Dr. Donna Culton discusses the latest on the diagnosis and treatment of autoimmune blistering disorders.
Donna A. Culton, MD, PhD, is Associate Professor of Dermatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
“One of the biggest challenges in the diagnosis of immunobullous disease is the recognition of atypical clinical presentations of pemphigus and pemphigoid. While the clinical findings may not be classic, the direct immunofluorescence will confirm the diagnosis,” said Donna A. Culton, MD, PhD, who presented on autoimmune blistering disorders at Maui Derm PA+NP 2022.
The diagnosis of autoimmune blistering disorders depends on the clinical evaluation, as well as biopsies for both hematoxylin and eosin (H&E) and direct immunofluorescence. After those evaluations confirm the diagnosis, dermatologists can feel comfortable moving onto some of today’s more targeted treatments, said Dr. Culton, who directs the Autoimmune Blistering Disorder Clinic and Clinical Immunofluorescence Laboratory at the University of North Carolina at Chapel Hill.
Therapeutic Innovations
Long used immunosuppressive steroid-sparing agents, including prednisone, azathioprine, mycophenolate, and methotrexate, used to be the go-to treatments for pemphigus and pemphigoid, according to Dr. Culton.
“The innovations in treatment are really a reflection of our increased understanding of the pathophysiology of both pemphigus and pemphigoid. Even though they are similar in that they are antibody-mediated blistering disorders of the skin, they really are quite different in their underlying pathophysiology.”
Targeting B lymphocytes is now a well-established treatment avenue, with rituximab becoming the first FDA-approved treatment for pemphigus vulgaris. Rituximab showed strong efficacy in the treatment of pemphigus in clinical trials, according to Dr. Culton.
“The limitation is that there is no specificity to autoreactive B cells. All the B lymphocytes are depleted with rituximab and other B cell depleting agents.”
Still, the success of rituximab as a targeted therapy in pemphigus led to a number of clinical trials looking at new targets for treating pemphigus and pemphigoid, she said.
There are new cell therapy treatments in clinical trials that would allow for depletion of only the autoreactive B cells in pemphigus, said Dr. Culton.
“… autoantibodies are really what induce autoimmune blistering disorders. We’ve used intravenous immunoglobulin (IVIG) as a therapy for many years. Now what we’re seeing is that there are other ways to target antibodies that rely on the neonatal IgG Fc receptor (FcRn). It’s a new focus for us—a new drug target that really is specific to the autoimmune process, itself, which is exciting.”
These treatments are being trialed in both pemphigus and pemphigoid.
Yet another innovation targets the inflammatory cascade that occurs with pemphigoid, according to Dr. Culton.
“In addition to the autoantibodies being there, we know neutrophils and eosinophils specifically play a large role in the clinical manifestations and symptoms that patients experience. We’re starting to see more specific drug targets emerge in that regard.”
“The goal would be to maintain the efficacy of B cell depleting agents we currently have available, but with improved safety and less immunosuppression with preservation of healthy B cells. We have for a long time wanted better therapies that are less immunosuppressive and are finally moving in that direction,” she said.
Disclosures: Dr. Culton is a consultant and/or advisor to Argenx, Alkahest, Pincel, Kezar, and Janssen, and is a clinical trial investigator for Principia, Cabaletta, and Regeneron.
