Management of Cutaneous Lesions in Brunsting–Perry Pemphigoid (Bpp): A Single-Center Retrospective Cohort Study

Brunsting–Perry pemphigoid (BPP) is a rare, autoimmune skin disorder within the spectrum of mucous membrane (cicatricial) pemphigoid characterized by subepidermal blistering of the head, neck, and shoulders [1, 2]. The development of autoantibodies against hemidesmosomal proteins including BP180 and BP230 disrupts the integrity of the epidermal basement membrane [2-4]. BPP's rarity has precluded extensive study [4, 5]. We assessed the outcomes of 10 BPP patients treated with methotrexate (MTX) or mycophenolate mofetil (MMF).

Institutional review board was obtained to review the medical records of patients evaluated at Wake Forest Baptist Health's dermatology clinic who received MTX or MMF for BPP skin lesions between 2010 and 2020. Diagnoses were established based on (1) clinical features of lesions, (2) positive direct immunofluorescence (DIF) assays ($\pm$C3 deposits along the basement membrane zone), (3) histopathologic findings, and (4) ELISA/immunoblot positivity. Patients who did not meet these criteria were excluded. Outcomes were categorized as complete response (CR) (asymptomatic, no new lesion development), partial response (PR) (improving lesions, reduced erythema and inflammation), and no response (NR).

Our patients were primarily White (100%) males (60%) with a mean age of 62 years (range: 48–82) (Table 1). Lesions were presented on the trunk (40%), face (20%), mouth (70%), scalp (40%), and genitals (10%) (Figure 1). Patients had face (25%), scalp (50%), and buccal mucosal biopsies (25%) (Figure 2). Seven patients (70%) had positive ELISA results for IgG antibodies against full-length BP 180 recombinant proteins; four patients (40%) had positive anti-BP 230 IgG antibodies. All patients (100%) had negative antibody production against collagen VII. Patients had a mean disease duration of 27 and 42 months before MTX and MMF initiation, respectively. Medications failed before MTX or MMF included topical corticosteroids (30%), prednisone (30%), tacrolimus “swish and spit” (20%), magic mouthwash (hydrocortisone, lidocaine, diphenhydramine, nystatin) (30%), doxycycline (20%), minocycline (10%), dapsone (10%), and azathioprine (10%). Seven patients (70%) were systemic therapy naïve. Three patients (30%) had pretreatment systemic therapy failure on a mean prednisone dose of 21.7 mg.

Two treatment groups were analyzed: MTX and MMF. Patients received either MTX or MMF as initial treatment. Six patients received treatment with MTX; four with MMF (Table 2). One patient was discontinued from MTX and started on MMF. Mean time to initial response was 2.9 months (standard deviation [SD], 1.9 months) and 2.7 months (SD, 2.4 months) for MTX and MMF, respectively (Table 2). Five patients (83.3%) treated with MTX achieved CR within a mean of 16.1 months; mean time to PR on MTX was 13.2 months (SD, 11.8 months). One patient (16.7%) had NR and was later switched to MMF. Four patients (100%) treated with MMF achieved CR within a mean of 17.5 months; mean time to PR on MMF was 15.7 months (SD, 11.9 months). Seven patients (70%) relapsed with flares over a mean follow-up period of 20.1 (SD 12.2 months) (time from initial response to most recent follow-up visit). MTX and MMF were well tolerated by most patients (90%) with minimal side effects being primarily gastrointestinal manifestations; none of the patients discontinued therapy.

BPP often requires systemic treatment. Although this study was limited by its small sample size, retrospective design, and lack of standardized outcome measures, cutaneous lesions improved in most patients (90%) after initiating treatment with MMF or MTX. A stepwise treatment approach starting with MTX and MMF may be a suitable option for managing BPP. While treatment data for BPP remains sparse, it appears MTX and MMF may be options to consider for moderate-to-severe, actively inflamed BPP.

(i) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data- Shirley Parraga, Matthew Hrin, Sarah Rimmer, Joseph Jorizzo; (ii) drafting the article or revising it critically for important intellectual content- Shirley Parraga, Matthew Hrin, Sarah Rimmer, Joseph Jorizzo; (iii) final approval of the version to be published- Shirley Parraga, Matthew Hrin, Sarah Rimmer, Joseph Jorizzo; (iv) collection of data- Shirley Parraga, Matthew Hrin; (v) general supervision of the research group- Joseph Jorizzo.

The authors have nothing to report.

All patients in this manuscript have given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Reviewed and approved by Wake Forest University Health Sciences IRB #00075066.

Consent for the publication of recognizable patient photographs or other identifiable material was obtained by the authors and included at the time of article submission to the journal stating that all patients gave consent with the understanding that this information may be publicly available.

The authors declare no conflicts of interest.

Shirley Parraga