar
  5. Ahmed AR, Shetty SA. Comprehensive analysis of treatment outcomes in patients with pemphigus vulgaris treated with rituximab. Autoimmun Rev. 2015;14(4): 323–31.CrossRefGoogle Scholar
  6. Ahmed AR, Kurgis BS, Rogers IR. Cicatricial pemphigoid. J Am Acad Dermatol. 1991;24:987–1001.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006;355(17): 1772–9.PubMedCrossRefGoogle Scholar
  8. Alexandre M, Brette MD, Pascal F, Tsianakas P, Fraitag S, Doan S, Caux F, Dupuy A, Heller M, Lievre N, Lepage V, Dubertret L, Laroche L, Prost-Squarcioni C. A prospective study of upper aerodigestive tract manifestations of mucous membrane pemphigoid. Medicine. 2006;85:239–52.PubMedCrossRefPubMedCentralGoogle Scholar
  9. Ali S, Kelly C, Challacombe SJ, Donaldson AN, Bhogal BS, Setterfield JF. Serum and salivary IgG and IgA antibodies to Dsg3 in mucosal pemphigus vulgaris. Br J Dermatol. 2016a;175:113–21.CrossRefGoogle Scholar
  10. Ali S, Kelly C, Challacombe SJ, Donaldson AN, Dart JK, Gleeson M, MMP Study Group 2009-14, Setterfield J. Detection of salivary IgA and IgG antibodies to BP180-NC16a in mucous membrane pemphigoid patients as a diagnostic biomarker. Br J Dermatol. 2016b;174: 956–7.CrossRefGoogle Scholar
  11. Allen CM, Camisa C. Paraneoplastic pemphigus: a review of the literature. Oral Dis. 2000;6:208–14.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Alpsoy E, Akman-Karakas A, Uzun S. Geographic variations in epidemiology of two autoimmune bullous diseases: pemphigus and bullous pemphigoid. Arch Dermatol Res. 2015;307(4):291–8.PubMedCrossRefPubMedCentralGoogle Scholar
  13. Amagai M. Towards a better understanding of pemphigus autoimmunity. Br J Dermatol. 2000;143:237–8.PubMedCrossRefPubMedCentralGoogle Scholar
  14. Amagai M, Stanley JR. Desmoglein as a target in skin disease and beyond. J Invest Dermatol. 2012;132(3 pt 2):776–84.PubMedCrossRefPubMedCentralGoogle Scholar
  15. Amagai M, Nishikawa T, Nousari HC, Anhalt GJ, Hashimoto T. Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice. J Clin Invest. 1998;102(4): 775–82.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Amagai M, Ahmed AR, Kitajima Y, Bystryn JC, Milner Y, Gniadecki R, et al. Are desmoglein autoantibodies essential for the immunopathogenesis of pemphigus vulgaris, or just “witnesses of disease”? Exp Dermatol. 2006;15(10):815–31.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Amber KT, Staropoli P, Shiman MI, Elgart GW, Hertl M, Autoreactive T. Cells in the immune pathogenesis of pemphigus vulgaris. Exp Dermatol. 2013;22(11): 699–704.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 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. 2017.Google Scholar
  19. Andreadis D, Lorenzini G, Drakoulakos D, Belazi M, Mihailidou E, Velkos G, Mourellou-Tsatsou O, Antoniades D. Detection of pemphigus desmoglein 1 and desmoglein 3 autoantibodies and pemphigoid BP180 autoantibodies in saliva and comparison with serum values. Eur J Oral Sci. 2006;114(5):374–80.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Anhalt GJ. Paraneoplastic pemphigus. Adv Dermatol. 1997;12:77.PubMedPubMedCentralGoogle Scholar
  21. Anhalt GJ. Paraneoplastic pemphigus. J Investig Dermatol Symp Proc. 2004;9:29–33.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Anhalt GJ, Kim SC, et al. Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med. 1990;323:1729–35.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Arduino PG, Farci V, D’Aiuto F, et al. Periodontal status in oral mucous membrane pemphigoid: initial results of a case-control study. Oral Dis. 2011;17(1):90–4.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Arduino PG, Lopetuso E, Carcieri P, et al. Professional oral hygiene treatment and detailed oral hygiene instructions in patients affected by mucous membrane pemphigoid with specific gingival localization: a pilot study in 12 patients. Int J Dent Hyg. 2012;10(2): 138–41.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Ayangco L, Rogers RS 3rd. Oral manifestations of erythema multiforme. Dermatol Clin. 2003;21(1): 195–205.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Barnados MA. Dermatitis herpetiformis: a review of direct immunofluorescence findings. Am J Dermatopathol. 2016;38(4):283–8.CrossRefGoogle Scholar
  27. Baum S, Astman N, Berco E, Solomon M, Trau H, Barzilai A. Epidemiological data of 290 pemphigus vulgaris patients: a 29-year retrospective study. Eur J Dermatol. 2016;26(4):382–7.PubMedPubMedCentralGoogle Scholar
  28. Bean SF, Waisman M, Michel B, Thomas CI, Knox JM, Levine M. Cicatricial pemphigoid. Immunofluorescent studies. Arch Dermatol. 1972;106:195–9.PubMedCrossRefPubMedCentralGoogle Scholar
  29. Bernard P, Vaillant L, Labeille B, Bedane C, Arbeille B, Denoeux JP, Lorette G, Bonnetblanc JM, Prost C. Incidence and distribution of subepidermal autoimmune bullous skin diseases in three French regions. Bullous Diseases French Study Group. Arch Dermatol. 1995;131:48–52.PubMedCrossRefGoogle Scholar
  30. Beutner EH, Rhodes EL, Holborow EJ. Autoimmunity in chronic bullous skin diseases. Immunofluorescent demonstration of three types of antibodies to skin in sera of patients with pemphigus, bullous pemphigoid and in other human sera. Clin Exp Immunol. 1967;2(2): 141–51.PubMedPubMedCentralGoogle Scholar
  31. Bhol K, Natarajan K, Nagarwalla N, Mohimen A, Aoki V, Ahmed AR. Correlation of peptide specificity and IgG subclass with pathogenic and nonpathogenic autoantibodies in pemphigus vulgaris: a model for autoimmunity. Proc Natl Acad Sci USA. 1995;92(11):5239–43.PubMedCrossRefPubMedCentralGoogle Scholar
  32. Bhol KC, Goss L, Kumari S, Colon JE, Ahmed AR. Autoantibodies to human alpha6 integrin in patients with oral pemphigoid. J Dent Res. 2001;80:1711–5.PubMedCrossRefPubMedCentralGoogle Scholar
  33. Bieber K, Sun S, Ishii N, Kasperkiewicz M, Schmidt E, Hirose M, Westermann J, Yu X, Zillikens D, Ludwig R. Animal models for autoimmune bulous dermatoses. Exp Dermatol. 2009;19:2–11.PubMedCrossRefPubMedCentralGoogle Scholar
