Klementyna KęPińska

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.

Background: Pemphigus diseases are rare autoimmune blistering disorders mediated by pathogenic autoantibodies directed mainly against desmoglein 1 and desmoglein 3. Although most cases are considered idiopathic, external triggers that can disrupt immune tolerance have been described. Vaccination has been discussed as a potential precipitating factor in autoimmune skin diseases. However, the relationship between vaccination and the induction of pemphigus-related autoantibodies has not been comprehensively summarized. Methods: We conducted a narrative review of all available studies published in the last 25 years identified through medical databases, excluding studies on COVID-19 vaccinations. Reports describing either new-onset pemphigus or exacerbation of preexisting pemphigus with a temporal association to vaccination were included. Clinical characteristics, vaccine type, latency period, direct immunofluorescence findings, and ELISA results for desmoglein autoantibodies were analyzed. In addition, we present our own clinical-laboratory experience illustrating this issue. Results: The current evidence consists predominantly of case reports and small case series. Published cases describe pemphigus vulgaris and pemphigus foliaceus occurring after vaccinations against influenza, hepatitis B, tetanus, diphtheria, pertussis, rabies, and other routinely administered immunizations. The latency period most often ranged from several days to a few weeks. Immunopathological findings were consistent with classical pemphigus diseases, including intercellular IgG deposits in the epidermis and circulating autoantibodies against desmoglein 1 and/or desmoglein 3. Our patient was a 78-year-old woman who developed cutaneous form of pemphigus vulgaris, diagnosed with direct immunofluorescence (DIF) and multiplex ELISA, 10 days after diphtheria–tetanus–pertussis vaccination. The patient had a positive family history of autoimmune blistering disease, namely mucous membrane pemphigoid. Conclusions: Based on the currently available evidence, a direct causal relationship between vaccination and pemphigus diseases cannot be established. Nevertheless, accumulated clinical and serological observations suggest that vaccination may act as a triggering factor in genetically or immunologically predisposed individuals, possibly by amplifying pre-existing subclinical autoreactive immune responses. Further population-based and mechanistic studies are required to clarify this association, while the overall benefits of vaccination remain substantial.