In this episode of Topical Conversations, Dr. Michael Cameron and Dr. Graham Litchman explore the pathophysiology of type 2 inflammation in dermatologic diseases and discuss how evolving treatment options are reshaping clinical practice. From atopic dermatitis (AD) and prurigo nodularis (PN) to chronic spontaneous urticaria (CSU), they break down the mechanisms of disease, targeted therapies, and emerging treatment strategies that are changing the way dermatologists approach inflammatory skin conditions. 

Understanding type 2 inflammation across dermatologic diseases 

Since the approval of dupilumab in 2017, research into type 2 inflammation has expanded dramatically. Dr. Litchman highlights how this shared inflammatory pathway connects conditions such as asthma, allergic rhinitis, AD, PN, and CSU, allowing dermatologists to educate patients on the systemic nature of their disease. 

Dr. Cameron emphasizes the complex immune dysregulation in type 2 diseases, particularly the cross-talk between inflammatory cells. He explains that IL-4 and IL-13, key drivers of AD and PN, are present not only on inflammatory cells but also on sensory nerves, contributing to chronic itch. Targeted therapies like dupilumab, tralokinumab, lebrikizumab, and nemolizumab work by interrupting these signaling pathways, leading to symptom relief. 

Emerging therapies and novel mechanisms of action 

The discussion shifts to next-generation treatments that go beyond blocking cytokine communication to directly targeting inflammatory cells. Dr. Litchman shares excitement about the potential of Bruton’s tyrosine kinase (BTK) inhibitors that prevent mast cell activation and degranulation; JAK1 inhibitors that have the potential to expand options for systemic inflammatory control; monoclonal antibodies that look to directly inhibit IL-5, IL-13, and eosinophils, offering new avenues for treatment; and OX40 ligand inhibitors, that work by eliminating pathogenic T cells rather than just blocking their signals. 

Dr. Cameron highlights key priorities in drug development, including longer dosing intervals (every 3 months), higher efficacy (bispecific and trispecific antibodies), and more oral treatment options. 

The role of dermatologists in managing CSU and PN 

CSU is often referred out, but both doctors agree that dermatologists should reclaim these patients. Dr. Cameron points out that many patients with CSU patients are also atopic, reinforcing that dermatologists are well-equipped to manage their care. With BTK inhibitors and anti-c-Kit therapies emerging, now is the time to bring CSU management back into dermatology practices. 

For PN, the approval of dupilumab and nemolizumab has been a breakthrough. Previously neglected due to a lack of therapeutic options, patients with PN now have access to effective, targeted treatments. Dr. Cameron emphasizes that many patients with PN also have coexisting atopic conditions, making these therapies beneficial beyond PN alone. 

Key takeaways: 

• Type 2 inflammation plays a central role in several dermatologic conditions, including atopic dermatitis, prurigo nodularis, and chronic spontaneous urticaria 
• Emerging treatments, including BTK inhibitors, JAK1 inhibitors, and OX40 ligand inhibitors, offer new approaches by targeting inflammatory cells directly rather than just blocking cytokines 
• Prurigo nodularis treatment has advanced, with new options providing effective options for a previously difficult-to-manage condition 
• It is crucial that dermatologists remain informed about new mechanisms of action to optimize individualized patient care as treatment options expand