  34. Borradori L, Sonnenberg A. Structure and function of hemidesmosomes: more than simple adhesion complexes. J Invest Dermatol. 1999;112:411–8.PubMedCrossRefPubMedCentralGoogle Scholar
  35. Brochado MJ, Nascimento DF, Campos W, Deghaide NH, Donadi EA, Roselino AM, Differential HLA. Class I and class II associations in pemphigus foliaceus and pemphigus vulgaris patients from a prevalent southeastern Brazilian region. J Autoimmun. 2016;72: 19–24.PubMedCrossRefPubMedCentralGoogle Scholar
  36. Brunsting L, Perry H. Benign Pemphigoid? A report of seven cases with chronic scarring, herpetiform plaques about the head and neck. Arch Dermatol. 1957;75: 489–501.CrossRefGoogle Scholar
  37. Bunker CB. Male genital skin disease. Edinburgh: Saunders; 2004.Google Scholar
  38. Butt Z, Kaufman D, McNab A, McKelvie P. Drug-induced ocular cicatricial pemphigoid: a series of clinicopathological reports. Eye. 1998;12(Pt 2):285–90.PubMedCrossRefPubMedCentralGoogle Scholar
  39. Buxton RS, Magee AI. Structure and interactions of desmosomal and other cadherins. Semin Cell Biol. 1992;3(3):157–67. Review.PubMedCrossRefPubMedCentralGoogle Scholar
  40. Capon F, Boulding H, Quaranta M, et al. Genetic analysis of desmoglein 3 (DSG3) sequence variants in patients with pemphigus vulgaris. Br J Dermatol. 2009;161(6): 1403–5.PubMedCrossRefPubMedCentralGoogle Scholar
  41. Carrozzo M, Gandolfo S, Lodi G, Carbone M, Garzino-Demo P, Carbonero C, et al. Oral lichen planus in patients infected or non infected with the hepatitis C virus: the role of autoimmunity. J Oral Pathol Med. 1999;28:16–19.Google Scholar
  42. Carrozzo M, Fasano ME, Broccoletti R, Carbone M, Cozzani E, Rendine S, Roggero S, Parodi A, Gandolfo S. HLA-DQB1 alleles in Italian patients with mucous membrane pemphigoid predominantly affecting the oral cavity. Br J Dermatol. 2001;145: 805–8.PubMedCrossRefPubMedCentralGoogle Scholar
  43. Carrozzo M, Dametto E, Fasano ME, et al. Interleukin-4RA gene polymorphism is associated with oral mucous membrane pemphigoid. Oral Dis. 2014;20: 275–80.PubMedCrossRefPubMedCentralGoogle Scholar
  44. Celentano A, Tovaru S, Yap T, Adamo D, Aria M, Mignogna MD. Oral erythema multiforme: trends and clinical findings of a large retrospective European case series. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(6):707–16.PubMedCrossRefPubMedCentralGoogle Scholar
  45. Challacombe SJ, Setterfield J, Shirlaw P, Harman K, Scully C, Black MM. Immunodiagnosis of pemphigus and mucous membrane pemphigoid. Acta Odontol Scand. 2001;59:226–34.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Challacombe SJ, Shirlaw PJ, Thornhill MH. Immunology of diseases of the oral cavity. Chapter 102. In: Mestecky J, Strober W, Russell MW, Kelsall BL, Cheroutre H, Lambrecht BN, editors. Mucosal immunology. 4th ed. St Louis: Elsevier Ltd; 2016. p. 1943–83.Google Scholar
  47. Chams-Davatchi C, Valikhani M, Daneshpazhooh M, et al. Pemphigus: analysis of 1209 cases of pemphigus vulgaris and pemphigus foliaceus. Int J Dermatol. 2005;44:470–6.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Chams-Davatchi C, Esmaili N, Daneshpazhooh M, et al. Randomized controlled open label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol. 2007;57:622–8.PubMedCrossRefPubMedCentralGoogle Scholar
  49. Chan LS, Soong HK, Foster CS, Hammerberg C, Cooper KD. Ocular cicatricial pemphigoid occurring as a sequela of Stevens-Johnson syndrome. JAMA. 1991;266:1543–6.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Chan LS, Yancey KB, Hammerberg C, Soong HK, Regezi JA, Johnson K, Cooper KD. Immune-mediated subepithelial blistering diseases of mucous membranes: pure ocular cicatricial pemphigoid is a unique clinical and immunopathological entity distinct from bullous pemphigoid and other subsets identified by antigenic specificity of autoantibodies. Arch Dermatol. 1993;129:448–55.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Chan LS, Wang T, Wang XS, Hammerberg C, Cooper KD. High frequency of HLA-DQB1*0301 allele in patients with pure ocular cicatricial pemphigoid. Dermatology. 1994;189(Suppl 1):99–101.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Chan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, et al. The first international consensus mucous membrane pemphigoid: definition, diagnostic criteria, pathogenetic factors, medical treatment and prognostic indicators. Arch Dermatol. 2002;138(3):370–9.CrossRefGoogle Scholar
  53. Chen M, Keene DR, Costa FK, Tahk SH, Woodley DT. The carboxyl terminus of type VII collagen mediates antiparallel dimer formation and constitutes a new antigenic epitope for epidermolysis Bullosa acquisita autoantibodies. J Biol Chem. 2001;276(24):21649–55.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Chen J, Zheng Q, Hammers CM, Ellebrecht CT, Mukherjee EM, Tang HY, Lin C, Yuan H, Pan M, Langenhan J, Komorowski L, Siegel DL, Payne AS, Stanley JR. Proteomic analysis of pemphigus autoantibodies indicates a larger, more diverse, and more dynamic repertoire than determined by B cell genetics. Cell Rep. 2017;18(1):237–47.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Chorzelski TP, Jablonska S. IgA linear dermatosis of childhood (chronic bullous disease of childhood). Br J Dermatol. 1979;101:535–42.PubMedCrossRefPubMedCentralGoogle Scholar
  56. Civatte A. Le diagnostic des dermatoses bulleuses au laboratoire. Arch Belg Dermatol Syphiligr. 1949;5: 273–5.PubMedPubMedCentralGoogle Scholar
  57. Collina P, Salmi TT, Hervonen K, Kaukinen K, Reunala T. Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease. Ann Med. 2017;49(1):23–31.CrossRefGoogle Scholar
  58. Commin MH, Schmidt E, Duvert-Lehembre S, Lasek A, Morice C, Estival JL, Debarbieux S, Rigal E, Pauwels C, De Quatrebarbes J, Roussel A, Goujon E, Stoebner PE, Jouen F, Joly P. Clinical and immunological features and outcome of anti-p200pemphigoid. Br J Dermatol. 2016;175:776–81.PubMedCrossRefPubMedCentralGoogle Scholar
  59. Conejo-Mir JS, del Canto S, Muñoz MA, Rodríguez-Freire L, Serrano A, Hernandez C, Pulpillo A. Thalidomide as elective treatment in persistent erythema multiforme; report of two cases. J Drugs Dermatol. 2003;2(1):40–4.PubMedPubMedCentralGoogle Scholar
