Autoimmune Blistering Disease: Outcome Measures

  • Grace G. Bak
  • Dédée F. MurrellEmail author
Living reference work entry


Autoimmune blistering diseases (AIBD) represent a heterogeneous group of chronic, debilitating diseases. It has been shown that both active disease and past damage from AIBD can cause significant morbidity and negatively impact on the patient’s function. It is therefore important that the outcome measures of AIBD used in practice are objective, reliable, and specific. The development and validation of outcome measures specific to AIBD have been a significant point of focus in recent years. Spanning over a decade, the efforts and collaborations of various groups internationally have culminated in the development of several measures for disease severity and quality of life in AIBD. These include instruments such as the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), Pemphigus Disease Area Index (PDAI), and Bullous Pemphigoid Disease Area Index (BPDAI), which have all shown to be promising tools in the assessment of disease severity and treatment response. Additionally, the important tools to measure changes in the patient’s quality of life (QOL) due to disease burden and treatment have been increasingly recognized. This has resulted in the development of the Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires. It is hoped that a combination of these outcome measures will be more widely utilized in clinical trials and routine practice, shifting the focus of AIBD care from clinical endpoints to patient-centered outcomes.


Pemphigus, Pemphigoid, Outcome measures, Severity, ABSIS, PDAI, BPDAI, MMPDAI, ABQOL, TABQOL 


