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

Discussion

The main objective of this study was to propose cut-off values based on the ABSIS and PDAI scoring systems, allowing classification of patients into three subgroups according to the extent of pemphigus (moderate, significant and extensive disease). It must be underlined that these scores assess disease extent, which is not identical to disease severity, as the prognostic relevance of these scores and their consequences in term of treatment options have not yet been evaluated.

Our results suggest that a PDAI activity value of 15 points and an ABSIS value of 17 points allow differentiation between moderate and significant pemphigus forms, whereas a PDAI activity value of 45 points and an ABSIS value of 53 points allow differentiation between significant and extensive pemphigus forms.

The three subgroups defined by these cut-off values differed from each other not only by their respective median ABSIS (P < 0·001) and PDAI scores (P < 0·001), but also by their median PGA (P < 0·001) and DLQI scores (P < 0·005 or P < 0·017). Moreover, using ABSIS cut-off values allowed excellent separation from the PDAI score and vice versa.

The extensive pemphigus subgroup defined by the 45- and 53-point cut-off values based on the PDAI and ABSIS scores, respectively, had a high median PGA score (8 out of 10 points) and high median DLQI score (12 or 14 out of 30 points). These figures closely reflected both the investigator's and the patient's evaluation of disease extent. In contrast, the moderate subgroup defined by the 15- and 17-point cut-off values had rather low median PGA and DLQI scores of 4 and 6, respectively, which again correlated well with the evaluation of both investigators and patients. Therefore, despite the fact that the 25th and 75th percentiles used to calculate the cut-off values were somewhat arbitrary, although often used, the three disease activity subgroups defined this way correlated well and fitted with the quick overall assessment of the patient made by the investigator. In fact, the median PGA scores were 4, 6 and 8 out of 10 points, corresponding to the moderate, significant and extensive subgroups defined by the percentile method.

As expected, most patients with PV with both cutaneous and mucosal involvement were classified in the significant to extensive subgroups, whereas most patients with PV with exclusive mucosal involvement were found in the moderate to significant subgroups, which strengthens the validity of the proposed cut-off values. Interestingly, these cut-off values also allowed classification of three and six patients with PV with exclusive but extensive mucosal involvement into the extensive subgroup (according to the PDAI and ABSIS cut-off values, respectively). Similarly, whereas most patients with PF were classified in the moderate to significant subgroups, five (PDAI) and four (ABSIS) patients with PF with a mean 50% body surface area involvement were classified in the extensive subgroup.

However, one could ask whether the proposed cut-offs are valid for all clinical subtypes of pemphigus (exclusive cutaneous involvement, exclusive mucosal involvement and involvement of both). Although this complementary analysis of cut-off values in each clinical subgroup was performed in a limited number of patients, we observed that the PDAI cut-off values were slightly lower in the subgroups of patients with exclusive mucosal or exclusive skin involvement than in the subgroup of patients with both skin and mucosal involvement. Conversely, the ABSIS cut-off values were much higher in patients with exclusive mucosal or mucocutaneous involvement than in those with exclusive cutaneous involvement. This is most likely due to the presence of a subjective component in the ABSIS mucosal assessment but not in the PDAI scoring system. As the PDAI cut-off values were close for the whole pemphigus population (both PF and PV), they could be used for all forms of pemphigus. However, as there were higher thresholds for mucosal involvement with ABSIS, it might be useful to have different cut-off scores for cutaneous and mucosal involvement.

The 15- and 45-point cut-off values proposed for the PDAI severity score in the present study are somewhat higher than the 9 and 25 points proposed by Shimizu et al. in a Japanese study that enrolled 37 patients with pemphigus.[12] These differences might be due to the fact that their study included both newly diagnosed and previously treated patients, with few severe cases. Indeed, two-thirds of the evaluations in the Japanese study were performed in already treated and/or relapsing patients, with only 11 of the 110 assessments considered severe according to the physician's subjective impression. Therefore, it is likely that this particular recruitment may have been responsible for the inclusion of a higher number of patients with limited disease than in our series, which recruited only newly diagnosed untreated incident cases. Additionally, we cannot exclude that some features of patients with pemphigus in Japan may differ from those in our multicentre international study.

A selection bias is unlikely in our prospective multicentre study, as it included a large number of consecutive newly diagnosed patients recruited in both secondary and tertiary care centres. One may hypothesize that some patients could have been treated by a general practitioner and never needed to be referred to a dermatology department, thus leading to underestimation of the proportion of the limited and moderate types of pemphigus. However, this is unlikely, as in Europe, where most patients in this study are from, all patients with pemphigus are referred to the inpatient or outpatient clinic of dermatology departments, especially for diagnosis and to discuss treatment options. In fact, the present study included patients with a wide range of severities, whereas previous studies included only a limited number of patients, most of them already treated and with limited lesions.[9] Despite the recruitment of consecutive incident cases of pemphigus, we observed that the severity scores of the whole group of patients were distributed over the lowest third of the PDAI and ABSIS scales. A prospective longitudinal study is currently being conducted to determine whether this usage of a limited portion of the ABSIS and PDAI scales impairs the sensitivity of these scores in detecting improvement or worsening of the patient's condition.

We did not assess here the reproducibility of these scores between investigators. However, good correlation between the ABSIS and PDAI scoring systems, as well as between these scores and PGA and DLQI scores, suggests acceptable reproducibility of these scoring systems. Moreover, the observation that the Spearman correlation coefficients calculated in the present study (r = 0·69 for PDAI/PGA and r = 0·56 for ABSIS/PGA) were close to those reported by Rosenbach et al. (r = 0·60 for PDAI/PGA and r = 0·43 for ABSIS/PGA)[9] and by Rahbar et al. (r = 0·67 for PDAI/PGA and r = 0·33 for ABSIS/PGA)[13] also suggests the acceptable reproducibility of these scores.

In conclusion, identifying three subgroups of moderate, significant and extensive pemphigus should help physicians to classify and manage affected patients. Furthermore, this should facilitate reporting of outcomes, and enable direct comparisons between treatment regimens in future prospective trials.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....