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Oral Vesicular and Bullous Lesions

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Contemporary Oral Medicine

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Abstract

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.

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References

  • 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.

    Article  PubMed  Google Scholar 

  • Aboobaker J, Morar N, Ramdial PK, Hammond MG. Pemphigus in South Africa. Int J Dermatol. 2001;40:115–9.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Ahmed AR, Hombal SM. Cicatricial pemphigoid. Int J Dermatol. 1986;25:90–6.

    Article  PubMed  Google Scholar 

  • Ahmed AR, Shetty SA. Comprehensive analysis of treatment outcomes in patients with pemphigus vulgaris treated with rituximab. Autoimmun Rev. 2015;14(4): 323–31.

    Article  PubMed  Google Scholar 

  • Ahmed AR, Kurgis BS, Rogers IR. Cicatricial pemphigoid. J Am Acad Dermatol. 1991;24:987–1001.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Allen CM, Camisa C. Paraneoplastic pemphigus: a review of the literature. Oral Dis. 2000;6:208–14.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Amagai M. Towards a better understanding of pemphigus autoimmunity. Br J Dermatol. 2000;143:237–8.

    Article  PubMed  Google Scholar 

  • Amagai M, Stanley JR. Desmoglein as a target in skin disease and beyond. J Invest Dermatol. 2012;132(3 pt 2):776–84.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • Anhalt GJ. Paraneoplastic pemphigus. Adv Dermatol. 1997;12:77.

    PubMed  Google Scholar 

  • Anhalt GJ. Paraneoplastic pemphigus. J Investig Dermatol Symp Proc. 2004;9:29–33.

    Article  PubMed  Google Scholar 

  • Anhalt GJ, Kim SC, et al. Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med. 1990;323:1729–35.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Ayangco L, Rogers RS 3rd. Oral manifestations of erythema multiforme. Dermatol Clin. 2003;21(1): 195–205.

    Article  PubMed  Google Scholar 

  • Barnados MA. Dermatitis herpetiformis: a review of direct immunofluorescence findings. Am J Dermatopathol. 2016;38(4):283–8.

    Article  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Bean SF, Waisman M, Michel B, Thomas CI, Knox JM, Levine M. Cicatricial pemphigoid. Immunofluorescent studies. Arch Dermatol. 1972;106:195–9.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Borradori L, Sonnenberg A. Structure and function of hemidesmosomes: more than simple adhesion complexes. J Invest Dermatol. 1999;112:411–8.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Bunker CB. Male genital skin disease. Edinburgh: Saunders; 2004.

    Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Buxton RS, Magee AI. Structure and interactions of desmosomal and other cadherins. Semin Cell Biol. 1992;3(3):157–67. Review.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chorzelski TP, Jablonska S. IgA linear dermatosis of childhood (chronic bullous disease of childhood). Br J Dermatol. 1979;101:535–42.

    Article  PubMed  Google Scholar 

  • Civatte A. Le diagnostic des dermatoses bulleuses au laboratoire. Arch Belg Dermatol Syphiligr. 1949;5: 273–5.

    PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dantzig P. Circulating antibodies in cicatricial pemphigoid. Arch Dermatol. 1973;108:264–6.

    Article  PubMed  Google Scholar 

  • Dart JK. The 2016 Bowman lecture conjunctival curses: scarring conjunctivitis 30 years on. Eye (Lond). 2017;31:301–32.

    Article  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Zenzo G, Carrozzo M, Chan LS. Urban legend series: mucous membrane pemphigoid. Oral Dis. 2014;20(1): 35–54.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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. 2017

    Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ellebrecht CT, Payne AS. Setting the target for pemphigus vulgaris therapy. JCI Insight. 2017;2(5):e92021. Review.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Farthing P, Bagan JV, Scully C. Mucosal disease series. Number IV. Erythema multiforme. Oral Dis. 2005;11(5):261–7.

    Article  PubMed  Google Scholar 

  • Fortuna G, Marinkovich P. Linear immunoglobulin A bullous dermatosis. Clin Dermatol. 2012;30:38–50.

    Article  PubMed  Google Scholar 

  • Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc. 1986;84:527–663.

