Brunsting-Perry pemphigoid: A retrospective case series of a frequently unrecognized condition
Authors: Valentina Imstepf, Simone Cazzaniga, Helmut Beltraminelli, Luca Borradori, Laurence Feldmeyer
Journal: Journal of the American Academy of Dermatology (2020)

Brunsting-Perry pemphigoid (BPP) constitutes a rare variant of mucous membrane pemphigoid (MMP). Since the first description of 7 cases, there have been only a few case reports describing the characteristics of BPP.1Brunsting L.A. Perry H.O. Benign pemphigoid? A report of seven cases with chronic, scarring, herpetiform plaques about the head and neck.AMA Arch Dermatol. 1957; 75: 489-501Crossref PubMed Scopus (121) Google Scholar,2Bernard P. Borradori L. Pemphigoid group.in: Bolognia J.L. Schaffer J.V. Cerroni L. Dermatology. Elsevier, 2018: 510-526Google Scholar We retrospectively assessed all patients with BPP evaluated in our tertiary referral center between 2016 and 2019. The data were retrieved from our databank. Diagnosis of BPP was based on 1) clinical features; 2) histopathologic findings; and 3) positive direct immunofluorescence microscopy studies with linear deposits of IgG, IgA, and/or C3 along the dermoepidermal junction.3Murrell D.F. Marinovic B. Caux F. et al.Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts.J Am Acad Dermatol. 2015; 72: 168-174Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar We identified 12 patients complying with the inclusion criteria. Patient characteristics and findings are depicted in Table I. The mean age at presentation was 73 years, and 80% of the patients were male; 36.4% had diabetes mellitus type II, 72.7% had arterial hypertension, 54.5% had chronic renal insufficiency, and 1 patient had colon cancer. There were 3 DPP-4 inhibitor-treated patients (25%), and 4 patients (33.3%) received sartans. Ten of 11 patients (data missing for 1 patient) were treated with topical steroids. Among them, 8 had a relapse and required an additional treatment with methotrexate and/or tetracyclines. Complete remission, partial remission on minimal therapy, and persistent disease were observed in 33.3%, 50%, and 16.7%, respectively.Table IDemographics, clinical characteristics, and histologic parameters of the patients includedPatient characteristicsn (N = 12)%MeanSDSex Female216.7 Male1083.3Age at diagnosis, y73.111.2Age at symptom onset, y70.912.4Diagnostic delay, y3.04.7Localization∗More than 1 category may be present at the same time.12 Head/face/neck12100.0 Upper body541.7 Oral433.3 Other18.3Clinical features∗More than 1 category may be present at the same time.12 Bullous lesions866.7 Ulcerations1191.7 Erosions866.7 Scales325.0Histologic diagnosis∗More than 1 category may be present at the same time.12 Spongiosis18.3 Scarring/fibrosis541.7 Subepidermal blister758.3 Eosinophils866.7 Erosions541.7 Other325.0DIF∗More than 1 category may be present at the same time.12 Linear C3/IgG1191.7 Other linear autoantibodies541.7 Unspecific DIF18.3ELISA11 BP180327.3 BP23019.1 BP180 + 23019.1 Negative654.5 No data1—IIF10 Positive†All IIF-positive patients (n = 4) were evaluated in the roof of the bulla.440.0 Negative660.0 No data2—ELISA + IIF∗More than 1 category may be present at the same time.10 Both negative440.0 At least 1 positive660.0 Both positive220.0 No data2—DIF, Direct immunofluorescence; ELISA, enzyme-linked immunosorbent assay; IIF, indirect immunofluorescence; SD, standard deviation.∗ More than 1 category may be present at the same time.† All IIF-positive patients (n = 4) were evaluated in the roof of the bulla. Open table in a new tab DIF, Direct immunofluorescence; ELISA, enzyme-linked immunosorbent assay; IIF, indirect immunofluorescence; SD, standard deviation. This review of 12 cases represents the largest series of BPP reported so far in the English literature. Without any exceptions, the lesions involved the head, face, or neck, and in more than 40%, also the upper body. More than 90% of our patients presented with erosions, ulcerations, and prurigo-like lesions, and obvious blistering was absent in almost half the patients (Fig 1). In one third of the cases, mild oral mucosal involvement occurred, which has been only anecdotally reported in BPP.1Brunsting L.A. Perry H.O. Benign pemphigoid? A report of seven cases with chronic, scarring, herpetiform plaques about the head and neck.AMA Arch Dermatol. 1957; 75: 489-501Crossref PubMed Scopus (121) Google Scholar,2Bernard P. Borradori L. Pemphigoid group.in: Bolognia J.L. Schaffer J.V. Cerroni L. Dermatology. Elsevier, 2018: 510-526Google Scholar The polymorphic presentation likely explains the long mean diagnostic delay of 3 years observed in our series. Immunologically, the majority of our patients with BPP showed reactivity for BP180 and/or BP230, although the available data indicate that the targeted autoantigens of BPP are heterogenous, including type VII collagen and laminin 332.2Bernard P. Borradori L. Pemphigoid group.in: Bolognia J.L. Schaffer J.V. Cerroni L. Dermatology. Elsevier, 2018: 510-526Google Scholar There is no validated therapeutic approach for BPP. Based on our observations, potent topical steroids should be the first-line therapeutic option. If this does not control the disease, either low-dose methotrexate and/or tetracyclines appear to be good second-line options.3Murrell D.F. Marinovic B. Caux F. et al.Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts.J Am Acad Dermatol. 2015; 72: 168-174Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar These regimens resulted in either complete or partial control of the disease with minimal treatment in more than 80% of our cases. In our study, 7 patients with BPP were either taking DPP4is or sartans. Drug-induced MMP has been only anecdotally described.2Bernard P. Borradori L. Pemphigoid group.in: Bolognia J.L. Schaffer J.V. Cerroni L. Dermatology. Elsevier, 2018: 510-526Google Scholar,4Gaudin O. Seta V. Alexandre M. et al.Gliptin accountability in mucous membrane pemphigoid induction in 24 out of 313 patients.Front Immunol. 2018; 9: 1030Crossref PubMed Scopus (25) Google Scholar DPP4is, as well as anti-PD1 inhibitors, have been associated with MMP and BP.4Gaudin O. Seta V. Alexandre M. et al.Gliptin accountability in mucous membrane pemphigoid induction in 24 out of 313 patients.Front Immunol. 2018; 9: 1030Crossref PubMed Scopus (25) Google Scholar Hence, our findings suggest that DPP4is may be a potential trigger of BPP. Furthermore, sartans have been incriminated in triggering both BP and MMP.4Gaudin O. Seta V. Alexandre M. et al.Gliptin accountability in mucous membrane pemphigoid induction in 24 out of 313 patients.Front Immunol. 2018; 9: 1030Crossref PubMed Scopus (25) Google Scholar,5Saraceno R. Citarella L. Spallone G. Chimenti S. A biological approach in a patient with psoriasis and bullous pemphigoid associated with losartan therapy.Clin Exp Dermatol. 2008; 33: 154-155Crossref PubMed Scopus (40) Google Scholar In summary, dermatologists should consider BPP in the presence of chronic localized erosions, ulcerations, blisters, and prurigo-like lesions with scarring affecting the head and upper portion of the trunk in an elderly patient. Histologically, eosinophilia with erosion or subepidermal blistering is observed in the majority of the BPP cases. Nevertheless, the definite diagnosis depends on the results of the direct immunofluorescence microscopy findings.