Type 2 Inflammation Links AD, Prurigo, Urticaria and BP in Case Roundtable

A 10-year-old boy with roughly 15% body surface area involvement rated as severe — because itch kept him off the soccer field, not because of his lesion counts. That case anchored a Dermatology Times Case-Based Roundtable on September 28, 2026, in Charlotte, North Carolina, where Marshall J. Shuler, MD, FAAD, led clinicians through how type 2 inflammation connects atopic dermatitis (AD), prurigo nodularis (PN), chronic spontaneous urticaria (CSU) and bullous pemphigoid (BP).

Shuler pushed attendees to look past visible severity and weigh itch, sleep disruption, psychosocial burden, comorbid atopy and the underlying inflammatory pathway when individualizing therapy.

How severe is 'moderate' AD?

The pediatric case involved moderate AD since early childhood. The boy had quit soccer because of itching and visible lesions, scratched at night at least 5 nights per week and was developing anxiety about his appearance. His height sat at the 25th percentile, slightly below expectations based on parental height.

Attendees called the disease severe on that basis. "Maybe body surface area is moderate, but that's a severe significant impact," Shuler said. He tied sleep disruption to pediatric growth, citing evidence that better disease control may allow catch-up growth. He also raised the "atopic march" question — whether earlier control of type 2 inflammation could shift the trajectory toward asthma and food allergy.

Escalation triggers the group identified included persistent itch, sleep disruption, emotional distress, social impairment, inadequate topical response and family preference. "Get him to play soccer again. Go out, have his friends, not be worried about his skin, and let him sleep," Shuler said of the treatment goal.

What drives systemic AD therapy selection?

Attendees discussed Dupixent for the patient while weighing age, needle aversion, vaccination status and the availability of oral JAK inhibitors. Several clinicians favored dupilumab before a JAK inhibitor in an eligible pediatric patient, though no one claimed a single approach fits all.

One practical barrier drew attention: some patients don't fear injections but balk at self-administering them. Shuler advised hands-on education during the first injection. Attendees described bringing patients back within about 4 to 6 weeks to assess response, reinforce adherence and troubleshoot pharmacy issues.

On inadequate response, persistent pruritus, continued sleep disruption and breakthrough disease signaled insufficient control. Some attendees would switch therapy after roughly 3 months without improvement; others would wait up to 6 months depending on response and circumstances.

Prurigo nodularis: not just severe AD

The second case followed a 50-year-old woman with a 3-year history of intensely pruritic nodules on her arms, legs and back, plus excoriations, scarring, sleep disruption and embarrassment over visible lesions. Topical corticosteroids, oral antihistamines, gabapentin and phototherapy had all failed to control her disease.

Shuler stressed that PN isn't simply more severe AD. Discussion centered on immune–nerve interaction and cytokines including IL-4, IL-13 and IL-31.

Attendees split on dupilumab versus nemolizumab. For severe itch without much accompanying atopy, some favored nemolizumab; when PN coexists with AD or asthma, clinicians leaned toward dupilumab. "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," one attendee said. Some also described rapid improvements with off-label JAK inhibitors in difficult-to-treat PN.

What's changing in CSU?

A 44-year-old with daily hives, perioral involvement and lip swelling had reached only partial control on antihistamines and intermittent prednisone tapers. Shuler reviewed how IgE- and IgG-mediated pathways drive mast cell degranulation and noted wheals typically appear and resolve in different locations within about 24 hours.

He urged clinicians to separate spontaneous disease from chronic inducible urticaria by asking about reproducible triggers. Options discussed included omalizumab, dupilumab and remibrutinib. Omalizumab targets IgE; remibrutinib inhibits Bruton tyrosine kinase. Shuler noted he once referred patients to allergists for omalizumab, but newer agents have expanded what dermatologists can offer directly.

Remibrutinib counseling includes bleeding and petechiae. Shuler explained these effects involve platelet function rather than platelet count, so a complete blood count won't necessarily catch the change.

Does type 2 inflammation bridge to BP?

The final segment covered BP, where both IgG and IgE act on the basement membrane zone. Shuler linked IL-4 activity to antibody production within the broader type 2 response. Attendees reported generally positive dupilumab experience in BP, particularly as a steroid-sparing strategy, while acknowledging responses take time — existing antibodies and antibody-producing cells don't vanish once a pathway is targeted.

The throughline: distinct diagnoses can share mechanisms, and therapy selection should weigh sleep, itch, psychosocial effects, comorbidity, administration burden, response speed and safety. As dupilumab, nemolizumab and remibrutinib reshape options across these diseases, that framework is likely to guide more individualized decisions in dermatology clinics.