  60. Cozzani E, Di Zenzo G, Calabresi V, Caproni M, Schena D, Quaglino P, Marzano AV, Fabbri P, Rebora A, Parodi A. Anti-desmoplakin antibodies in erythema multiforme and Stevens-Johnson syndrome sera: pathogenic or epiphenomenon? Eur J Dermatol. 2011;21(1):32–6.PubMedPubMedCentralGoogle Scholar
  61. Cozzani E, Di Zenzo G, Calabresi V, Carrozzo M, Burlando M, Longanesi L, Cerri A, Caproni M, Sera F, Antiga E, Quaglino P, Marzano AV, Parodi A. Autoantibody profile of a cohort of 78 Italian patients with mucous membrane pemphigoid: correlation between reactivity profile and clinical involvement. Acta Derm Venereol. 2016;96(6):768–73.PubMedPubMedCentralGoogle Scholar
  62. Culton DA, Qian Y, Li N, et al. Advances in pemphigus and its endemic pemphigus foliaceus (Fogo Selvagem) phenotype: a paradigm of human autoimmunity. J Autoimmun. 2008;31:311–24.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Culton DA, McCray SK, Park M, Roberts JC, Li N, Zedek DC, Anhalt GJ, Cowley DO, Liu Z, Diaz LA. Mucosal pemphigus vulgaris anti-Dsg3 IgG is pathogenic to the oral mucosa of humanized Dsg3 mice. J Invest Dermatol. 2015;135(6):1590–7.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Dainichi T, Kurono S, Ohyama B, Ishii N, Sanzen N, Hayashi M, Shimono C, Taniguchi Y, Koga H, Karashima T, Yasumoto S, Zillikens D, Sekiguchi K, Hashimoto T. Anti-laminin gamma-1 pemphigoid. Proc Natl Acad Sci USA. 2009;106:2800–5.PubMedCrossRefPubMedCentralGoogle Scholar
  65. Dantzig P. Circulating antibodies in cicatricial pemphigoid. Arch Dermatol. 1973;108:264–6.PubMedCrossRefPubMedCentralGoogle Scholar
  66. Dart JK. The 2016 Bowman lecture conjunctival curses: scarring conjunctivitis 30 years on. Eye (Lond). 2017;31:301–32.CrossRefGoogle Scholar
  67. De Rojas MV, Dart JK, Saw VP. The natural history of Stevens Johnson syndrome: patterns of chronic ocular disease and the role of systemic immunosuppressive therapy. Br J Ophthalmol. 2007;91:1048–53.PubMedPubMedCentralCrossRefGoogle Scholar
  68. Delgado JC, Turbay D, Yunis EJ, Yunis JJ, Morton ED, Bhol K, Norman R, Alper CA, Good RA, Ahmed R. A common major histocompatibility complex class II allele HLA-DQB1*0301 is present in clinical variants of pemphigoid. Proc Natl Acad Sci USA. 1996;93: 8569–71.PubMedCrossRefPubMedCentralGoogle Scholar
  69. Di Zenzo G, Carrozzo M, Chan LS. Urban legend series: mucous membrane pemphigoid. Oral Dis. 2014;20(1): 35–54.CrossRefGoogle Scholar
  70. Dobrev H, Popova L, Vlashev D. Proteinase inhibitors and pemphigus vulgaris. An in vitro and in vivo study. Arch Dermatol Res. 1996;288(11):648–55.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Drouet M, Delpuget-Bertin N, Vaillant L, Chauchaix S, Boulanger MD, Bonnetblanc JM, Bernard P. HLA-DRB1 and HLA-DQB1 genes in susceptibility and resistance to cicatricial pemphigoid in French Caucasians. Eur J Dermatol. 1998;8:330–3.PubMedPubMedCentralGoogle Scholar
  72. Egan CA, Lazarova Z, Darling TN, Yee C, Cote T, Yancey KB. Anti-epiligrin cicatricial pemphigoid and relative risk for cancer. Lancet. 2001;357:1850–1.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Egu DT, Walter E, Spindler V, Waschke J. Inhibition of p38MAPK signalling prevents epidermal blistering and alterations of desmosome structure induced by pemphigus autoantibodies in human epidermis. Br J Dermatol. 2017Google Scholar
  74. Elias PM, Matsuyoshi N, Wu H, et al. Desmoglein isoform distribution affects stratum corneum structure and function. J Cell Biol. 2001;153(2):243–50.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Ellebrecht CT, Payne AS. Setting the target for pemphigus vulgaris therapy. JCI Insight. 2017;2(5):e92021. Review.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Ellebrecht CT, Bhoj VG, Nace A, Choi EJ, Mao X, Cho MJ, Di Zenzo G, Lanzavecchia A, Seykora JT, Cotsarelis G, Milone MC, Payne AS. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science. 2016;353(6295): 179–84.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Eming R, Hennerici T, Bäcklund J, Feliciani C, Visconti KC, Willenborg S, Wohde J, Holmdahl R, Sønderstrup G, Hertl M. Pathogenic IgG antibodies against desmoglein 3 in pemphigus vulgaris are regulated by HLA-DRB1*04:02-restricted T cells. J Immunol. 2014;193(9):4391–9.PubMedCrossRefPubMedCentralGoogle Scholar
  78. Escudier M, Ahmed N, Shirlaw P, et al. A scoring system for mucosal disease severity with special reference to oral lichen planus. Br J Dermatol. 2007;157(4):765–70.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Eyre RW, Stanley JR. Identification of pemphigus vulgaris antigen extracted from normal human epidermis and comparison with pemphigus foliaceus antigen. J Clin Investig. 1988;81(3):807–12.PubMedCrossRefPubMedCentralGoogle Scholar
  80. Fainaru O, Mashiach R, Kupferminc M, Shenhav M, Pauzner D, Lessing JB. Pemphigus vulgaris in pregnancy: a case report and review of literature. Hum Reprod. 2000;15(5):1195–7. Review.PubMedCrossRefPubMedCentralGoogle Scholar
  81. Farthing P, Bagan JV, Scully C. Mucosal disease series. Number IV. Erythema multiforme. Oral Dis. 2005;11(5):261–7.PubMedCrossRefGoogle Scholar
  82. Fortuna G, Marinkovich P. Linear immunoglobulin A bullous dermatosis. Clin Dermatol. 2012;30:38–50.PubMedCrossRefPubMedCentralGoogle Scholar
  83. Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc. 1986;84:527–663.PubMedPubMedCentralGoogle Scholar
  84. Gallagher G, Shklar G. Oral involvement in mucous membrane pemphigoid. Clin Dermatol. 1987;5:18–27.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Gandhi K, Chen M, Aasi S, Lapiere JC, Woodley DT, Chan LS. Autoantibodies to type VII collagen have heterogeneous subclass and light chain compositions and their complement-activating capacities do not correlate with the inflammatory clinical phenotype. J Clin Immunol. 2000;20(6):416–23.PubMedCrossRefPubMedCentralGoogle Scholar
