Why Immunology Now Drives the Conversation
Recording live at Elevate Summer in San Diego, host Eileen Cheever, PA-C and her guest Dr. James Song opened by framing how dermatology has moved past treating only what clinicians see on the skin. Song recalled training in reaction patterns and morphology — grouping diagnoses as papulosquamous, vesiculobullous, dermal, and so on — and noted that while useful to a point, morphology carries no implications for treatment. Two conditions in the same morphologic group can be treated completely differently.
The underlying immune pathway, Song explained, doesn't care what a disease looks like clinically. That reframe explains how two seemingly unrelated conditions — he cited CSU and AD — can share immune pathways and respond to the same medication. He and Cheever agreed the field is heading toward precision, predicting which medication a patient will respond to based on immunology rather than appearance.
Both reflected on how recently clinicians were throwing broad, non-targeted therapies at atopic patients simply to get them better. Song pointed out that in training, you could have a safe medicine or an effective medicine but not both — cycling patients from cyclosporine or prednisone to mycophenolate or methotrexate. With targeted therapies, he said, clinicians can now have efficacy and safety without compromising either.
What Type II Inflammation Actually Means
Song cautioned against loose terms like 'immune dysregulation' and offered a more precise framework: categorize inflammation by the cytokines involved, the immune cells producing them, the purpose of that arm of the immune system, and what diseases arise when it goes awry. Blocking the Type I pathway (antiviral defense) can bring out herpes; blocking Type III can bring out yeast. Too much Type I or III drives conditions like RA, thyroid disease, IBD, and psoriasis.
Type II, Song said, 'sits right in the middle' and probably makes up the largest swath of diseases dermatology providers treat. It evolved to fight parasitic infections, and when overactive it causes many of the conditions clinicians see daily.
Cheever added her own teaching device: Type II inflammation is a mix of innate and adaptive immunity — 'innate, immediate; adaptive, after.' She described innate immunity (mast cells, basophils, eosinophils) as the castle's moat and wall — immediate, non-specific, no memory — and adaptive immunity (T cells, B cells) as the trained, specific knights that arrive later and remember. Song layered on the evolutionary 'caveman' analogy: Type II once kept us alive against venom and parasites, but with those threats now rare, the pathway has become protective yet 'a little bit dramatic.'
The Key Cytokines and How They Work Together
Song named the canonical Type II cytokines — IL-4, IL-5, IL-13 — with IL-31 considered Type II-adjacent but placed in the same bucket. He explained the shift from 'TH2' to 'Type II' nomenclature reflects the inclusion of innate lymphoid cells alongside the adaptive arm. These cytokines have overlapping but distinct functions.
IL-4, Song said, is the only classic Type II cytokine thought to be an upstream regulator — the spark that starts the cascade, driving naive T cells to become TH2 cells. Those TH2 cells then produce IL-13, IL-31, and more IL-4, an autocrine effect Song compared to wind feeding a wildfire. Blocking IL-4 brings down IL-13 and IL-31 as well. The cytokines also cooperate on itch, skin barrier dysfunction, and immune cell recruitment.
Cheever and Song discussed IL-13's primary role in peripheral tissue—keratinocytes, fibroblasts, and epithelial tissue—and data suggesting IL-13 may set the stage in non-lesional AD skin. IL-4, by contrast, acts on peripheral tissue and on central hematopoietic immune cells. They also touched on fibroblasts, periostin, and neurogenic sensitization feeding the itch-scratch cycle, noting these processes happen interchangeably rather than as neat, stepwise dominoes.
Comorbidities: Feeding Several Birds With One Scone
Song walked through the atopic march — atopic dermatitis followed by allergic rhinitis, asthma, food allergies — stressing that skin disease doesn't exist in a vacuum. He raised the window-of-opportunity concept: because sensitization for asthma or EoE may begin transcutaneously at the skin, restoring and repairing the skin with effective AD therapy could potentially affect disease course. Nearly every EoE patient, he noted anecdotally, carries an atopic comorbidity. He shared a patient who, after AD treatment, told him they could taste food and no longer feared food getting stuck in their throat.
Both emphasized connecting the dots for patients — asking about wheezing, mouth breathing, food getting stuck, reflux — which takes little time but signals buy-in and builds trust. Song also flagged comorbidities that are downstream effects of poorly controlled AD rather than direct Type II drivers: anxiety, depression, ADHD, and impaired growth and bone health.
Song cited dupilumab data presented recently in children on the lower side of the growth curve, where about a third achieved at least 5% growth in height, with over 50% of that maintained through 52 weeks of follow-up — data he shares with on-the-fence parents. He also referenced a study showing significant reductions in neuropsychotropic medication use, including methylphenidate, among dupilumab-treated patients. Cheever, a parent of a daughter with eczema, said she has seen the difference in attention and anxiety firsthand.
Redefining Treatment Success — and What's Next
As treatments improve, Song said, expectations and guidelines evolve with them. While EASI-75/90 and NRS metrics have their place, his bottom line is restoring function and quality of life regardless of the exact score. His favorite screening question: Is there anything your eczema is keeping you from doing that you normally would? Cheever offered her own barometer — teenage patients arriving in long hoodies and sweatpants on hot, humid New England days who later return in T-shirts and shorts, no longer hiding their skin.
On documentation, Song favors photographs and recommends at minimum charting IGA, BSA, and NRS — useful for drug approvals and tracking progress. Cheever is an enthusiastic 'photos, photos, photos' advocate for both clinical tracking and patient engagement.
Looking ahead, Song described two parallel paths: better diagnostic tools such as gene expression profiling to predict medication response (though he said these still need validation on sensitivity and positive predictive value), and new pipeline therapies. Despite recent failures, including the OX40 agents, he sees promise in more selective, higher-potency, longer-half-life agents; combined or synergistic targets (IL-4 with IL-31, IL-22, TSLP, or psoriasis pathways like IL-17); oral agents targeting previously 'undruggable' transcription factors; and immunorestorative approaches involving T-reg cells aimed at homeostasis rather than simply blocking a cytokine. Cheever framed the shift as moving from phenotype to endotype — translating each patient's biologic features into targeted therapy.