Pemphigus Disease Activity Measurements: Pemphigus Disease Area Index, Autoimmune Bullous Skin Disorder Intensity Score, and Pemphigus Vulgaris Activity Score
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.
KeywordsPemphigus Autoimmune Blistering Bullous Disease activity Disease damage Measure Score Severity PDAI
- 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. https://doi.org/10.1111/bjd.14405.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1111/j.1468-3083.2012.04717.x.CrossRefPubMedGoogle Scholar
- 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
- 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. https://doi.org/10.1016/S0140-6736(17)30070-3.CrossRefGoogle Scholar
- 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. https://doi.org/10.1111/j.1365-2133.2012.10929.x.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1016/j.jdermsci.2013.02.011.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1007/s11136-010-9606-8.CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1016/j.jaad.2008.01.012.CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.2340/00015555-1666.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1001/jamadermatol.2013.8175.CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1038/jid.2009.72.CrossRefPubMedPubMedCentralGoogle Scholar
- 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. https://doi.org/10.1111/1346-8138.12649.CrossRefPubMedGoogle Scholar