  86. Ghalayani P, Rashidi F, Saberi Z. Assessment of IgG antibodies against HSV1, HSV2, CMV and EBV in patients with pemphigus vulgaris versus healthy people. J Dent (Tehran). 2015;12(11):835–40.Google Scholar
  87. Gniadecki R. Desmoglein autoimmunity in the pathogenesis of pemphigus. Autoimmunity. 2006;39(7):541–7. Review.PubMedCrossRefPubMedCentralGoogle Scholar
  88. Grando SA, Pittelkow MR, Schallreuter KU. Adrenergic and cholinergic control in the biology of epidermis: physiological and clinical significance. J Invest Dermatol. 2006;126(9):1948–65.PubMedCrossRefPubMedCentralGoogle Scholar
  89. Grau AE, Setterfield J, Saw VPJ. How to do conjunctival and buccal biopsies to investigate cicatrising conjunctivitis: improving the diagnosis of ocular mucous membrane pemphigoid. Br J Ophthalmol. 2013;97:530–1 and 537–8.PubMedCrossRefPubMedCentralGoogle Scholar
  90. Greenblatt DT, Benton EC, Groves RW, Setterfield JF. Crescendo response to rituximab in oral pemphigus vulgaris: a case with 7-year follow-up. Clin Exp Dermatol. 2016;41(5):529–32.PubMedCrossRefPubMedCentralGoogle Scholar
  91. Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes Bavinck JN, Sidoroff A, Naldi L, Dunant A, Viboud C, Roujeau JC, EuroSCAR study group. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol. 2008;58(1):25–32.PubMedCrossRefPubMedCentralGoogle Scholar
  92. Hallaji Z, Mortazavi H, Lajevardi V, Tamizifar B, AmirZargar A, Daneshpazhooh M, Chams-Davatchi C. Serum and salivary desmoglein 1 and 3 enzyme-linked immunosorbent assay in pemphigus vulgaris: correlation with phenotype and severity. J Eur Acad Dermatol Venereol. 2010;24(3):275–80.PubMedCrossRefPubMedCentralGoogle Scholar
  93. Hammers CM, Stanley JR. Mechanisms of disease: pemphigus and bullous pemphigoid. Annu Rev Pathol. 2016;11:175–97.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Hammers CM, Chen J, Lin C, et al. Persistence of anti-desmoglein 3 IgG + B-cell clones in pemphigus patients over years. J Invest Dermatol. 2015;135(3):742–9.PubMedCrossRefPubMedCentralGoogle Scholar
  95. Hardy KM, Perry HO, Pingree GC, Kirby TJ Jr. Benign mucous membrane pemphigoid. Arch Dermatol. 1971;104:467–75.PubMedCrossRefPubMedCentralGoogle Scholar
  96. Harfouch E, Daoud S. Allelic variation in HLA-DRB1* loci in Syrian pemphigus vulgaris patients. Int J Dermatol. 2014;53(12):1460–3.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Harman KE, Gratian MJ, Seed PT, Bhogal BS, Challacombe SJ, Black MM. An evaluation of ELISA for detection of antibodies to the major pemphigus antigens, desmoglein 1 and 3: a sensitive tool to aid the diagnosis and differentiation of pemphigus vulgaris and foliaceus. Clin Exp Dermatol. 2000a;25:236–40.PubMedCrossRefPubMedCentralGoogle Scholar
  98. Harman KE, Gratian MJ, Bhogal BS, Challacombe SJ, Black MM. A study of desmoglein 1 autoantibodies in pemphigus vulgaris: racial differences in frequency and the association with a more severe phenotype. Br J Dermatol. 2000b;142:343–8.CrossRefGoogle Scholar
  99. Harman KE, Seed PT, Gratian MJ, Bhogal BS, Challacombe SJ, Black MM. The severity of cutaneous and oral pemphigus is related to desmoglein 1 and 3 antibody levels. Br J Dermatol. 2001;144:775–80.PubMedCrossRefGoogle Scholar
  100. Harman KE, Setterfield JF, Shirlaw PJ, Black MM, Challacombe SJ. Clinicopathological case 1: mucous membrane pemphigoid, epidermolysis bullosa acquisita and linear immunoglobulin A disease. Clin Exp Dermatol. 2003;28:461–2.PubMedCrossRefPubMedCentralGoogle Scholar
  101. Harman KE, Brown D, Exton LS, Groves RW, Hampton PJ, Mohd Mustapa MF, Setterfield JF, Yesudian PD. British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol. 2017;177:1170–1201.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Hashimoto T. Immunopathology of paraneoplastic pemphigus. Clin Dermatol. 2001;19:675–82.PubMedCrossRefPubMedCentralGoogle Scholar
  103. Hayakawa T, Furumura M, Fukano H, et al. Diagnosis of oral mucous membrane pemphigoid by means of combined serologic testing. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:483–96.PubMedCrossRefPubMedCentralGoogle Scholar
  104. Hennerici T, Pollmann R, Schmidt T, Seipelt M, Tackenberg B, Möbs C, Ghoreschi K, Hertl M, Eming R. Increased frequency of T follicular helper cells and elevated Interleukin-27 plasma levels in patients with pemphigus. PLoS One. 2016;11(2):e0148919.PubMedPubMedCentralCrossRefGoogle Scholar
  105. Herbst A, Bystryn JC. Patterns of remission in pemphigus vulgaris.J Am Acad Dermatol. 2000;42(3):422–7.PubMedCrossRefPubMedCentralGoogle Scholar
  106. Hertl M, Riechers R. Autoreactive T cells as potential targets for immunotherapy of autoimmune bullous skin diseases. Clin Dermatol. 2001;19(5):592–7. Review.PubMedCrossRefPubMedCentralGoogle Scholar
  107. Hertl M, Veldman C. T-cellular autoimmunity against desmogleins in pemphigus, an autoantibody-mediated bullous disorder of the skin. Autoimmun Rev. 2003;2(5):278–83. Review.PubMedCrossRefPubMedCentralGoogle Scholar
  108. Hirsch G, Ingen-Housz-Oro S, Fite C, Valeyrie-Allanore L, Ortonne N, Buffard V, Verlinde-Carvalho M, Marinho E, Martinet J, Grootenboer-Mignot S, Descamps V, Wolkenstein P, Joly P, Chosidow O. Rituximab, a new treatment for difficult-to-treat chronic erythema multiforme major? Five cases. J Eur Acad Dermatol Venereol. 2016;30(7):1140–3.PubMedCrossRefPubMedCentralGoogle Scholar
  109. Huang C, Chen S, Liu Z, Tao J, Wang C, Zhou Y. Familial bullous lichen planus (FBLP): pedigree analysis and clinical characteristics. J Cutan Med Surg. 2005;9:217–22.PubMedCrossRefPubMedCentralGoogle Scholar
  110. Hübner F, Recke A, Zillikens D, Linder R, Schmidt E. Prevalence and age distribution of pemphigus and pemphigoid diseases in Germany. J Invest Dermatol. 2016;136:2495–8.PubMedCrossRefPubMedCentralGoogle Scholar
  111. Izumi K, Nishie W, Mai Y, Wada M, Natsuga K,Ujiie H, et al. Autoantibody profile differentiates between inflammatory and noninflammatory bullous pemphigoid. J Invest Dermatol. 2016;136:2201e10.PubMedCrossRefPubMedCentralGoogle Scholar
