False-Negative Rate of Direct Immunofluorescence on Lower Extremities in Bullous Pemphigoid

Am J Dermatopathol. 2021 Jan 1;43(1):42-44. doi: 10.1097/DAD.0000000000001710.


Bullous pemphigoid (BP) is the most common autoimmune blistering disorder of the skin. It is typified by tense blisters with a subepidermal split and mixed dermal inflammatory infiltrate on histology. Biopsy of the perilesional skin for direct immunofluorescence (DIF) has become the gold standard in the diagnosis of BP. Currently there is a pervasive clinical opinion that the lower extremity is a site with a high false-negative rate (FNR) for DIF in the diagnosis of BP. This notion is primarily based on 2 early studies from the 1980s without more recent confirmatory studies. To readdress this question regarding the lower extremities, a retrospective study from 2012 to 2018 was performed in our institution that evaluated the FNR of DIF by an anatomical site in the diagnosis of BP. Cases of BP were identified using standard criteria (clinical and histological data reviewed in cases with negative DIF), and overall, 79 patients were included in the study. A total of 4 false-negative DIF biopsies were verified. Two negative DIF were from the lower extremity yielding a FNR of 10% compared with 4% on the trunk and 3% from the upper extremity, with no statistically significant difference by anatomical sites. Our study fails to demonstrate a high FNR of DIF from the lower extremity in the diagnosis of BP.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / analysis*
  • Biomarkers / analysis
  • Biopsy
  • Complement C3 / analysis*
  • Databases, Factual
  • False Negative Reactions
  • Female
  • Fluorescent Antibody Technique, Direct*
  • Humans
  • Immunoglobulin G / analysis*
  • Infant
  • Lower Extremity
  • Male
  • Middle Aged
  • Pemphigoid, Bullous / diagnosis*
  • Pemphigoid, Bullous / immunology
  • Pemphigoid, Bullous / pathology
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Skin / immunology*
  • Skin / pathology


  • Autoantibodies
  • Biomarkers
  • C3 protein, human
  • Complement C3
  • Immunoglobulin G