When Bullous Pemphigoid Is Not Bullous Pemphigoid: The Importance of Going Beyond Direct Immunofluorescence

Bullous pemphigoid (BP) is the most common autoimmune bullous disease, but rarer forms of pemphigoid may appear identical to BP on routine histopathology and direct immunofluorescence (DIF). Here, we present the case of a 60-year-old man, who was initially thought to have BP, with supportive findings on routine histopathology and DIF. However, prominent oral involvement and cutaneous lesions refractory to conventional treatment suggested an alternate diagnosis. Further workup was performed, including indirect immunofluorescence (IIF) on salt-split skin, which showed binding of antibodies to the dermal floor rather than to the blister roof, and enzyme-linked immunosorbent assay for pemphigus and pemphigoid antibodies. With these additional tests, we concluded that the patient does not have BP but rather anti-p200 pemphigoid, anti-p105 pemphigoid, or a yet undiscovered form of pemphigoid. We reached a presumptive diagnosis of anti-p200 pemphigoid, as it is the most common pemphigoid with serum antibodies to the dermal floor of human salt-split skin by IIF. This case demonstrates that suspicion for other autoimmune bullous diseases in cases of treatment-refractory and clinically aberrant BP is essential. A limited workup may lead to a missed diagnosis and ultimately less efficient disease management.