  1. Acosta E, Gilkes JJ, Ivanyi L. Relationship between the serum autoantibody titers and the clinical activity of pemphigus vulgaris. Oral Surg Oral Med Oral Pathol. 1985;60(6):611–4.PubMedCrossRefGoogle Scholar
  2. Agarwal M, Walia R, Kochhar AM, Chander R. Pemphigus area and activity score (PAAS) – a novel clinical scoring method for monitoring of pemphigus vulgaris patients. Int J Dermatol. 1998;37(2):158–60.PubMedGoogle Scholar
  3. Chams-Davatchi C, Rahbar Z, Daneshpazhooh M, Mortazavizadeh SM, Akhyani M, Esmaili N, Balighi K. Pemphigus vulgaris activity score and assessment of convergent validity. Acta Med Iran. 2013;51(4):224–30.PubMedGoogle Scholar
  4. Cheng SW, Kobayashi M, Kinoshita-Kuroda K, Tanikawa A, Amagai M, Nishikawa T. Monitoring disease activity in pemphigus with enzyme-linked immunosorbent assay using recombinant desmogleins 1 and 3. Br J Dermatol. 2002;147(2):261–5.PubMedCrossRefGoogle Scholar
  5. Chren M-M. The Skindex instruments to measure the effects of skin disease on quality of life. Dermatol Clin. 2012;30(2):231–6. Scholar
  6. Cianchini G, Paradisi A, Murrell DF. Quality of life in autoimmune blistering diseases. In: Murrell DF, editor. Blistering diseases: clinical features, pathogenesis, treatment. Berlin/Heidelberg: Springer; 2015. p. 623–31.Google Scholar
  7. Cook CE. Clinimetrics corner: the minimal clinically important change score (MCID): a necessary pretense. J Man Manip Ther. 2008;16(4):E82–3.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Daniel BS, Hertl M, Werth VP, Eming R, Murrell DF. Severity score indexes for blistering diseases. Clin Dermatol. 2012;30(1):108–13. Scholar
  9. Finlay AY, Khan GK. Dermatology life quality index (DLQI) – a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210–6.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Fitzpatrick RE, Newcomer VD. The correlation of disease activity and antibody titers in pemphigus. Arch Dermatol. 1980;116(3):285–90.PubMedCrossRefGoogle Scholar
  11. Gaines E, Werth VP. Development of outcome measures for autoimmune dermatoses. Arch Dermatol Res. 2008;300(1):3–9. Scholar
  12. Ghodsi SZ, Chams-Davatchi C, Daneshpazhooh M, Valikhani M, Esmaili N. Quality of life and psychological status of patients with pemphigus vulgaris using dermatology life quality index and general health questionnaires. J Dermatol. 2012;39(2):141–4. Scholar
  13. Hanna S, Kim M, Murrell DF. Validation studies of outcome measures in pemphigus. Int J Women’s Dermat. 2016;2(4):128–39. Scholar
  14. 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(4):775–80.PubMedCrossRefGoogle Scholar
  15. Herbst A, Bystryn JC. Patterns of remission in pemphigus vulgaris. J Am Acad Dermatol. 2000;42(3):422–7.PubMedCrossRefGoogle Scholar
  16. Herrero-Gonzalez JE, Iranzo P, Benitez D, Lozano F, Herrero C, Mascaro JM Jr. Correlation of immunological profile with phenotype and disease outcome in pemphigus. Acta Derm Venereol. 2010;90(4):401–5. Scholar
  17. Hertl M. Autoimmune diseases of the skin: pathogenesis, diagnosis, management. Vienna: Springer; 2013.Google Scholar
  18. Ikeda S, Imamura S, Hashimoto I, Morioka S, Sakuma M, Ogawa H. History of the establishment and revision of diagnostic criteria, severity index and therapeutic guidelines for pemphigus in Japan. Arch Dermatol Res. 2003;295(Suppl 1):S12–6. Scholar
  19. Iwata Y, Komura K, Kodera M, Usuda T, Yokoyama Y, Hara T, … Sato S. Correlation of IgE autoantibody to BP180 with a severe form of bullous pemphigoid. Arch Dermatol. 2008;144(1):41–8.
  20. Kalinska-Bienias A, Jakubowska B, Kowalewski C, Murrell DF, Wozniak K. Measuring of quality of life in autoimmune blistering disorders in Poland. Validation of disease – specific autoimmune bullous disease quality of life (ABQOL) and the treatment autoimmune bullous disease quality of life (TABQOL) questionnaires. Adv Med Sci. 2017;62(1):92–6. Scholar
  21. Koller M, Lorenz W. Quality of life: a deconstruction for clinicians. J R Soc Med. 2002;95(10): 481–8.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Levy-Sitbon C, Barbe C, Plee J, Goeldel AL, Antonicelli F, Reguiai Z, … Bernard P. Assessment of bullous pemphigoid disease area index during treatment: a prospective study of 30 patients. Dermatology. 2014;229(2):116–22. Scholar
  23. Liu Z, Diaz LA, Troy JL, Taylor AF, Emery DJ, Fairley JA, Giudice GJ. A passive transfer model of the organ-specific autoimmune disease, bullous pemphigoid, using antibodies generated against the hemidesmosomal antigen, BP180. J Clin Invest. 1993;92(5):2480–8. Scholar
  24. Mahajan VK, Sharma NL, Sharma RC, Garg G. Twelve-year clinico-therapeutic experience in pemphigus: a retrospective study of 54 cases. Int J Dermatol. 2005;44(10):821–7. Scholar
  25. Martin L, Murrell DF. Measuring the immeasurable: a systematic review of outcome measures in pemphigus. Aust J Dermatol. 2006;47:A32–3.CrossRefGoogle Scholar
