Pemphigus Disease Activity Measurements: Pemphigus Disease Area Index, Autoimmune Bullous Skin Disorder Intensity Score, and Pemphigus Vulgaris Activity Score

  • Ziba RahbarEmail author
Living reference work entry


Pemphigus is a group of rare skin condition with blisters in the skin and mucosa that are associated with autoantibodies against intercellular adhesion molecules. Effective therapies can improve its devastating morbidities and mortality. Using a uniform, consensus-based and validated disease activity measure is essential to multicenter clinical trials for new therapies, meta-analysis of smaller studies, and evidence-based practice. However, above 116 outcome measures exist to assess pemphigus disease activity.

Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), and Pemphigus Vulgaris Activity Score (PVAS) are the most comprehensively validated measures. The consensus-based standards for the selection of health status measurement instruments (COSMIN) study recommends investigation for the measurement properties of reliability, validity, and responsiveness. Here, PDAI, ABSIS, and PVAS are presented and compared based on their measurement properties including reliability, feasibility, and correlation with anti-desmoglein using one large prospective study (n = 100) comparing all three measures. Also, a review of additional properties including validity, responsiveness, and severity cutoffs is included using updated studies.

PDAI has the greatest reliability and is least affected by variability in rater’s pemphigus expertise. All three pemphigus measures have acceptable convergent validity with Physician Global Assessment, but PVAS seems to have the greatest value. PVAS is the fastest and simplest score to complete. Responsiveness studies may be needed for comprehensive validation. There are inconsistencies in severity cutoffs. Recently, PDAI, as the internationally accepted pemphigus disease measure, has been increasingly used in different studies around the world.


Pemphigus Autoimmune Blistering Bullous Disease activity Disease damage Measure Score Severity PDAI 


