Utility of immunohistochemistry for immunoglobulin G4 in the diagnosis of pemphigus

Objectives: Direct immunofluorescence (DIF) is the diagnostic gold standard for pemphigus. However, it is limited by the requirement of additional fresh-frozen tissue, immediate processing, and availability of a fluorescent microscope. The present study aims to assess the role of immunoglobulin G4 (IgG4) immunohistochemistry (IHC) on formalin-fixed paraffin-embedded tissue for the diagnosis of pemphigus by comparing IgG4-IHC results to DIF. Materials and Methods: IgG4-IHC was performed on formalin-fixed paraffin-embedded sections of lesional and perilesional skin biopsies of 30 cases of DIF-proven pemphigus and 30 non-pemphigus controls. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were analyzed for IgG4-IHC on lesional and perilesional biopsies to compare their diagnostic significance. Statistical analysis: Data were analyzed using the Statistical Package for the Social Sciences version 29. Sensitivity, specificity, PPV, NPV, and diagnostic accuracy of IgG4-IHC were calculated using standard formulae. Receiver operator curve analysis was performed for IgG4-IHC in lesional and perilesional skin to compare their diagnostic significance. The youden index was calculated using the formula “sensitivity + specificity – 1.” P < 0.05 was considered statistically significant. Results: Out of 30 cases enrolled for the study, 26 (86.6%) were diagnosed as pemphigus vulgaris and four (13.4%) as pemphigus foliaceous. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of IgG4-IHC for pemphigus on lesional biopsy were 66.7%, 100%, 100%, 75%, and 83.3% while the sensitivity, specificity, PPV, NPV, and diagnostic accuracy for the perilesional biopsy were 56.7%, 100%, 69.8%, and 78.3%, respectively. Conclusions: Our study indicated that IgG4-IHC is highly specific, but not sufficiently sensitive to replace DIF to diagnose pemphigus. IgG4-IHC on lesional skin is likely to be particularly valuable in a setting where a frozen section or immunofluorescence facility is not available. Further studies on larger samples are warranted to validate the role of IgG4-IHC in pemphigus.