  26. Mayrshofer F, Hertl M, Sinkgraven R, Sticherling M, Pfeiffer C, Zillikens D, … Rzany Fur Die Deutschebsd-Studiengruppe, B. Significant decrease in quality of life in patients with pemphigus vulgaris. Results from the German bullous skin disease (BSD) study group. J Dtsch Dermatol Ges. 2005;3(6):431–5. Scholar
  27. Montazeri A, Harirchi AM, Shariati M, Garmaroudi G, Ebadi M, Fateh A. The 12-item general health questionnaire (GHQ-12): translation and validation study of the Iranian version. Health Qual Life Outcomes. 2003;1:66. Scholar
  28. Murrell, DF, Dick S, Ahmed AR, Amagai M, Barnadas MA, Borradori L, … Werth VP. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58(6):1043–6. Scholar
  29. Murrell DF, Daniel BS, Joly P, Borradori L, Amagai M, Hashimoto T, … Werth VP. Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts. J Am Acad Dermatol. 2012;66(3):479–85. Scholar
  30. Murrell DF, Marinovic B, Caux F, Prost C, Ahmed R, Wozniak K, … Werth VP. Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts. J Am Acad Dermatol. 2015;72(1):168–74. Scholar
  31. Patsatsi A, Kyriakou A, Pavlitou-Tsiontsi A, Giannakou A, Sotiriadis D. Association of autoantibodies to BP180 with disease activity in Greek patients with bullous pemphigoid. Clin Dev Immunol. 2012;2012:854795. Scholar
  32. Penha MÁ, Farat JG, Miot HA, Barraviera SRCS. Quality of life index in autoimmune bullous dermatosis patients. An Bras Dermatol. 2015;90(2):190–4. Scholar
  33. Pfutze M, Niedermeier A, Hertl M, Eming R. Introducing a novel autoimmune bullous skin disorder intensity score (ABSIS) in pemphigus. Eur J Dermatol. 2007;17(1):4–11. Scholar
  34. Rahbar Z, Daneshpazhooh M, Mirshams-Shahshahani M, Esmaili N, Heidari K, Aghazadeh N, … 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(3):266–72. Scholar
  35. Rosenbach M, Murrell DF, Bystryn JC, Dulay S, Dick S, Fakharzadeh S, … Werth VP. Reliability and convergent validity of two outcome instruments for pemphigus. J Invest Dermatol. 2009;129(10):2404–10. Scholar
  36. Ryan TJ. Disability in dermatology. Br J Hosp Med. 1991;46(1):33–6.PubMedGoogle Scholar
  37. Saraswat A, Bhushan K, India C. A new grading system for oral pemphigus. Int J Dermatol. 2003;42(5):413–4.PubMedCrossRefGoogle Scholar
  38. Schmidt E, Obe K, Brocker EB, Zillikens D. Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid. Arch Dermatol. 2000;136(2):174–8.PubMedCrossRefGoogle Scholar
  39. Schmidt E, Dahnrich C, Rosemann A, Probst C, Komorowski L, Saschenbrecker S, … Zillikens D. Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients. Exp Dermatol. 2010;19(5):458–63. Scholar
  40. Sebaratnam DF, Hanna AM, Chee SN, Frew JW, Venugopal SS, Daniel BS, … Murrell DF. Development of a quality-of-life instrument for autoimmune bullous disease: the autoimmune bullous disease quality of life questionnaire. JAMA Dermatol. 2013;149(10): 1186–91. Scholar
  41. Sebaratnam DF, Hertl M, Werth VP, Murrell D. Extent measures in autoimmune bullous disease. In: Murrell DF, editor. Blistering diseases: clinical features, pathogenesis, treatment. Berlin/Heidelberg: Springer Berlin Heidelberg; 2015a. p. 633–42.Google Scholar
  42. Sebaratnam DF, Okawa J, Payne A, Murrell DF, Werth VP. Reliability of the autoimmune bullous disease quality of life (ABQOL) questionnaire in the USA. Qual Life Res. 2015b;24(9): 2257–60. Scholar
  43. 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(6):2125–30.PubMedCrossRefGoogle Scholar
  44. Souza SR, Azulay-Abulafia L, Nascimento LV. Validation of the commitment index of skin and mucous membranes in pemphigus vulgaris for the clinical evaluation of patients with pemphigus vulgaris. An Bras Dermatol. 2011;86(2):284–91.PubMedCrossRefGoogle Scholar
  45. Tjokrowidjaja A, Daniel BS, Frew JW, Sebaratnam DF, Hanna AM, Chee S, … Murrell DF. The development and validation of the treatment of autoimmune bullous disease quality of life questionnaire, a tool to measure the quality of life impacts of treatments used in patients with autoimmune blistering disease. Br J Dermatol. 2013;169(5):1000–6. Scholar
  46. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–83.PubMedCrossRefGoogle Scholar
  47. Wijayanti A, Zhao CY, Boettiger D, Chiang YZ, Ishii N, Hashimoto T, Murrell DF. The reliability, validity and responsiveness of two disease scores (BPDAI and ABSIS) for bullous pemphigoid: which one to use? Acta Derm Venereol. 2017;97(1):24–31. Scholar
  48. Xu H-H, Werth VP, Parisi E, Sollecito TP. Mucous Membrane Pemphigoid. Dent Clin N Am. 2013;57(4):611–30. Scholar
  49. Yang B, Chen G, Yang Q, Yan X, Zhang Z, Murrell DF, Zhang F. Reliability and validity of the Chinese version of the autoimmune bullous disease quality of life (ABQOL) questionnaire. Health Qual Life Outcomes. 2017;15(1):31. Scholar
  50. Zhao CY, Murrell DF. Outcome measures for autoimmune blistering diseases. J Dermatol. 2015;42(1):31–6. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.The University of New South WalesSydneyAustralia
  2. 2.Department of DermatologySt. George HospitalSydneyAustralia

Personalised recommendations