Bullous Pemphigoid: A 10-Year Study of Discordant Results on Direct Immunofluorescence

Bullous pemphigoid (BP) is the most common subepidermal autoimmune disorder characterized by tense bullae. It is associated with circulating autoantibodies against BP antigen-1 and BP antigen-2. Diagnosis is based upon clinical, histopathologic, and immunopathologic examination. Direct immunofluorescence (DIF) of perilesional skin highlights C3 with or without IgG in a linear pattern along the basement membrane.

We hypothesized that repeat biopsies may be required for a definitive DIF diagnosis of BP, as initial DIF evaluation may result in a false-negative result.

A retrospective chart review was conducted on 1143 specimens collected for evaluation for BP. Cases from 2 Vancouver Coastal Health Authority laboratories from 2006 to 2016 were reviewed. Results were interpreted as positive, negative, or indeterminate based on pathologic description and specimen quality.

After meeting the inclusion criteria, 739 specimens were further evaluated. There were 289 cases of BP in the 10-year period. Five patients (1.73%; 95% confidence interval [CI], 1.50-1.96) required a second biopsy to support a BP diagnosis, and within this group, 1.04% of the 289 (95% CI, 0.811-1.27) were true successive negative-to-positive DIF results.

DIF is the most reliable test used to diagnose BP; however, a small percentage of patients will initially have a negative result. False-negative or indeterminate results may be due to specimen sampling from lesional skin or due to a subthreshold quantity of immune complexes in the skin. Repeat biopsy is warranted despite an initial negative DIF if BP is clinically suspected.