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

C. Boulard; S. Duvert Lehembre; C. Picard-Dahan; J.S. Kern; G. Zambruno; C. Feliciani; B. Marinovic; P. Vabres; L. Borradori; C. Prost-Squarcioni; B. Labeille; M.A. Richard; S. Ingen-Housz-Oro; E. Houivet; V.P. Werth; D.F. Murrell; M. Hertl; J. Benichou; P. Joly

Disclosures

The British Journal of Dermatology. 2016;175(1):142-149. 

In This Article

Materials and Methods

Study Population

We conducted a prospective multicentre study in 31 French, German, Italian, Swiss, Croatian and Australian Departments of Dermatology (secondary and tertiary care centres). This study was approved by the corresponding local ethics committees.

Consecutive patients aged ≥ 18 years with pemphigus newly diagnosed between July 2009 and May 2012 were included. All included patients had given signed informed consent. Diagnosis of either PV or PF was based on (i) characteristic clinical features; (ii) histological analysis of a skin or mucosal biopsy showing acantholysis, intraepithelial blistering or eosinophilic spongiosis; (iii) direct immunofluorescence examination showing IgG and/or C3 deposits on the keratinocyte cell membrane; and (iv) detection of circulating autoantibodies by commercially available enzyme-linked immunosorbent assays for desmoglein 3 and desmoglein 1 (MBL, Nagoya, Japan).

Assessment of Disease Extent

Disease extent was evaluated using ABSIS,[8] PDAI[9] and PGA scores. The ABSIS score of cutaneous involvement is based on the extent of the body surface area, assessed using Wallace's 'rule of nines' and the type of skin lesions.[8] The percentage of the body surface area affected is multiplied by an index reflecting the predominant lesions: 1·5 (erosive, exudative lesions, bullae or Nikolsky sign positivity), 1·0 (erosive, dry lesions) or 0·5 (re-epithelialized lesions). ABSIS oral involvement is evaluated by scoring 11 mucosal sites as 1 (presence of lesions) or 0 (absence of lesions), and by completing a subjective severity scale based on discomfort during eating and drinking. Using higher scores to denote worse disease, ABSIS ranges from 0 to 206 points, with 150 points for skin involvement, 11 points for oral involvement and 45 points for subjective discomfort.

The PDAI has a score ranging from 0 to 263 points, with 250 points representing disease activity (120, 10 and 120 points for skin, scalp and mucosal activity, respectively) and 13 points representing disease damage.[9] However, the damage component was not included in the present analysis. For skin activity assessment, 12 anatomical sites are assigned a score according to disease extent: 0 (no lesions); 1 (one to three lesions, up to one lesion > 2 cm in any diameter, all ≤ 6 cm); 2 (two or three lesions, at least two lesions > 2 cm, all ≤ 6 cm); 3 (more than three lesions, all ≤ 6 cm); 5 (more than three lesions and/or one lesion > 6 cm); or 10 (more than three lesions and/or at least one lesion > 6 cm or the entire area affected). Scalp activity is assigned a score based on the presence of blisters, erosions or erythema of: 0 (no activity); 1 (one quadrant affected); 2 (two quadrants affected); 3 (three quadrants affected); 4 (whole skull affected); or 10 (at least one lesion > 6 cm). For mucosal activity assessment, 12 mucosal sites are assigned a score based on the presence of erosions or blisters: 0 (absent); 1 (one lesion); 2 (two or three lesions); 5 (more than three lesions or two lesions > 2 cm); or 10 (entire area).

PGA is a 10-point visual analogue scale, based on a physician's subjective impression from 0 (no lesions) to 10 (worst skin and mucosal condition imaginable). It has been used in clinical trials because it is fast and easy to use.[10]

Patients' quality of life was evaluated by the Dermatology Life Quality Index (DLQI) translated into different languages.[11] It includes 10 questions and has a total score between 0 and 30.

Statistical Analysis

The baseline ABSIS, PDAI, PGA and DLQI scores were prospectively recorded on case report forms. Observations with more than one missing score out of four were excluded from the analysis. The target sample size (n = 100) was calculated for the primary objective of this study, which was to assess reproducibility and inter-rater agreement.

Quantitative variables were reported as median (range), and qualitative variables as frequency (%). Correlations between the different scoring systems (ABSIS, PDAI activity, PGA and DLQI) were assessed using Spearman's rank correlation coefficient. Separately for the ABSIS and PDAI scoring systems, three subgroups of severity – moderate, significant and extensive – were arbitrarily defined based on the 25th and 75th score percentiles. Moderate, significant and extensive pemphigus corresponded to cases with a score lower than the 25th percentile of the sample, higher than or equal to the 25th and lower than the 75th percentile, and higher than or equal to the 75th percentile, respectively. From these defined categories, the median scores of the three severity subgroups (moderate, significant and extensive) were compared between these three subgroups, separately for each score (i.e. median PDAI activity scores were compared between the three severity subgroups from the PDAI and similarly for the ABSIS). In order to validate the classification in the three severity subgroups, we first compared the median PDAI scores of the three subgroups defined by the ABSIS cut-off values and vice versa. Then we compared the median PGA and DLQI scores of the three subgroups of disease extent defined by the cut-off values calculated from the PDAI and the ABSIS scoring systems. All of these comparisons relied on the nonparametric Kruskal–Wallis test. Statistical analyses were performed using GraphPad Prism Version 5.0 (GraphPad Software, La Jolla, CA, U.S.A.).

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