Clinicians Explore Type 2 Inflammation Across Dermatologic Diseases

Marshall J. Shuler, MD, FAAD, led a recent Dermatology Times Case-Based Roundtable in Charlotte, North Carolina, examining the role of type 2 inflammation across several dermatologic diseases. The September 28, 2026, discussion used patient cases to explore how shared inflammatory pathways may connect seemingly distinct conditions, including atopic dermatitis (AD), prurigo nodularis (PN), chronic spontaneous urticaria (CSU), and bullous pemphigoid (BP).

Throughout the program, Shuler encouraged attendees to look beyond visible disease severity and consider itch, sleep disruption, psychosocial burden, comorbid atopic disease, patient preferences, and the underlying inflammatory pathway when individualizing treatment.¹

Pediatric AD Case Highlights Burden Beyond Body Surface Area

The first case involved a 10-year-old boy with moderate AD since early childhood and approximately 15% body surface area involvement. Despite the seemingly moderate extent of his disease, he had stopped participating in soccer because of itching and visible lesions, scratched during the night at least 5 nights per week, and was developing anxiety about his appearance. His height was also at the 25th percentile and slightly below expectations based on parental height.¹

When Shuler asked attendees to characterize the patient's disease, the group viewed the case as severe because of its effect on sleep, emotional well-being, and daily activities rather than relying on body surface area alone.

“Maybe body surface area is moderate, but that's a severe significant impact,” Shuler said.

The discussion emphasized asking patients and families directly about itching, sleep, school, sports, and other aspects of daily life. Shuler also connected sleep disruption with pediatric growth, discussing evidence suggesting that improved disease control may allow children with AD to experience catch-up growth.

The case also prompted discussion of the “atopic march” and whether earlier control of type 2 inflammation could potentially affect the trajectory of other atopic conditions. Attendees described counseling families about the connections among AD, asthma, food allergy, and other manifestations of atopy.

When considering treatment escalation, the group identified persistent itch, sleep disruption, emotional distress, social impairment, inadequate response to topical therapy, and patient or family preference as important factors. Shuler emphasized that the ultimate treatment goal was not simply improving the results of the skin examination.²

“Get him to play soccer again. Go out, have his friends, not be worried about his skin, and let him sleep,” he said.

Patient Preference Shapes Systemic AD Treatment

The pediatric case transitioned into a broader discussion about choosing systemic treatment for AD. Attendees discussed Dupixent as a potential option for the patient, while also considering how the decision could change with age, needle aversion, vaccination status, and the availability of oral Janus kinase (JAK) inhibitors.

Several clinicians said they would generally favor dupilumab before a JAK inhibitor in an eligible pediatric patient, although the group stressed that there was no single approach appropriate for every patient.

The discussion also highlighted a practical barrier that may be overlooked when prescribing biologics: Some patients are not necessarily afraid of receiving injections but are uncomfortable administering injections themselves.

Shuler encouraged clinicians to provide hands-on education and support during the first injection rather than assuming patients will become comfortable with administration on their own. Attendees described bringing patients back within approximately 4 to 6 weeks after initiation to assess response, reinforce treatment adherence, and troubleshoot pharmacy or administration issues.²

Clinicians also debated when an inadequate response should prompt a change in therapy. Persistent pruritus, continued sleep disruption, and breakthrough disease were cited as signs that treatment might not be providing sufficient control. Some attendees said they would consider changing treatment after approximately 3 months with no improvement, whereas others were willing to allow as long as 6 months depending on the degree of response and individual circumstances.

PN Case Centers Itch and Quality of Life

The second major case involved a 50-year-old woman with a 3-year history of intensely pruritic nodules on the arms, legs, and back. She experienced excoriations, scarring, sleep disruption, and embarrassment over others asking about her visible lesions. Previous treatments included topical corticosteroids, oral antihistamines, gabapentin, and phototherapy, without adequate disease control.

Shuler emphasized that PN should not simply be viewed as more severe AD. Instead, the discussion focused on the interaction between the immune system and nerve fibers and the role of cytokines, including IL-4, IL-13, and IL-31, in pruritus.

