Bullous Pemphigoid: The Time to Treat Is Now, Fall Clinical Speakers Say

Earlier recognition of bullous pemphigoid (BP) is critical but safer, targeted treatment options are emerging for this aging and medically fragile patient population, according to a presentation from Donna Culton, MD, PhD, and Prince Adotama, MD, at the 2025 Fall Clinical Dermatology Conference.

Bullous pemphigoid has long been characterized by tense, itchy blisters, but up to 20% of patients never develop bullae. These non-bullous cases, often presenting with urticarial plaques, eczematous patches, or isolated pruritus, are easily missed, especially in elderly patients.

Dr. Culton emphasized this with a clinical case: a 79-year-old man with diabetes and renal cell carcinoma, undergoing treatment with nivolumab, presented with a 2-month history of pruritic plaques without blisters. Despite lacking the classic clinical morphology, he was ultimately diagnosed with BP—illustrating the need for heightened diagnostic suspicion.

“These patients can go undiagnosed for months,” Dr. Culton said. “If you see an older patient with persistent pruritus—even in the absence of bullae—BP must remain on your differential.”

BP is caused by autoantibodies targeting hemidesmosomal proteins BP180 and BP230, disrupting dermal-epidermal adhesion and triggering inflammation. Traditional teaching focuses on IgG-mediated complement activation, leading to eosinophil recruitment and blister formation.

However, Drs. Culton and Adotama highlighted the underappreciated role of IgE. Although not routinely tested via direct immunofluorescence, IgE antibodies against BP180 are present in up to 85% of patients and are strongly correlated with disease severity and eosinophilia.

“We’ve historically thought of this as an antibody-blister disease,” Dr. Culton said. “But what’s in between is increasingly clear: this is a type 2 inflammatory disorder, with overexpression of IL-4, IL-5, and IL-13, paralleling diseases like atopic dermatitis.”

Diagnosis requires a multimodal approach, they said:

• Histopathology (H&E biopsy) may show subepidermal splitting with eosinophils, but this is often absent in non-bullous forms.
• Direct immunofluorescence (DIF) remains the gold standard, showing linear IgG and/or C3 deposition at the basement membrane in both bullous and non-bullous BP.
• Serologies, including indirect immunofluorescence and ELISA for BP180 and BP230 (IgG and IgE), provide supporting evidence.

Initial treatment of moderate-to-severe BP often involves high-potency topical steroids or systemic corticosteroids, despite known adverse effects—especially in elderly patients with diabetes, hypertension, or renal insufficiency.

“Steroids work. They're fast, they’re cheap, but they're risky,” Dr. Culton said. “For many patients, particularly the medically fragile, we must consider steroid-sparing therapies early.”

She outlined common adjunctive agents, including: doxycycline plus niacinamide; methotrexate; azathioprine; and mycophenolate mofetil.

Still, the doctors emphasized that many of these are immunosuppressive and may not be appropriate for older patients with malignancy, infection risk, or multi-organ comorbidities.

Biologic therapies are redefining treatment, however, as the doctors noted:

Dupilumab (IL-4/IL-13 inhibition)

• 53% of patients achieved remission by 24 weeks, increasing to 95% by one year.
• Steroid use dropped by 81%.
• Patients with cutaneous-only disease and shorter disease duration (<8 months) responded best.
• Safety profile was favorable with low rates of adverse events.

Omalizumab (IgE inhibition)

• Slower response (median 6.6 months to remission), but effective in IgE-predominant disease.
• Decreases in eosinophilia and urticaria observed.
• Most effective as adjunctive therapy; monotherapy alone insufficient in moderate to severe cases.

Rituximab (CD20 B-cell depletion)

• 75% of patients achieved remission in retrospective studies.
• Time to response longer (5–6 months), but effective even in severe cases.
• Higher relapse rate (up to 20%) compared to dupilumab.
• Infection risk, particularly in immunocompromised patients, remains a concern.

Across those three biologics, remission rates were similar, the doctors said, but time to response and relapse risks varied. Dupilumab showed the most rapid and sustained control with the best safety profile—making it a favored option in elderly or medically complex patients.

The speakers emphasized a patient-centric, risk-adjusted approach, taking into account:

• Disease duration and severity
• Presence or absence of mucosal involvement
• Serologic markers (especially BP180 IgE)
• Comorbidities, malignancy, infection risk
• Patient preferences and access to therapy

 “It’s a great time to be treating BP,” Dr. Adotama said. “We finally have options that allow us to balance efficacy with safety.”