  112. Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, French study group on autoimmune bullous skin diseases, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet. 2017;389(10083):2031–40.CrossRefGoogle Scholar
  113. Kaçar N, Cevahir N, Demirkan N, Şanlı B. The investigation of the possible relationship between Coxsackie viruses and pemphigus. Int J Dermatol. 2014;53(3): 312–5.PubMedCrossRefPubMedCentralGoogle Scholar
  114. Kardos M, Levine D, Gürcan HM, Ahmed RA. Pemphigus vulgaris in pregnancy: analysis of current data on the management and outcomes. Obstet Gynecol Surv. 2009;64(11):739–49.PubMedCrossRefPubMedCentralGoogle Scholar
  115. Kartan S, Shi VY, Clark AK, Chan LS. Paraneoplastic pemphigus and autoimmune blistering diseases associated with neoplasm: characteristics, diagnosis, associated neoplasms, proposed pathogenesis, treatment. Am J Clin Dermatol. 2017;18(1):105–26.PubMedCrossRefPubMedCentralGoogle Scholar
  116. Khullar G, De D, Narang T, Saikia UN, Handa S. Pemphigus vegetans localized to unusual sites. Indian J Dermatol Venereol Leprol. 2015;81(5):509–11.PubMedCrossRefPubMedCentralGoogle Scholar
  117. Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. Interventions for mucous membrane pemphigoid and epidermolysis bullosa acquisita. Cochrane Database Syst Rev. 2003;(1):CD004056. ReviewGoogle Scholar
  118. Kokkonen N, Herukka SK, Huilaja L, Kokki M, Koivisto AM, Hartikainen P, et al. Increased levels of the bullous pemphigoid BP180 autoantibody are associated with more severe dementia in Alzheimer’s disease. J Invest Dermatol. 2017;137:71–6.PubMedCrossRefPubMedCentralGoogle Scholar
  119. Kokuba H, Aurelian L, Burnett J. Herpes simplex virus associated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-gamma is expressed in HAEM lesions and tumor necrosis factor-alpha in drug-induced erythema multiforme lesions. J Invest Dermatol. 1999;113(5):808–15.PubMedCrossRefPubMedCentralGoogle Scholar
  120. Korman N. Pemphigus. J Am Acad Dermatol. 1988;18(6):1219–38. Review.Google Scholar
  121. Korman N. Pemphigus. J Am Acad Dermatol. 1988;18(6):1219–38. Review. PMID: 3290286.Google Scholar
  122. Kowalczyk AP, Green KJ. Structure, function and regulation of desmosomes. Prog Mol Biol Transl Sci. 2013;116:95–118.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Kricheli D, David M, Frusic-Zlotkin M, Goldsmith D, Rabinov M, Sulkes J, Milner Y. The distribution of pemphigus vulgaris-IgG subclasses and their reactivity with desmoglein 3 and 1 in pemphigus patients and their first-degree relatives. Br J Dermatol. 2000;143(2):337–42.PubMedCrossRefPubMedCentralGoogle Scholar
  124. Kridin K, Zelber-Sagi S, Khamaisi M, Cohen AD, Bergman R. Remarkable differences in the epidemiology of pemphigus among two ethnic populations in the same geographic region. J Am Acad Dermatol. 2016;75(5):925–30.PubMedCrossRefPubMedCentralGoogle Scholar
  125. Kridin K, Zelber-Sagi S, Bergman R. Pemphigus vulgaris and pemphigus foliaceus: differences in epidemiology and mortality. Acta Derm Venereol. 2017.Google Scholar
  126. Kumar S, De D, Handa S, Ratho RK, Bhandari S, Pal A, Kamboj P, Sarkar S. Identification of factors associated with treatment refractoriness of oral lesions in pemphigus vulgaris. Br J Dermatol. 2017.Google Scholar
  127. Kurata M, Mizukawa Y, Aoyama Y, Shiohara T. Herpes simplex virus reactivation as a trigger of mucous lesions in pemphigus vulgaris. Br J Dermatol. 2014;171(3):554–60.PubMedCrossRefPubMedCentralGoogle Scholar
  128. Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJ, West J. Bullous pemphigoid and pemphigus vulgaris – incidence and mortality in the UK: population based cohort study. BMJ. 2008;337:a180.PubMedCrossRefPubMedCentralGoogle Scholar
  129. Lara-Corrales I, Pope E. Autoimmune blistering diseases in children. Semin Cutan Med Surg. 2010;29(2):85–91.PubMedCrossRefPubMedCentralGoogle Scholar
  130. Laskaris G, Sklavounou A, Stratigos J. Bullous pemphigoid, cicatricial pemphigoid, and pemphigus vulgaris. A comparative clinical survey of 278 cases. Oral Surg Oral Med Oral Pathol. 1982;54:656–62.PubMedCrossRefPubMedCentralGoogle Scholar
  131. Le Roux-Villet C, Prost-Squarcioni C, Alexandre M, Caux F, Pascal F, Doan S, et al. Rituximab for patients with refractory mucous membrane pemphigoid. Arch Dermatol. 2011;147:843–9.PubMedCrossRefPubMedCentralGoogle Scholar
  132. Léauté-Labrèze C, Lamireau T, Chawki D, Maleville J, Taïeb A. Diagnosis, classification, and management of erythema multiforme and Stevens-Johnson syndrome. Arch Dis Child. 2000;83(4):347–52.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Lee MS, Wakefield PE, Konzelman JL Jr, James WD. Oral insertable prosthetic device as an aid in treating oral ulcers. Arch Dermatol. 1991;127(4):479–80.PubMedCrossRefPubMedCentralGoogle Scholar
  134. Lever W. Pemphigus: a histopathologic study. Arch Dermatol. 1951;64:727–53.Google Scholar
  135. Lever W. Commentary on Brunsting LA, Perry HO. Benign pemphigoid? A report of seven cases with chronic, scarring, herpetiform plaques about the head and neck. Arch Dermatol. 1957;75:489–501.Google Scholar
  136. Li X, Qian H, Sogame R, et al. Integrin β4 is a major target antigen in pure ocular mucous membrane pemphigoid. European Journal of Dermatology. 2016;1;26(3):247–53.Google Scholar
  137. Liakopoulou A, Rallis E. Bullous lichen planus – a review. J Dermatol Case Rep. 2017;11(1):1–4.PubMedPubMedCentralCrossRefGoogle Scholar
  138. Loiseau P, Lecleach L, Prost C, Lepage V, Busson M, Bastuji-Garin S, Roujeau JC, Charron D. HLA class II polymorphism contributes to specify desmoglein derived peptides in pemphigus vulgaris and pemphigus foliaceus. J Autoimmun. 2000;15(1):67–73.PubMedCrossRefPubMedCentralGoogle Scholar
  139. Ludwig RJ. Clinical presentation, pathogenesis, diagnosis, and treatment of epidermolysis bullosa acquisita. ISRN Dermatol. 2013;2013:812029.PubMedPubMedCentralCrossRefGoogle Scholar
  140. Mahoney MG, Wang Z, Rothenberger K, Koch PJ, Amagai M, Stanley JR. Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris. J Clin Investig. 1999;103(4): 461–8.PubMedCrossRefPubMedCentralGoogle Scholar
