Evaluation of the possible association between acantholysis and anti‐desmogleins 1 and 3 values in pemphigus vulgaris and pemphigus foliaceus

Acantholysis is the main pathologic finding in pemphigus, and its location has been historically used to distinguish the major subtypes of pemphigus vulgaris (PV) and pemphigus foliaceus (PF). While suprabasal clefts are present in PV, PF includes intragranular or subcorneal clefts. After the introduction of anti‐desmoglein ELISA, PF is characterized by anti‐Dsg 1 and PV by anti‐Dsg 3 autoantibodies. However, pathological and serological findings are not consistent in all patients. In this study, we tried to investigate the agreement between serological and pathological findings for the diagnosis of pemphigus.


| INTRODUC TI ON
Pemphigus is a group of rare autoimmune bullous diseases, characterized by blisters on skin and/or mucous membranes. It is caused by the autoantibodies against desmosomal glycoprotein expressed on keratinocytes, such as desmoglein (Dsg) 1 and Dsg 3, which result in intra-epidermal acantholysis and bullous formation. 1 Recent studies have shown that Dsg1/3 ELISA and histological findings may be discordant in some cases. 8 The aim of the present study is to investigate the association of the location of acantholysis and the level of anti-Dsg 1 and anti-Dsg 3 index value in PV and PF. We also determined the overall agreement between the histological and serological findings in the diagnosis of PV and PF to obtain a better understanding of the role of different diagnostic methods in pemphigus.

| Data collection
The report of the ELISA index value of anti-Dsg 1 and anti-Dsg 3 was obtained from patients' medical records and subdivided into positive and negative groups with a cut-off level of 20 U/mL. In each case,  The overall agreement of histological and serological methods, regarding differentiating PV and PF cases, was calculated. P-value <.05 was considered statistically significant.

| Patients characteristics
In total, 168 patients, aging from 20 to 84 years old (mean of 49 ± 14.2) consisted of 94 men (56%) and 74 women (44%), were included. There were 123 cases of PV and 35 cases of PF, distinguished based on the status of anti-Dsg 1 and anti-Dsg 3 ELISA. In 10 patients, acantholysis, anti-desmoglein antibody, pemphigus, pemphigus foliaceus, pemphigus vulgaris the serological test was negative for both anti-Dsg 1 and 3. Although their pathological characteristics were consistent with PV in eight and with PF in two, they were assigned in neither PV nor PF groups. Anti-Dsg 1 and 3 values ranged from 0.7 to >200 U/mL (mean: 138.74 U/ mL) and 1 to >200 U/mL (mean: 126.61 U/mL), respectively.

| Histopathological findings
Histopathological findings revealed that the location of acantholysis was on the upper half of the epidermis in 33 (19.6%) cases, the lower half of epidermis in 100 cases (59.5%), and throughout the epidermis in 35 (20.8%) cases.  Table 1).

| The association between anti-Dsg antibodies and histopathological findings
As Table 1    In this study, we investigated the association between the histological features and the antibodies' profile in Iranian population.

| D ISCUSS I ON
As it is well-known, the serological characteristics of pemphigus are strongly related to the genetic factors and racial differences 13 ; accordingly, the profile of antibodies was determined qualitatively through measuring the mean index value of anti-Dsg 1 and 3. Besides, the considerably larger sample size of our study could confirm the findings of the previous studies with a high level of significance. Since the data were collected retrospectively, DIF study and its correlation with antibodies' profile have not been evaluated.
Further investigations of pathological features such as the presence of inflammatory and acantholytic dyskeratotic cells, as well as considering the severity of disease at the time of the presentation, are highly recommended in future studies.
Taken together, the overall agreement of these two diagnostic tools for PV and PF (ie, pathological assessment of the location of acantholysis and ELISA value of anti-Dsg 1, 3) was 89.97% in the present study. Although this correlation is significant, it is not perfect and some patients may have discordant results. In these cases, it is not known which diagnostic tools should be relied on most. The array of clinical, pathological, and serological findings and following up the course of the disease may be complementary to each other.

CO N FLI C T O F I NTE R E S T
The authors declare no conflict of interest.

E TH I C A L A PPROVA L
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
For this type of study, formal consent is not required.