Mucosal Involvement in Bullous Pemphigoid Is Mostly Associated with Disease Severity and to Absence of Anti-BP230 Autoantibody

Abstract

Bullous pemphigoid (BP) is the most common autoimmune bullous disease and typically affects the elderly. Binding of specific autoantibodies to BP180/230 hemidesmosomal components induces an inflammatory response leading to skin blister formation. Unusual manifestations of BP include additional mucous membrane involvement, without pathophysiological knowledge associated to the formation of these lesions. We here performed a prospective study on series of consecutive BP patients with (n = 77) and without (n = 18) mucosal involvements at baseline to further investigate why some BP patients display mucosal lesion and other not. Analysis of disease activity showed that BP patients with mucosal involvement displayed a higher total BP Disease Area Index (BPDAI) score (P = 0.008), but also higher skin and blister/erosion BPDAI scores (P = 0.02 and P = 0.001, respectively). By contrast, the erythema/urticaria BPDAI score was identical between the two groups of patients. The erythema/urticaria BPDAI score, but not the blister/erosion BPDAI score, was correlated with the serum concentration of anti-BP180 NC16A autoantibodies in patients with mucosal involvement. In multivariate analysis, the absence of anti-BP230 autoantibody was the only factor independently associated with mucosal involvement (OR 7.8; 95% CI, 3.1-19.6) (P < 0.0001). Analysis of the distribution of BP patients according to BPDAI scores revealed a shift toward higher blister/erosion BPDAI scores for BP patients with mucosal involvement. This study indicates that mucosal lesions are clinically mainly related to disease severity and immunologically to the absence of anti-BP230 antibodies.

Keywords: BP Disease Area Index; anti-BP230; autoantibodies; bullous pemphigoid; mucosal involvement.

Figure 1

Distribution of the whole bullous pemphigoid (BP) patients (n = 95) (A) and of BP patients without (n = 77) (B) and with (n = 18) (C) mucosal involvement according to total BP Disease Area Index (BPDAI) values at the time of diagnosis. In the whole BP group and in the subgroup of BP without mucosal involvement, the number of BP included decrease when the values of the BPDAI increased, whereas BP patients with mucosal involvement were evenly distributed. Comparison of the cumulative distribution by the Kolmogorov–Smirnov test showed significant difference between BP patients with (C) and without (B) mucosal involvement (D = 0.6154; P = 0.008).

Figure 2

Distribution of both bullous pemphigoid (BP) patients with (white column) and without (gray column) mucosal involvement according to erythema/urticaria BP Disease Area Index (BPDAI) values (A) and blisters/erosions BPDAI values (B) at the time of diagnosis. No statistical differences were observed between the distributions of these two BP groups according to the Kolmogorov–Smirnov test, although a clear different distribution could be visualized within the low (0–19) and within the high (50–79) values of the blisters/erosions BPDAI values (B).

Figure 3

Correlation of serum anti-BP180 NC16A titers with total BP Disease Area Index (BPDAI) (A,E), total skin BPDAI (B,F), blister/erosion BPDAI (C,G), and erythema/urticaria BPDAI (D,H) scores in bullous pemphigoid patients without (A–D) or with (E–H) mucosal involvement. The correlation coefficients and statistical significances were calculated according to Spearman’s correlation test and are summarized in Table 4.