Nonbullous pemphigoid: A systematic review

Abstract

Background: Bullous pemphigoid is an autoimmune disease that typically presents with tense bullae and severe pruritus. However, bullae can be lacking, a subtype termed nonbullous pemphigoid.

Objective: To summarize the reported characteristics of nonbullous pemphigoid.

Methods: The EMBASE and MEDLINE databases were searched using "nonbullous pemphigoid" and various synonyms. Case reports and series describing nonbullous pemphigoid were included.

Results: The search identified 133 articles. After selection, 39 articles were included, presenting 132 cases. Erythematous, urticarial plaques (52.3%) and papules/nodules (20.5%) were the most reported clinical features. The mean age at presentation was 74.9 years. Histopathology was commonly nonspecific. Linear depositions of IgG and/or C3 along the basement membrane zone were found by direct immunofluorescence microscopy in 93.2%. Indirect immunofluorescence on salt-split skin was positive in 90.2%. The mean diagnostic delay was 22.6 months. A minority of patients (9.8%) developed bullae during the reported follow-up.

Limitations: Results are mainly based on case reports and small case series.

Conclusion: Nonbullous pemphigoid is an underdiagnosed variant of pemphigoid that most often does not evolve to bullous lesions and mimics other pruritic skin diseases. Greater awareness among physicians is needed to avoid delay in diagnosis.

Keywords: autoimmune blistering disease; autoimmune bullous disease; bullous pemphigoid; characteristics; clinical presentation; nonbullous pemphigoid; systematic review; terminology.