  141. Maley A, Warren M, Haberman I, Swerlick R, Kharod-Dholakia B, Feldman R. Rituximab combined with conventional therapy versus conventional therapy alone for the treatment of mucous membrane pemphigoid (MMP). J Am Acad Dermatol. 2016;74:835–40.PubMedCrossRefPubMedCentralGoogle Scholar
  142. Mansikka E, Hervonen K, Salmi TT, Kautiainen H, Kaukinen K, Collin P, Reunala T. The decreasing prevalence of severe villous atrophy in dermatitis herpetiformis. A 45-year experience in 393 patients. J Clin Gastroenterol. 2017;51:235–9.PubMedPubMedCentralGoogle Scholar
  143. Martin LK, Werth V, Villanueva E, et al. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev. 2009;(1):CD006263.Google Scholar
  144. McMillan R, Taylor J, Shephard M, Ahmed R, Carrozzo M, Setterfield J, et al. World workshop on oral medicine VI: a systematic review of the treatment of mucocutaneous pemphigus vulgaris. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(2):132–42.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Mehren CR, Gniadecki R. Epidermolysis bullosa acquisita: current diagnosis and therapy. Dermatol Reports. 2011;3(3):e38.PubMedPubMedCentralCrossRefGoogle Scholar
  146. Milinković MV, Janković S, Medenica L, Nikolić M, Reljić V, Popadić S, Janković J. Incidence of autoimmune bullous diseases in Serbia: a 20-year retrospective study. J Dtsch Dermatol Ges. 2016;14(10): 995–1005.PubMedPubMedCentralGoogle Scholar
  147. Miyagawa S, Amagai M, Iida T, Yamamoto Y, Nishikawa T, Shirai T. Late development of antidesmoglein 1 antibodies in pemphigus vulgaris: correlation with disease progression. Br J Dermatol. 1999a;141(6):1084–7.PubMedCrossRefPubMedCentralGoogle Scholar
  148. Miyagawa S, Amagai M, Niizeki H, Yamashina Y, Kaneshige T, Nishikawa T, Shirai T, Inoko H. HLA-DRB1 polymorphisms and autoimmune responses to desmogleins in Japanese patients with pemphigus. Tissue Antigens. 1999b;54(4):333–40.PubMedCrossRefPubMedCentralGoogle Scholar
  149. Mobini N, Nagarwalla N, Ahmed AR. Oral pemphigoid. Subset of cicatricial pemphigoid? Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85(1):37–43.PubMedCrossRefPubMedCentralGoogle Scholar
  150. Mondino BJ, Brown SI. Ocular cicatricial pemphigoid. Ophthalmology. 1981;88:95–100.PubMedCrossRefPubMedCentralGoogle Scholar
  151. Mortazavi H, Khatami A, Seyedin Z, Vasheghani Farahani I, Daneshpazhooh M. Salivary desmoglein enzyme-linked immunosorbent assay for diagnosis of pemphigus vulgaris: a noninvasive alternative test to serum assessment. Biomed Res Int. 2015;2015: 698310.PubMedPubMedCentralCrossRefGoogle Scholar
  152. Murakami H, Nishioka S, Setterfield J, Bhogal BS, Black MM, et al. Analysis of antigens targeted by circulating IgG and IgA autoantibodies in 50 patients with cicatricial pemphigoid. J Dermatol Sci. 1998;17: 39–44.PubMedCrossRefPubMedCentralGoogle Scholar
  153. Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on definitions of disease, end points and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58:1043–6.PubMedPubMedCentralCrossRefGoogle Scholar
  154. Murrell DF, et al. Definitions and outcome measures for mucous membrane pemphigoid (MMP): recommendations of a panel of experts. JAAD. 2015;72(1):168–74.PubMedCrossRefPubMedCentralGoogle Scholar
  155. Nguyen VT, Ndoye A, Shultz LD, Pittelkow MR, Grando SA. Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris-like lesions. J Clin Invest. 2000;106(12): 1467–79.PubMedPubMedCentralCrossRefGoogle Scholar
  156. Nogueira PA, Carneiro S, Ramos-e-Silva M. Oral lichen planus: an update on its pathogenesis. Int J Dermatol. 2015;54:1005–10.PubMedCrossRefPubMedCentralGoogle Scholar
  157. Ohzono A, Sogame R, Li X, et al. Clinical and immunological findings in 104 cases of paraneoplastic pemphigus. Br J Dermatol. 2015;173:1447.PubMedCrossRefPubMedCentralGoogle Scholar
  158. Ormond M, McParland H, Donaldson ANA, Andiappan M, Cook RJ, Escudier M, Hullah E, Higham J, McMillan R, Taylor J, Shirlaw PJ, Challacombe SJ, Setterfield JF. An Oral Disease Severity Score (ODSS) validated for use in oral pemphigus vulgaris. Br J Dermatol. 2018 [Epub ahead of print].Google Scholar
  159. Otten JV, Hashimoto T, Hertl M, Payne AS, Sitaru C. Molecular diagnosis in autoimmune skin blistering conditions. Curr Mol Med. 2014;14:69–95.PubMedPubMedCentralCrossRefGoogle Scholar
  160. Oyama N, Setterfield JF, Powell AM, Sakuma-Oyama Y, Albert S, Bhogal BS, Vaughan RW, Kaneko F, Challacombe SJ, Black MM. Bullous Pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity. Br J Dermatol. 2006;154:90–8.PubMedCrossRefGoogle Scholar
  161. Park HJ, Young JK, Dong HK, Junho K, Park KH, Park J-W, Lee J-H. HLA allele frequencies in 5802 Koreans: varied allele types associated with SJS/TEN according to culprit drugs. Yonsei Med J. 2016;57(1): 118–26.PubMedCrossRefPubMedCentralGoogle Scholar
  162. Proby CM, Ota T, Suzuki H, Koyasu S, Gamou S, Shimizu N, Wahl JK, Wheelock MJ, Nishikawa T, Amagai M. Development of chimeric molecules for recognition and targeting of antigen-specific B cells in pemphigus vulgaris. Br J Dermatol. 2000;142(2): 321–30.PubMedCrossRefPubMedCentralGoogle Scholar
  163. Ran NA, Payne AS. Rituximab therapy in pemphigus and other autoantibody-mediated diseases. F1000Res. 2017;6:83.PubMedPubMedCentralCrossRefGoogle Scholar
  164. Reeves GMB, Lloyd M, Rajlawat BP, et al. Ocular and oral grading of mucous membrane pemphigoid. Graefes Arch Clin Exp Ophthalmol. 2012;250:611–8.PubMedCrossRefPubMedCentralGoogle Scholar
  165. Rogers RS 3rd. Dapsone and sulfapyridine therapy of pemphigoid diseases. Australas J Dermatol. 1986;27:58–63.PubMedCrossRefPubMedCentralGoogle Scholar
  166. Roopashree MR, Gondhalekar RV, Shashikanth MC, George J, Thippeswamy SH, Shukla A. Pathogenesis of oral lichen planus–a review. J Oral Pathol Med. 2010;39:729–34.PubMedCrossRefPubMedCentralGoogle Scholar
  167. Rötzer V, Hartlieb E, Vielmuth F, Gliem M, Spindler V, Waschke J. E-cadherin and Src associate with extradesmosomal Dsg3 and modulate desmosome assembly and adhesion. Cell Mol Life Sci. 2015;72(24): 4885–97.PubMedCrossRefPubMedCentralGoogle Scholar