    PubMed  PubMed Central  Google Scholar 

  • Gallagher G, Shklar G. Oral involvement in mucous membrane pemphigoid. Clin Dermatol. 1987;5:18–27.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • Gniadecki R. Desmoglein autoimmunity in the pathogenesis of pemphigus. Autoimmunity. 2006;39(7):541–7. Review.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Hammers CM, Stanley JR. Mechanisms of disease: pemphigus and bullous pemphigoid. Annu Rev Pathol. 2016;11:175–97.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Hardy KM, Perry HO, Pingree GC, Kirby TJ Jr. Benign mucous membrane pemphigoid. Arch Dermatol. 1971;104:467–75.

    Article  PubMed  Google Scholar 

  • Harfouch E, Daoud S. Allelic variation in HLA-DRB1* loci in Syrian pemphigus vulgaris patients. Int J Dermatol. 2014;53(12):1460–3.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Hashimoto T. Immunopathology of paraneoplastic pemphigus. Clin Dermatol. 2001;19:675–82.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Herbst A, Bystryn JC. Patterns of remission in pemphigus vulgaris.J Am Acad Dermatol. 2000;42(3):422–7.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Kirtschig G, Murrell D, Wojnarowska F, Khumalo N. Interventions for mucous membrane pemphigoid and epidermolysis bullosa acquisita. Cochrane Database Syst Rev. 2003;(1):CD004056. Review

    Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Korman N. Pemphigus. J Am Acad Dermatol. 1988;18(6):1219–38. Review.

    Google Scholar 

  • Korman N. Pemphigus. J Am Acad Dermatol. 1988;18(6):1219–38. Review. PMID: 3290286.

    Google Scholar 

  • Kowalczyk AP, Green KJ. Structure, function and regulation of desmosomes. Prog Mol Biol Transl Sci. 2013;116:95–118.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Kridin K, Zelber-Sagi S, Bergman R. Pemphigus vulgaris and pemphigus foliaceus: differences in epidemiology and mortality. Acta Derm Venereol. 2017.

    Google Scholar 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Lara-Corrales I, Pope E. Autoimmune blistering diseases in children. Semin Cutan Med Surg. 2010;29(2):85–91.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Lever W. Pemphigus: a histopathologic study. Arch Dermatol. 1951;64:727–53.

    Google Scholar 

  • 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 

  • 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 

  • Liakopoulou A, Rallis E. Bullous lichen planus – a review. J Dermatol Case Rep. 2017;11(1):1–4.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Ludwig RJ. Clinical presentation, pathogenesis, diagnosis, and treatment of epidermolysis bullosa acquisita. ISRN Dermatol. 2013;2013:812029.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Martin LK, Werth V, Villanueva E, et al. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev. 2009;(1):CD006263.

    Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Mehren CR, Gniadecki R. Epidermolysis bullosa acquisita: current diagnosis and therapy. Dermatol Reports. 2011;3(3):e38.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Mondino BJ, Brown SI. Ocular cicatricial pemphigoid. Ophthalmology. 1981;88:95–100.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nogueira PA, Carneiro S, Ramos-e-Silva M. Oral lichen planus: an update on its pathogenesis. Int J Dermatol. 2015;54:1005–10.

    Article  PubMed  Google Scholar 

  • Ohzono A, Sogame R, Li X, et al. Clinical and immunological findings in 104 cases of paraneoplastic pemphigus. Br J Dermatol. 2015;173:1447.

    Article  PubMed  Google Scholar 

  • 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 

  • Otten JV, Hashimoto T, Hertl M, Payne AS, Sitaru C. Molecular diagnosis in autoimmune skin blistering conditions. Curr Mol Med. 2014;14:69–95.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Ran NA, Payne AS. Rituximab therapy in pemphigus and other autoantibody-mediated diseases. F1000Res. 2017;6:83.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Rogers RS 3rd. Dapsone and sulfapyridine therapy of pemphigoid diseases. Australas J Dermatol. 1986;27:58–63.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Schmidt A, Koch PJ. Desmosomes: just cell adhesion or is there more? Cell Adhes Migr. 2007;1(1):28–32.

    Google Scholar 

  • Schmidt E. Rituximab as first-line treatment of pemphigus. Lancet. 2017;389(10083):1956–8.

