Prevalence and clinical markers of herpes simplex virus infection in oral lesions of bullous pemphigoid

Abstract

Background: The manifestations of bullous pemphigoid (BP) and herpes simplex virus (HSV) infection are similar in oral mucosa, and the laboratory detection of HSV has some limitations, making it difficult to identify the HSV infection in oral lesions of BP. In addition, the treatments for BP and HSV infection have contradictory aspects. Thus, it is important to identify the HSV infection in BP patients in time.

Objective: To identify the prevalence and clinical markers of HSV infection in oral lesions of BP.

Methods: This prospective cross-sectional descriptive analytical study was conducted on 42 BP patients with oral lesions. A total of 32 BP patients without oral lesions and 41 healthy individuals were enrolled as control groups. Polymerase chain reaction was used to detect HSV. Clinical and laboratory characteristics of patients with HSV infection were compared with those without infection.

Results: A total of 19 (45.2%) BP patients with oral lesions, none (0.0%) BP patients without oral lesions, and four (9.8%) healthy individuals were positive for HSV on oral mucosa. Among BP patients with oral lesions, the inconsistent activity between oral and skin lesions (p=0.001), absence of blister/blood blister in oral lesions (p=0.020), and pain for oral lesions (p=0.014) were more often seen in HSV-positive than HSV-negative BP patients; the dosage of glucocorticoid (p=0.023) and the accumulated glucocorticoid dosage in the last 2 weeks (2-week AGC dosage) (p=0.018) were higher in HSV-positive BP patients. Combining the above five variables as test variable, the AUC was 0.898 (p<0.001) with HSV infection as state variable in ROC analysis. The absence of blister/blood blister in oral lesions (p=0.030) and pain for oral lesions (p=0.038) were found to be independent predictors of HSV infection in multivariable analysis. A total of 14 (73.7%) HSV-positive BP patients were treated with 2-week famciclovir and the oral mucosa BPDAI scores significantly decreased (p<0.001).

Conclusion: HSV infection is common in BP oral lesions. The inconsistent activity between oral and skin lesions, absence of blister in oral lesions, pain for oral lesions, higher currently used glucocorticoid dosage, and higher 2-week AGC dosage in BP patients should alert physicians to HSV infection in oral lesions and treat them with 2-week famciclovir in time.

Keywords: Bullous pemphigoid; HSV; autoimmune subepidermal bullous disease; clinical markers; infection; oral lesions; prevalence.

Figure 1

Results of agarose gel electrophoresis of PCR products. (A) Agarose gel electrophoresis of PCR products for HSV-1 DNA (142 bp). M, molecular weight marker (DNA ladder, 100 bp); lane 1–4,7, positive for HSV-1; lane 5,6, negative for HSV-1; lane 8, positive control for HSV-1; lane 9, negative control for HSV-1. (B) Agarose gel electrophoresis of PCR products for HSV-2 DNA (391 bp). M, molecular weight marker (DNA ladder, 100 bp); lanes 1–3, positive for HSV-2; lane 4–7, negative for HSV-2; lane 8, positive control for HSV-2; lane 9, negative control for HSV-2. (C) Agarose gel electrophoresis of PCR products for β2-microglobulin DNA (102 bp). M, molecular weight marker (DNA ladder, 100 bp); all samples were detected positive for β2-microglobulin DNA.

Figure 2

ROC curves of the variables with significant differences between HSV-positive and HSV-negative subgroups. (A–E) The inconsistent activity between oral and skin lesions (A), absence of blister/blood blister in oral lesions (B), pain for oral lesions (C), dosage of glucocorticoid (D), and 2-week AGC dosage (E) can significantly distinguish HSV-positive subgroup from HSV-negative subgroup (all p<0.05). (F) All the above variables were combined as the test variable, and the combined variable can get the highest diagnosis probability (AUC=0.898, p<0.001). (G) All the ROC curves were organized together to directly show that the combined variable has the biggest AUC. AUC, area under the curve; 2-week AGC dosage, accumulated glucocorticoid dosage in the last 2 weeks.

Figure 3

Oral lesions of BP with HSV infected before (A) and after (B) famciclovir therapy. (A) Several erythema and erosions covered with yellowish-white pseudomembranes distributed on the left buccal mucosa and were positive for HSV-1 by PCR. (B) The oral lesions almost completely healed after a 2-week treatment of famciclovir.