  168. Roujeau JC, Charron D. HLA class II polymorphism contributes to specify desmoglein derived peptides in pemphigus vulgaris and pemphigus foliaceus. J Autoimmun. 2000;15:67–73.PubMedCrossRefPubMedCentralGoogle Scholar
  169. Sadik CD, Bischof J, van Beek N, Benoit S, Sárdy M, Worm M, Meller S, Gläser R, Zillikens D, Homey B, Setterfield J, Minassian D, Schmidt E, Dart J, MMP study group 2009–2014, Autoimmune Bullous Diseases Study Group, Ibrahim SM. Genome-wide association study identifies GALC as susceptibility gene for mucous membrane pemphigoid. Exp Dermatol. 2017.Google Scholar
  170. Saha M, Bhogal B, Black MM, Cooper D, Vaughan RW, Groves RW. Prognostic factors in pemphigus vulgaris and pemphigus foliaceus. Br J Dermatol. 2014;170(1):116–22.PubMedCrossRefPubMedCentralGoogle Scholar
  171. Sajda T, Hazelton J, Patel M, Seiffert-Sinha K, Steinman L, Robinson W, Haab BB, Sinha AA. Multiplexed autoantigen microarrays identify HLA as a key driver of anti-desmoglein and -non-desmoglein reactivities in pemphigus. Proc Natl Acad Sci USA. 2016;113(7): 1859–64.PubMedCrossRefPubMedCentralGoogle Scholar
  172. Saw VP, Dart JK, Rauz S, Ramsay A, Bunce C, Xing W, Maddison PG, Phillips M. Immunosuppressive therapy for ocular mucous membrane pemphigoid strategies and outcomes. Ophthalmology. 2008;115:253–61.PubMedCrossRefPubMedCentralGoogle Scholar
  173. Schmidt A, Koch PJ. Desmosomes: just cell adhesion or is there more? Cell Adhes Migr. 2007;1(1):28–32.Google Scholar
  174. Schmidt E. Rituximab as first-line treatment of pemphigus. Lancet. 2017;389(10083):1956–8.PubMedCrossRefPubMedCentralGoogle Scholar
  175. Schmidt E, Zillikens D. Modern diagnosis of autoimmune blistering skin diseases. Autoimmun Rev. 2010;10: 84–9.PubMedCrossRefPubMedCentralGoogle Scholar
  176. Schmidt E, Zillikens D. Pemphigoid diseases. Lancet. 2013;381:320–32.PubMedPubMedCentralCrossRefGoogle Scholar
  177. Schmidt E, Skrobek C, Kromminga A, Hashimoto T, Messer G, Bröcker EB, Yancey KB, Zillikens D. Cicatricial pemphigoid: IgA and IgG autoantibodies target epitopes on both intra- and extracellular domains of bullous pemphigoid antigen 180. Br J Dermatol. 2001;145(5):778–83.PubMedCrossRefPubMedCentralGoogle Scholar
  178. Schmidt E, della Torre R, Borradori L. Clinical features and practical diagnosis of bullous pemphigoid. Dermatol Clin 2011;29:427–38PubMedCrossRefPubMedCentralGoogle Scholar
  179. Schmidt E, Spindler V, Eming R, Amagai M, Antonicelli F, et al. Meeting report of the pathogenesis of pemphigus and pemphigoid meeting in Munich, September 2016. J Invest Dermatol. 2017;137(6):1199–203.PubMedCrossRefPubMedCentralGoogle Scholar
  180. Scully C, Bagan J. Oral mucosal diseases: erythema multiforme. Br J Oral Maxillofac Surg. 2008;46(2):90–5.CrossRefGoogle Scholar
  181. Scully CS, Challacombe SJ. Pemphigus vulgaris: update on etiopathogenesis, oral manifestations, and management. Crit Rev Oral Biol Med. 2002;13:397–408.PubMedCrossRefPubMedCentralGoogle Scholar
  182. Seishima M, Iwasaki-Bessho Y, Itoh Y, Nozawa Y, Amagai M, Kitajima Y. Phosphatidylcholine-specific phospholipase C, but not phospholipase D, is involved in pemphigus IgG-induced signal transduction. Arch Dermatol Res. 1999;291(11):606–13.PubMedCrossRefPubMedCentralGoogle Scholar
  183. Setterfield J. Clinicopathological associations in mucous membrane pemphigoid. MD thesis, University of London; 2009.Google Scholar
  184. Setterfield J, Challacombe SJ, Black MM. Oral mucosal pemphigoid. Br J Dermatol 1997;137:825.PubMedCrossRefPubMedCentralGoogle Scholar
  185. Setterfield J, Shirlaw PH, Kerr-Muir M, Bhogal BS, Morgan PR, Challacombe SJ, Tilling K, Black MM. Mucous membrane pemphigoid: a dual circulating antibody response with IgG and IgA signifies a more severe and persistent disease. Br. J Dermatol. 1998;138:602–10.CrossRefGoogle Scholar
  186. Setterfield J, Shirlaw PJ, Bhogal BS, Tilling K, Challacombe SJ, Black MM. Cicatricial pemphigoid: serial titres of circulating IgG and IgA antibasement membrane antibodies correlate with disease activity. Br J Dermatol. 1999a;140(4):645–50.PubMedCrossRefPubMedCentralGoogle Scholar
  187. Setterfield J, Shirlaw PJ, Lazarova Z, Bryant BM, Bhogal BS, Harman K, Challacombe SJ, Black MM. Paraneoplastic cicatricial pemphigoid. Br J Dermatol. 1999b;141:127–31.PubMedCrossRefPubMedCentralGoogle Scholar
  188. Setterfield JF, Black MM, Challacombe SJ. The management of oral lichen planus. Clin Exp Dermatol. 2000;25:176–82.PubMedCrossRefPubMedCentralGoogle Scholar
  189. Setterfield J, Theron J, Welsh K, Vaughan R, Shirlaw P, Wojnarowska F, Challacombe SJ, Black MM. Mucous membrane pemphigoid: HLA DQB1*0301 allele is associated with all clinical sites of involvement and may be linked to anti-basement membrane IgG production. Br J Dermatol. 2001;145:406–14.PubMedCrossRefPubMedCentralGoogle Scholar
  190. Sharma VK, Khandpur S. Evaluation of cyclophosphamide pulse therapy as an adjuvant to oral corticosteroid in the management of pemphigus vulgaris. Clin Exp Dermatol. 2013;38:659–64.PubMedCrossRefPubMedCentralGoogle Scholar
  191. Shirakata Y, Amagai M, Hanakawa Y, Nishikawa T, Hashimoto K. Lack of mucosal involvement in pemphigus foliaceus may be due to low expression of desmoglein 1. J Invest Dermatol. 1998;110:76–8.PubMedCrossRefPubMedCentralGoogle Scholar
  192. Shuttleworth D, Graham-Brown RA, Hutchinson PE, Jolliffe DS. Cicatricial pemphigoid in D-penicillamine treated patients with rheumatoid arthritis–a report of three cases. Clin Exp Dermatol. 1985;10:392–7.PubMedCrossRefPubMedCentralGoogle Scholar
  193. Singh D, Misra N, Agrawal S, Misra P. Angina bullosa haemorrhagica. BMJ Case Rep. 2013;2013:bcr2012008505.PubMedPubMedCentralGoogle Scholar
  194. Stephenson P, Lamey P-J, Scully C, et al. Angina bullosa haemorrhagica: clinical and laboratory features in 30 patients. Oral Surg Oral Med Oral Pathol. 1987;63(5):560–5.PubMedCrossRefPubMedCentralGoogle Scholar