    Article  PubMed  Google Scholar 

  • Schmidt E, Zillikens D. Modern diagnosis of autoimmune blistering skin diseases. Autoimmun Rev. 2010;10: 84–9.

    Article  PubMed  Google Scholar 

  • Schmidt E, Zillikens D. Pemphigoid diseases. Lancet. 2013;381:320–32.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Schmidt E, della Torre R, Borradori L. Clinical features and practical diagnosis of bullous pemphigoid. Dermatol Clin 2011;29:427–38

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Scully C, Bagan J. Oral mucosal diseases: erythema multiforme. Br J Oral Maxillofac Surg. 2008;46(2):90–5.

    Article  PubMed  Google Scholar 

  • Scully CS, Challacombe SJ. Pemphigus vulgaris: update on etiopathogenesis, oral manifestations, and management. Crit Rev Oral Biol Med. 2002;13:397–408.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Setterfield J. Clinicopathological associations in mucous membrane pemphigoid. MD thesis, University of London; 2009.

    Google Scholar 

  • Setterfield J, Challacombe SJ, Black MM. Oral mucosal pemphigoid. Br J Dermatol 1997;137:825.

    Article  PubMed  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Setterfield JF, Black MM, Challacombe SJ. The management of oral lichen planus. Clin Exp Dermatol. 2000;25:176–82.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Singh D, Misra N, Agrawal S, Misra P. Angina bullosa haemorrhagica. BMJ Case Rep. 2013;2013:bcr2012008505.

    PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tauber J, Melamed S, Foster CS. Glaucoma in patients with ocular cicatricial pemphigoid. Ophthalmology. 1989;96:33–7.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Tchernev G, Orfanos CE. Antigen mimicry, epitope spreading and the pathogenesis of pemphigus. Tissue Antigens. 2006;68(4):280–6. Review.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Taghipour K, et al. Autoimmune and other blistering diseases. Medicine 2009;37(6):291–297.

    Article  Google Scholar 

  • 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.

    Article  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Von Kries N. Cauistsche Mittheilungen aus der Augenklinik zu Halle: V. Essentielle Schrumpfung der Conjunctiva. Arch Ophthalmol (Berlin). 1878;24:157–8.

    Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Wichmann J. Ideen zur Diagnostik: Beobachtenden Aerzten Mitgetheilet. Hanover: Helwing; 1794.

    Google Scholar 

  • Wieczorek M, Czernik A. Paraneoplastic pemphigus: a short review. Clin Cosmet Investig Dermatol. 2016;9:291–5.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Yong AA, Tey HL. Paraneoplastic pemphigus. Australas J Dermatol. 2013;54(4):241–50. Review.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oral Medicine, King’s College London, London, UK

    Stephen J. Challacombe & Jane F. Setterfield

  2. Department of Dermatology, King’s College London, London, UK

    Jane F. Setterfield

  3. Guys and St Thomas’ Hospital NHS Foundation Trust, London, UK

    Stephen J. Challacombe & Jane F. Setterfield

Authors
  1. Stephen J. Challacombe
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  2. Jane F. Setterfield
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Corresponding author

Correspondence to Stephen J. Challacombe .

Editor information

Editors and Affiliations

  1. UWA Dental School and Oral Health Centre of Western Australia, Faculty of Health and Medical Sciences University of Western Australia, Perth, WA, Australia

    Camile S. Farah

  2. UWA Dental School and Oral Health Centre of Western Australia, Faculty of Health and Medical Sciences University of Western Australia, Perth, WA, Australia

    Ramesh Balasubramaniam

  3. Oral Anatomy, Medicine, and Surgery Section Melbourne Dental School, Faculty of Medicine, Dentistry and Health Sciences The University of Melbourne, Carlton, VIC, Australia

    Michael J. McCullough

Section Editor information

  1. UWA Dental School, University of Western Australia, Perth, WA, Australia

    Camile S. Farah

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Challacombe, S.J., Setterfield, J.F. (2019). Oral Vesicular and Bullous Lesions. In: Farah, C., Balasubramaniam, R., McCullough, M. (eds) Contemporary Oral Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-72303-7_13

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  • DOI: https://doi.org/10.1007/978-3-319-72303-7_13

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