Diagnostic Features of Pemphigus vulgaris in Patients with Bullous Pemphigoid

Abstract

Background: The simultaneous presence of features of pemphigus vulgaris (PV) in patients with bullous pemphigoid (BP) has previously been reported in the literature. Objective: The purpose of this retrospective study is to present 13 patients with an initial diagnosis of BP, who subsequently demonstrated coexistent serological features of both BP and PV. Methods: The following information on each patient was documented, at the time of initial diagnosis: clinical profile on presentation, histology, direct immunofluorescence, indirect immunofluorescence (IIF) using monkey esophagus as substrate, salt-split skin (SSS) and an immunoblot assay. Since all 13 patients failed to respond to conventional systemic therapy, intravenous immunoglobulin (IVIg) was used as an alternative treatment modality. Prior to initiating IVIg therapy, in all 13 patients, serological studies were performed. In addition to IIF using monkey esophagus, an immunoblot assay and SSS, an enzyme-linked immunosorbent assay (ELISA) was performed to detect antibodies to desmogleins. These different assays were done to identify pathological autoantibodies typical of BP and PV. A control group of 25 healthy normal individuals, 37 patients with BP, 17 patients with PV and 12 patients with pemphigus foliaceus were used for comparison of serological studies. Results: At the time of initial presentation, histological and immunopathological studies confirmed the diagnosis of BP in all 13 patients. Prior to the initiation of IVIg therapy, results of IIF using monkey esophagus as substrate demonstrated high levels of anti-intercellular cement substance (anti-ICS) or antikeratinocyte cell surface antibody. Sera of all 13 patients on SSS bound to the epidermal side of the split. In an immunoblot, using bovine gingival lysate as substrate, sera of 6 patients bound to both a 230-kD (BP Ag1) and 180-kD protein (BP Ag2), while 7 sera bound to only a 230-kD protein. All 13 patients had high levels of antibodies to desmoglein 3 on ELISA. In a pilot experiment, the anti-ICS antibody in sera from 6 random patients was found to be predominantly of the IgG4 subclass. Use of IVIg resulted in an effective clinical response and the maintenance of a prolonged clinical remission. Conclusion: In patients with BP, who are nonresponsive to conventional therapy, the presence of two autoimmune diseases or a dual diagnosis should be considered.

A comparison of anti‐desmoglein antibodies and indirect immunofluorescence in the serodiagnosis of pemphigus vulgaris

“…Subsequent studies in larger groups of patients, however, have shown that PF patients occasionally have Abs to Dsg3 as well, 1,7 and that not all PV and PF patients have Abs to Dsg1 and/or Dsg3 3,5,8 . Furthermore, anti‐Dsg Abs have been occasionally demonstrated in normal controls, and in patients with other bullous diseases, including bullous pemphigoid 1,5,9 . Some investigators have found that a significant minority of patients do not have the PV phenotype predicted by their Dsg autoantibody profile 8 …”

“…3,5,8 Furthermore, anti-Dsg Abs have been occasionally demonstrated in normal controls, and in patients with other bullous diseases, including bullous pemphigoid. 1,5,9 Some investigators have found that a significant minority of patients do not have the PV phenotype predicted by their Dsg autoantibody profile. 8 Despite the commercial availability of ELISAs to detect anti-Dsg1 and anti-Dsg3 Abs, most laboratories still rely on IIF techniques to detect pemphigus autoantibodies.…”

Combined bullous pemphigoid and pemphigus vulgaris in an 18‐year‐old female

“…Only 1 patient had BP appearing 15 years after the onset of PV, however, the patient had anti‐ICS antibodies before, during and after the onset of BP. In the 17 patients with concomitant BP and PV, 70% had cutaneous confined disease, implying a lack of mucosal disease 14 . Ninomiya et al described a patient with BP and PV that was confirmed by DIF and IIF, and on immunoblot was found to be reactive to a 190‐kD protein, possibly implying PNP.…”

Off-label uses of biologics in dermatology: Interferon and intravenous immunoglobulin (Part 1 of 2)

“…IVIG lowers antibody titers to dsg 1 and dsg 3, often making them undetectable. [235][236][237][238][239][240] IVIG has been shown to be effective in the treatment of PV in numerous studies as summarized in Table XVI. In the two largest studies, which are from one institution, 42 patients were treated with IVIG (2 g/kg every 4 weeks) until control was achieved, as defined by healing of old lesions and no new lesions.…”