  195. Sultan AS, Villa A, Saavedra AP, Treister NS, Woo SB. Oral mucous membrane pemphigoid and pemphigus vulgaris-a retrospective two-center cohort study. Oral Dis. 2017;23(4):498–504.PubMedCrossRefPubMedCentralGoogle Scholar
  196. Sun Y, Chan RK, Tan SH, Ng PP. Detection and genotyping of human herpes simplex viruses in cutaneous lesions of erythema multiforme by nested PCR. J Med Virol. 2003;71(3):423–8.PubMedCrossRefPubMedCentralGoogle Scholar
  197. Svecova D, Parnicka Z, Pastyrikova L, Urbancek S, Luha J, Buc M. HLA DRB1* and DQB1* alleles are associated with disease severity in patients with pemphigus vulgaris. Int J Dermatol. 2015;54(2):168–73.PubMedCrossRefPubMedCentralGoogle Scholar
  198. Syed S-H, Trinnaman B, Martin S, Major S, Hutchinson J, Magee AI. Molecular interactions between desmosomal cadherins. Biochem J. 2002;362(Pt 2):317–27.PubMedPubMedCentralCrossRefGoogle Scholar
  199. Tauber J, Melamed S, Foster CS. Glaucoma in patients with ocular cicatricial pemphigoid. Ophthalmology. 1989;96:33–7.PubMedCrossRefPubMedCentralGoogle Scholar
  200. Taylor J, McMillan R, Shephard M, Setterfield J, Ahmed R, et al. World workshop on oral medicine VI: a systematic review of the treatment of mucous membrane pemphigoid. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(2):161–71.PubMedCrossRefGoogle Scholar
  201. Tchernev G, Orfanos CE. Antigen mimicry, epitope spreading and the pathogenesis of pemphigus. Tissue Antigens. 2006;68(4):280–6. Review.PubMedCrossRefPubMedCentralGoogle Scholar
  202. Thoma-Uszynski S, Uter W, Schwietzke S, Schuler G, Borradori L, Hertl M. Autoreactive T and B cells from bullous pemphigoid (BP) patients recognize epitopes clustered in distinct regions of BP180 and BP230. J Immunol. 2006;176(3):2015–23.PubMedCrossRefPubMedCentralGoogle Scholar
  203. Toto P, Feliciani C, Amerio P, Suzuki H, Wang B, Shivji GM, Woodley D, Sauder DN. Immune modulation in pemphigus vulgaris: role of CD28 and IL-10. J Immunol. 2000;164(1):522–9.PubMedCrossRefPubMedCentralGoogle Scholar
  204. Taghipour K, et al. Autoimmune and other blistering diseases. Medicine 2009;37(6):291–297.CrossRefGoogle Scholar
  205. Tyagi S, Bhol K, Natarajan K, et al. Ocular cicatricial pemphigoid antigen: partial sequence and biochemical characterization. Proc Natl Acad Sci USA 1996;93:14714–19.CrossRefGoogle Scholar
  206. Uzun S, Durdu M, Akman A, et al. Pemphigus in the Mediterranean region of Turkey: a study of 148 cases. Int J Dermatol. 2006;45:523–8.PubMedCrossRefPubMedCentralGoogle Scholar
  207. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  208. Vodo D, Sarig O, Geller S, Ben-Asher E, et al. Identification of a functional risk variant for pemphigus vulgaris in the ST18 gene. PLoS Genet. 2016;12(5):e1006008.PubMedPubMedCentralCrossRefGoogle Scholar
  209. Von Kries N. Cauistsche Mittheilungen aus der Augenklinik zu Halle: V. Essentielle Schrumpfung der Conjunctiva. Arch Ophthalmol (Berlin). 1878;24:157–8.Google Scholar
  210. Wang HH, Liu CW, Li YC, et al. Efficacy of rituximab for pemphigus: a systematic review and meta-analysis of different regimens. Acta Derm Venereol. 2015;95(8): 928–32.PubMedCrossRefPubMedCentralGoogle Scholar
  211. Wee J, Shirlaw PJ, Challacombe SJ, Setterfield JF. Efficacy of mycophenolate mofetil in severe mucocutaneous lichen planus: a retrospective review of 10 patients. Br J Dermatol. 2012;167:36–43.CrossRefGoogle Scholar
  212. Wetter DA, Davis MD. Recurrent erythema multiforme: clinical characteristics, etiologic associations, and treatment in a series of 48 patients at Mayo Clinic, 2000 to 2007. J Am Acad Dermatol. 2010;62(1):45–53.PubMedCrossRefPubMedCentralGoogle Scholar
  213. Wichmann J. Ideen zur Diagnostik: Beobachtenden Aerzten Mitgetheilet. Hanover: Helwing; 1794.Google Scholar
  214. Wieczorek M, Czernik A. Paraneoplastic pemphigus: a short review. Clin Cosmet Investig Dermatol. 2016;9:291–5.PubMedPubMedCentralCrossRefGoogle Scholar
  215. Williams HC, Wojnarowska F, Kirtschig G, Mason J, et al. And clinical trials network BLISTER study group. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Lancet. 2017;389(10079):1630–8.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  217. Yong AA, Tey HL. Paraneoplastic pemphigus. Australas J Dermatol. 2013;54(4):241–50. Review.PubMedCrossRefPubMedCentralGoogle Scholar
  218. You C, Lamba N, Lasave AF, Ma L, Diaz MH, Foster CS. Rituximab in the treatment of ocular cicatricial pemphigoid: a retrospective cohort study. Graefes Arch Clin Exp Ophthalmol. 2017;255(6):1221–8.PubMedCrossRefPubMedCentralGoogle Scholar
  219. Yunis JJ, Mobini N, Yunis EJ, Alper CA, Deulofeut R, Rodriguez A, Foster CS, Marcus-Bagley D, Good RA, Ahmed AR. Common major histocompatibility complex class II markers in clinical variants of cicatricial pemphigoid. Proc Natl Acad Sci USA. 1994;91: 7747–51.PubMedCrossRefPubMedCentralGoogle Scholar
  220. Zhou XJ, Sugerman PB, Savage NW, Walsh LJ, Seymour GJ. Intra-epithelial CD8+ T cells and basement membrane disruption in oral lichen planus. J Oral Pathol Med. 2002;31:23–7.PubMedCrossRefGoogle Scholar
  221. Zillikens D, Wever S, Roth A, Weidenthaler-Barth B, Hashimoto T, Brocker EB. Incidence of autoimmune subepidermal blistering dermatoses in a region of Central Germany. Arch Dermatol. 1995;131:957–8.PubMedCrossRefPubMedCentralGoogle Scholar
  222. Zillikens D, Kawahara Y, Ishiko A, Shimizu H, Mayer J, Rank CV, Liu Z, Giudice GJ, Tran HH, Marinkovich MP, Brocker EB, Hashimoto T. A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen of the basement membrane zone. J Invest Dermatol. 1996;106:1333–8.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Stephen J. Challacombe
    • 1
    • 3
    Email author
  • Jane F. Setterfield
    • 1
    • 2
    • 3
  1. 1.Department of Oral MedicineKing’s College LondonLondonUK
  2. 2.Department of DermatologyKing’s College LondonLondonUK
  3. 3.Guys and St Thomas’ Hospital NHS Foundation TrustLondonUK

Section editors and affiliations

  • Camile S. Farah
    • 1
  1. 1.UWA Dental SchoolUniversity of Western AustraliaPerthAustralia

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