Attendees debated how they select between dupilumab and nemolizumab in PN. Several clinicians said the patient's predominant symptoms and comorbidities would influence their decision.

For patients whose primary complaint is severe itch without substantial additional manifestations of atopy, some attendees favored nemolizumab. Conversely, clinicians said they might lean toward dupilumab when PN occurs alongside AD, asthma, or other manifestations potentially related to type 2 inflammation.¹

One attendee explained that the broader clinical picture matters when selecting therapy because many patients have already experienced prolonged disease and multiple unsuccessful treatments.

“I don't want to play with my patient's quality of life, because by the time that they're coming to us, they've been suffering for a long time,” the clinician said.

The group also discussed off-label JAK inhibitor use in difficult-to-treat PN, with some attendees describing rapid improvements among patients who had not responded adequately to other therapies. However, treatment decisions remained centered on individual disease characteristics, safety considerations, and quality-of-life burden.²

Expanding Options Change the CSU Treatment Conversation

The roundtable next turned to CSU and the central role of mast cell activation. Shuler reviewed how IgE- and IgG-mediated pathways can contribute to mast cell degranulation and discussed the clinical characteristic of wheals appearing and resolving in different locations over approximately 24 hours.

The case involved a 44-year-old patient with daily hives accompanied by perioral involvement and lip swelling. The patient had achieved only partial control despite multiple medications, including antihistamines and intermittent prednisone tapers.

Shuler encouraged attendees to distinguish spontaneous disease from chronic inducible urticaria by asking patients whether they recognize reproducible triggers for their symptoms. The group then discussed advanced treatment options, including omalizumab, dupilumab, and remibrutinib.

Shuler noted that omalizumab had historically been an option he would refer patients to an allergist to receive, whereas newer therapeutic options have expanded what dermatology clinicians can offer directly. He reviewed differences in therapeutic targets, noting omalizumab's targeting of IgE and remibrutinib's inhibition of Bruton tyrosine kinase.

The discussion around remibrutinib also focused on safety counseling, particularly bleeding and petechiae. Shuler explained that these effects relate to platelet function rather than platelet count, meaning a complete blood count would not necessarily identify the underlying functional change.

Across therapies, clinicians stressed the importance of explaining expected response timelines and moving beyond antihistamines when adequate disease control is not achieved.

Type 2 Inflammation Extends to BP

The final portion of the discussion explored BP and how a disease traditionally recognized for autoantibodies at the basement membrane can also involve type 2 inflammatory pathways.

Shuler discussed the presence of both IgG and IgE in BP and connected IL-4 activity with antibody production and the broader type 2 inflammatory response. Attendees shared generally positive experiences with dupilumab in BP, particularly as a steroid-sparing strategy, while acknowledging that response may take time.

Shuler compared the delayed response with other therapies that affect antibody production, emphasizing that existing antibodies and antibody-producing cells do not disappear immediately after a pathway is targeted.

The discussion illustrated the central theme of the roundtable: Diseases that appear clinically distinct may share inflammatory mechanisms that can inform therapeutic decision-making.

Across the AD, PN, CSU, and BP cases, attendees emphasized that selecting therapy requires more than identifying a diagnosis or measuring visible disease. Sleep, itch, psychosocial effects, comorbid disease, treatment preferences, administration burden, response speed, and safety all influence what constitutes the appropriate therapy for an individual patient.

Shuler encouraged clinicians to recognize type 2 inflammation not simply as an immunologic concept, but as a framework that may help identify connections between diseases and guide more individualized treatment decisions.

References

1. Chovatiya R, Hawkes JE, DiRuggiero D, Pansch LA, Simcox E, Gonzalez T. Type 2 inflammation and its role in dermatologic diseases. Int J Dermatol.2025;64(6):978-991. doi:10.1111/ijd.17707
2. Paller AS, Siegfried EC, Thaçi D, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol.2020;83(5):1282-1293. doi:10.1016/j.jaad.2020.06.054