Evaluation of a Newly Available ELISA for Envoplakin Autoantibodies for the Diagnosis of Paraneoplastic Pemphigus.

IMPORTANCE: Paraneoplastic pemphigus (PNP) is routinely diagnosed by the presence of autoantibodies for desmoplakin by indirect immunofluorescence (IIF) on rat bladder epithelium (RBE). IIF on RBE has recently been found to be positive in select cases of other blistering disorders. A new ELISA that detects envoplakin autoantibodies has recently been developed for the diagnosis of PNP. In this study, we measure the specificity of IIF on RBE and compare it to the new ELISA. OBSERVATIONS: We measured the specificity of IIF on RBE to be 86% which is on the lower end of the previously reported specificity of 83% to 98.9%. The ELISA for envoplakin autoantibodies has a technical sensitivity of 100%, diagnostic sensitivity of 83%, and specificity of 91%. CONCLUSIONS AND RELEVANCE: This ELISA for envoplakin autoantibodies is now commercially available and technically easier to perform then the immunoblot. We recommend that this new ELISA serves as a confirmatory test in cases of a positive IIF on RBE given its higher specificity.

Comparisons of pathologic and normal skin reactive autoantibodies and the interference phenomenon.

Immunofluorescent serum studies of the roles of the two groups of normal complement-fixing autoantibodies in psoriasis are complicated by the interference phenomenon. Both antibodies have the potential to react in vivo at sites of trauma and in psoriasiform lesions. In serum tests, only one or the other reacts, as demonstrated by immunofluorescent serum tests and absorption studies with isolated stratum corneum antigen. In tests of 15 normal sera, only one consistently reacted with the soluble carbohydrate antigens; the rest consistently reacted with the glycoproteins of the keratin intermediate filaments. This appears to be due to an antibody interference reaction that permits only one of two or more antibodies to react on a given tissue section.

Neonatal linear immunoglobulin a bullous dermatosis: a rare presentation.

Linear immunoglobulin A bullous dermatosis (LABD) is an autoimmune blistering disease that most commonly presents in preschool-aged children. There have been few neonatal reports, all of which had life-threatening aerodigestive complications requiring mechanical intervention and systemic therapy. We present a case of LABD in a neonate who had an uncomplicated course and was treated conservatively with only low-potency topical corticosteroids and wound care before resolution of his skin lesions.

A nonfatal case and 2 fatal cases of paraneoplastic pemphigus: can a complement indirect immunofluorescent test help to identify fatal "group A" paraneoplastic pemphigus cases?

We studied 3 recent cases of paraneoplastic pemphigus (PNP) in detail. Two patients died despite concerted management efforts. One patient received no treatment after the appearance of PNP and recovered completely from both PNP and lymphoma. Multiple serum studies of these 3 patients plus 9 other proven PNP cases revealed that 8 of 9 fatal PNP cases (referred to here as "group A") had distinctive cell surface antibodies detected by complement indirect immunofluorescent (CIIF) tests on monkey esophagus sections. By contrast, none of the sera from 3 patients with PNP who experienced long-term survival (referred to here as "group B") and none of 20 pemphigus vulgaris or 10 pemphigus foliaceus control sera revealed similar beaded cell surface CIIF reaction patterns, a difference that is statistically significant (P <.0001). Cell surface CIIF reaction patterns of group A PNP antibodies resemble the pattern of pemphigus antibody reactions in indirect immunofluorescent tests on the same substrate; however, the latter tend to be thinner and more linear, whereas the cell surface CIIF pattern tends to be more beaded, suggesting possible desmosomal reactions. We believe this test is useful in identifying an aggressive group A form of PNP.

Bullous skin disease: an unusual allergic reaction to vancomycin.

Severe reactions due to vancomycin are uncommon. We describe a case of vancomycin-induced linear immunoglobulin A bullous disease and review the literature pertinent to this entity. This is a rare subepidermal blistering disorder, with a heterogenous clinical presentation. It is characterized by IgA deposition in a linear pattern along the basement membrane zone. It seems to be autoantibody-mediated and is not dose-dependent. Spontaneous and complete skin healing follows vancomycin withdrawal; rechallenge reproduces the disease with a more rapid and severe onset. Because vancomycin is almost never suspected to be the cause of such manifestations, awareness of this rare autoimmune reaction is crucial. Early diagnosis through direct immunofluorescence of the perilesional skin would avoid unnecessary laboratory investigations and therapeutic measures and would shorten significantly the pain and suffering of these patients.

Diagnostic features of pemphigus vulgaris in patients with bullous pemphigoid. Molecular analysis of autoantibody profile.

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.