  1. Abasq C, Mouquet H, Gilbert D, Tron F, Grassi V, Musette P, Joly P. ELISA testing of anti-desmoglein 1 and 3 antibodies in the management of pemphigus. Arch Dermatol. 2009;145:529–35. Scholar
  2. Amagai M, Tsunoda K, Zillikens D, Nagai T, Nishikawa T. The clinical phenotype of pemphigus is defined by the anti-desmoglein autoantibody profile. J Am Acad Dermatol. 1999;40:167–70.CrossRefGoogle Scholar
  3. Boulard C, Duvert Lehembre S, Picard-Dahan C, Kern JS, Zambruno G, Feliciani C, Marinovic B, Vabres P, Borradori L, Prost-Squarcioni C, Labeille B, Richard MA, Ingen-Housz-Oro S, Houivet E, Werth VP, Murrell DF, Hertl M, Benichou J, Joly P, International Pemphigus Study Group. Calculation of cut-off values based on the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI) pemphigus scoring systems for defining moderate, significant and extensive types of pemphigus. Br J Dermatol. 2016;175:142–9. Scholar
  4. Chams-Davatchi C, Mortazavizadeh A, Daneshpazhooh M, Davatchi F, Balighi K, Esmaili N, Akhyani M, Hallaji Z, Seirafi H, Mortazavi H. Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris. J Eur Acad Dermatol Venereol. 2012;27(10):1285–92. Scholar
  5. Chams-Davatchi C, Rahbar Z, Daneshpazhooh M, Mortazavizadeh SMA, Akhyani M, Esmaili N, Balighi K. Pemphigus vulgaris activity score and assessment of convergent validity. Acta Med Iran. 2013;51:224–30.PubMedGoogle Scholar
  6. Daneshpazhooh M, Chams-Davatchi C, Khamesipour A, Mansoori P, Taheri A, Firooz A, Mortazavi H, Esmaili N, Dowlati Y. Desmoglein 1 and 3 enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris: correlation with phenotype, severity, and disease activity. J Eur Acad Dermatol Venereol. 2007;21:1319–24.CrossRefGoogle Scholar
  7. Hanna S, Kim M, Murrell DF. Validation studies of outcome measures in pemphigus. Int J Womens Dermatol. 2016;2:128–39. Scholar
  8. 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.CrossRefGoogle Scholar
  9. Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, Houivet E, Calbo S, Caillot F, Golinski ML, Labeille B, Picard-Dahan C, Paul C, Richard M-A, Bouaziz JD, Duvert-Lehembre S, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Delaporte E, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D’Incan M, Bedane C, Bénéton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Vermeulin T, Benichou J, Musette P, French study group on autoimmune bullous skin diseases. 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 Lond Engl. 2017;389:2031–40. Scholar
  10. Kamiya K, Aoyama Y, Shirafuji Y, Hamada T, Morizane S, Fujii K, Hisata K, Iwatsuki K. Detection of antibodies against the non-calcium-dependent epitopes of desmoglein 3 in pemphigus vulgaris and their pathogenic significance. Br J Dermatol. 2012;167:252–61. Scholar
  11. Kamiya K, Aoyama Y, Shirafuji Y, Hamada T, Morizane S, Fujii K, Iwatsuki K. A higher correlation of the antibody activities against the calcium-dependent epitopes of desmoglein 3 quantified by ethylenediaminetetraacetic acid-treated enzyme-linked immunosorbent assay with clinical disease activities of pemphigus vulgaris. J Dermatol Sci. 2013;70:190–5. Scholar
  12. Kwon EJ, Yamagami J, Nishikawa T, Amagai M. Anti-desmoglein IgG autoantibodies in patients with pemphigus in remission. J Eur Acad Dermatol Venereol. 2008;22:1070–5. Scholar
  13. Martin LK, Werth VP, Villaneuva EV, Murrell DF. A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol. 2011;64:903–8. Scholar
  14. Mokkink LB, Terwee CB, Patrick DL, Alonso J, Stratford PW, Knol DL, Bouter LM, de Vet HCW. The COSMIN checklist for assessing the methodological quality of studies on measurement properties of health status measurement instruments: an international Delphi study. Qual Life Res. 2010;19:539–49. Scholar
  15. Murrell DF, Dick S, Ahmed AR, Amagai M, Barnadas MA, Borradori L, Bystryn J-C, Cianchini G, Diaz L, Fivenson D, Hall R, Harman KE, Hashimoto T, Hertl M, Hunzelmann N, Iranzo P, Joly P, Jonkman MF, Kitajima Y, Korman NJ, Martin LK, Mimouni D, Pandya AG, Payne AS, Rubenstein D, Shimizu H, Sinha AA, Sirois D, Zillikens D, Werth VP. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58:1043–6. Scholar
  16. Murrell DF, Amagai M, Werth VP. Scoring systems for blistering diseases in practice. J Am Acad Dermatol. 2014;150(3):245.CrossRefGoogle Scholar
  17. Patsatsi A, Kyriakou A, Giannakou A, Pavlitou-Tsiontsi A, Lambropoulos A, Sotiriadis D. Clinical significance of anti-desmoglein-1 and -3 circulating autoantibodies in pemphigus patients measured by area index and intensity score. Acta Derm Venereol. 2014;94:203–6. Scholar
  18. Pfutze M, Niedermeier A, Hertl M, Eming R. Introducing a novel Autoimmune Bullous Skin Disorder Intensity core (ABSIS) in pemphigus. Eur J Dermatol. 2007;17:4–11. Scholar
  19. Rahbar Z, Daneshpazhooh M, Mirshams-Shahshahani M, Esmaili N, Heidari K, Aghazadeh N, Hejazi P, Ghajarzadeh M, Chams-Davatchi C. Pemphigus disease activity measurements: pemphigus disease area index, autoimmune bullous skin disorder intensity score, and pemphigus vulgaris activity score. JAMA Dermatol. 2014;150:266–72. Scholar
  20. Rosenbach M, Murrell DF, Bystryn JC, Dulay S, Dick S, Fakharzadeh S, Hall R, Korman NJ, Lin J, Okawa J, Pandya AG, Payne AS, Rose M, Rubenstein D, Woodley D, Vittorio C, Werth BB, Williams EA, Taylor L, Troxel AB, Werth VP. Reliability and convergent validity of two outcome instruments for pemphigus. J Invest Dermatol. 2009;129:2404–10. Scholar
  21. Shimizu T, Takebayashi T, Sato Y, Niizeki H, Aoyama Y, Kitajima Y, Iwatsuki K, Hashimoto T, Yamagami J, Werth VP, Amagai M, Tanikawa A. Grading criteria for disease severity by pemphigus disease area index. J Dermatol. 2014;41:969–73. Scholar
  22. Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull. 1979;86:420–8.CrossRefGoogle Scholar
  23. Sison-Fonacier L, Bystryn JC. Regional variations in antigenic properties of skin. A possible cause for disease-specific distribution of skin lesions. J Exp Med. 1986;164:2125–30.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Autoimmune Bullous Diseases Research Center, Department of DermatologyRazi Hospital, Tehran University of Medical SciencesTehranIran
  2. 2.Dermatology DepartmentStanford University School of MedicinePalo AltoUSA

Personalised recommendations