Histopathology in Relation to Direct Immunofluorescence in Diagnosing IgG-Mediated Pemphigus Diseases: An Ambispective Analysis of Clinical-Laboratory Data from a Single Central European Referral Center

Background/Objectives: Histological examination with hematoxylin and eosin staining (H&E) is commonly used in dermatology, although for autoimmune blistering diseases (AIBD) direct immunofluorescence (DIF) is considered “the gold standard” due to its ability to detect tissue autoimmunity. This study aimed to reassess the value of H&E in the imaging diagnosis of IgG-mediated pemphigus diseases. Methods: In a 10-year, single-center, ambispective study, a total of 33 patients with a diagnosis of IgG-mediated pemphigus diseases already made with DIF examination, in whom H&E was also performed, were analyzed. A six-parameter multiplex ELISA or monoanalyte ELISAs were mainly used to distinguish between pemphigus vulgaris (PV) and pemphigus foliaceus (PF). PV was diagnosed in 22 and PF in 11 cases. H&E images were then examined for intraepithelial separation (superficial PF, suprabasal PV) and acantholysis. Skin sections were also examined for intra-adnexal separation. Results: H&E pemphigus features were revealed less frequently compared to DIF results in both PV and PF as well as in the total PV + PF group. In PV, both suprabasal separation and acantholysis were detected in 86.4% of patients. In PF, superficial separation was detected in 45.5% of cases and acantholysis in 72.7%. Of 21 cases with visible adnexal structures, intra-adnexal separation was detected in 47.6% patients (PV 57.1%, PF 28.6%). Intraepithelial separation was statistically significantly more often found in the PV group than in the PF group. When selecting patients for this study, the DIF and ELISA results were equivocal in three cases, but H&E helped rule out pemphigus-type pathology. Conclusions: All studied H&E features were less frequently detected than a typical DIF image. Potentially, when clinical picture, DIF, and serology are concordant, H&E has more of a complementary role; however this hypothesis must be verified in larger multicenter studies. Nevertheless, H&E is an essential tool in excluding alternative diagnoses.