New Treatments, Diagnostic Strategies in Bullous Diseases: Donna Culton, MD

Persistent, intensely itchy rashes in older adults are often written off as eczema or simple irritation, but they may signal serious autoimmune blistering diseases such as pemphigus or bullous pemphigoid, says Donna Culton, MD, professor of dermatology, University of North Carolina at Chapel Hill. As new targeted therapies like rituximab and dupilumab transform the treatment landscape, Culton emphasizes that early recognition, biopsy with direct immunofluorescence, and careful attention to comorbidities are crucial to getting patients on safer, more effective care.

This transcript was lightly edited; captions were auto-generated.

Transcript

Bullous diseases can be challenging to diagnose. What key clinical or diagnostic clues do you rely on to differentiate between subtypes?

Bullous disease is classically defined by having a blister, a bullae. They can be small vesicles or larger bullae, and that is the hallmark clinically for recognizing these diseases. But I think across both pemphigus and pemphigoid, we're starting to see more nonbullous presentations, specifically in pemphigoid. One of the things that I use a lot is any erosions on the skin—and especially in patients over, say, [age] 60 or 65—any itchy rash, especially itchy rashes that are not responding to topical steroids, need to be thinking that it could be a nonbullous presentation, especially a pemphigoid, and really doing the direct immunofluorescence to confirm the diagnosis.

Itch is a big factor in pemphigoid, so that's one of the things I use to distinguish them. But ultimately, the differentiation between pemphigus and pemphigoid relies clinically on how deep the blister is, so tense blisters being more pemphigoid [and] flaccid blisters being more pemphigus. But again, some of that goes out the window if there are no blisters. Then it really relies on biopsy for routine histology and direct immunofluorescence.

How has the emergence of new therapies changed your approach to managing patients with bullous diseases?

Yeah, it's a really great question. It's an exciting time in blistering disorders, where we have new medications. Finally, we have FDA-approved medications for the treatment of these diseases. For pemphigus, the first-line treatment that most people are doing is rituximab, especially for moderate to severe disease. That's kind of a big-gun medication that not all dermatologists are used to using. The main thing that we know, though, is that the earlier you treat a pemphigus patient with rituximab, the better chance that patient has to go on to a long-term, durable remission. For general dermatologists out there, even primary care physicians that suspect their patient may have pemphigus, get them to someone to either make the diagnosis themselves or get them to someone who can make the diagnosis so that ultimately, we can get them on treatment sooner.

For pemphigoid, we used to have only really toxic treatments to offer our elderly patients with pemphigoid. Now, with FDA approval of dupilumab, we have something that's safer, and it really does change the risk-benefit ratio of starting a systemic medication and one that's really targeted to the pathophysiology of the disease. And so a lot of us now are using dupilumab first line for the treatment of pemphigoid, again moderate to severe, but maybe even more milder forms, specifically in patients who are failing topical steroids.