Clinical, Serologic, and Histopathologic Features of Patients with Pemphigus with either Positive or Negative IgG4 Intercellular Deposition by Direct Immunofluorescence: A Retrospective Case-Control Study of 55 Cases

Summary: BACKGROUND: Intercellular IgG4 deposition is variably present on DIF in patients with pemphigus. Whether this feature has clinical, serologic, or histopathologic correlates was unknown. METHODS: We identified patients with pemphigus with DIF reports showing intercellular IgG, IgG4, and/or C3 deposition (8/22/2017-11/30/2023) and stratified them by intercellular IgG4 status. Clinical and serologic data were extracted from electronic records. Corresponding biopsy slides were reviewed for histopathologic findings. RESULTS: Of 55 patients meeting inclusion criteria, 52 (94.5%) had intercellular IgG deposition and 42 (76.4%) had intercellular IgG4 on DIF. Compared to the IgG4-negative group, the IgG4-positive group was significantly more likely to have had a vesiculobullous lesion biopsied (p=0.024), serum anti-desmoglein 1/3 antibodies detected by ELISA (p=0.004 and p=0.006, respectively), serum anti-intercellular surface antibodies demonstrated by indirect immunofluorescence (p=0.006), and acantholysis (p=0.019) or lack of lichenoid inflammation (p=0.0004) observed on histopathology. Paraneoplastic pemphigus (PNP) was more frequent in the IgG4-negative group (p=0.009). CONCLUSION: In patients with pemphigus and intercellular IgG on DIF, absence of IgG4 intercellular deposition should prompt consideration of PNP. Because DIF IgG4 status correlated with the likelihood of detecting circulating desmoglein antibodies or observing certain microscopic features including lichenoid inflammation and acantholysis, further studies should explore whether IgG4-negative pemphigus represents a distinct disease variant.