25/02/2026
There's a reason some people with eczema never fully respond to standard treatment - and once you understand it, everything starts to make sense.
For a lot of people, the usual approach works. Moisturise. Reduce inflammation. Protect the barrier. Done.
But for others - maybe you - it doesn't. And that's not a failure of willpower, or bad luck, or not trying hard enough.
It's because atopic dermatitis isn't one condition. It's two distinct pathologies that look identical on the surface but have completely different drivers underneath. And treating the wrong one is exactly why so many people stay stuck.
The Barrier-Driven Type
This is the one medicine understands well. The skin barrier - your body's physical wall against the outside world - is genetically weak. It can't hold moisture. It can't keep irritants out. Things get in, the immune system reacts, inflammation follows.
Treat the barrier. Calm the reaction. This approach works here.
The Immune-Driven Type
This is where things get more complex - and where conventional treatment consistently falls short.
In this type, the problem doesn't start at the skin. It starts with an immune system that is fundamentally dysregulated - specifically, a Th2-dominant immune response that has become hypersensitive and chronically overactive.
Here's what that actually means:
Your immune system is overproducing specific inflammatory chemicals called cytokines - particularly IL-4, IL-5, IL-13, and IL-31. These aren't just causing surface inflammation. They are actively suppressing production of your key barrier proteins: filaggrin, loricrin, and involucrin - the proteins responsible for holding your skin together.
So your barrier isn't weak because of genetics alone. Your barrier is being actively dismantled from the inside by your own immune response.
IL-5 specifically drives the production of eosinophils — specialised white blood cells associated with allergic inflammation. Elevated eosinophils on a blood test are one of the clearest signals that this immune-driven type is what you're dealing with.
Why Elevated Eosinophils Matter
Eosinophils aren't passive bystanders. When activated, they release toxic proteins - eosinophil-derived neurotoxin and eosinophil peroxidase - that directly damage your skin barrier. They create microscopic breaches that bacteria exploit. And paradoxically, despite being immune cells, they are ineffective at killing Staphylococcus aureus — the bacteria most commonly colonising eczema-affected skin.
Elevated eosinophils correlate with more severe atopic dermatitis, higher IgE levels, greater infection risk, and — critically — a better response to immune-modulating therapies rather than barrier repair alone.
The Spiral That Keeps People Stuck
Once immune dysregulation takes hold, a self-perpetuating cycle begins:
Overactive Th2 immune response → IL-4, IL-5, IL-13 released → barrier proteins suppressed → skin barrier breaks down → Staphylococcus aureus enters and colonises → bacteria form biofilms → immune system escalates response → eosinophils activated → more barrier damage → more bacterial entry → cycle repeats.
This is why short courses of antibiotics fail. A 7-day course kills surface bacteria. It does not pe*****te biofilms - protective bacterial colonies that are up to 1000 times more resistant to antibiotics than free-floating bacteria. When the antibiotics stop, the biofilm releases its colonies and reinfection follows. Minimum 14-21 days is typically required just to begin disrupting biofilm structure.
The Cell Danger Response - Why It Never Fully Resolves
Your body has a built-in healing sequence called the Cell Danger Response. It runs in three phases: defend against the threat, repair the damage, then resolve the inflammation and return to baseline.
In chronic immune-driven atopic dermatitis, this sequence gets interrupted. The body never reaches phase three. It stays locked in defence mode - perpetually sensing danger, perpetually inflamed, perpetually reactive.
Think of it as an oversensitive alarm system where the original event set the sensitivity so high that almost anything triggers it now - cold air, chlorinated water, soap, humidity changes, airborne chemicals, even physical friction.
Why Environment Hits This Type So Hard
Your immune system doesn't just react to pathogens. It reacts to multiple categories of signals: (Here's two)
DAMPs - Damage-Associated Molecular Patterns - triggered by things like chlorine in water, dry cold air, chemical exposure, and physical trauma to the skin.
PAMPs - Pathogen-Associated Molecular Patterns - triggered by bacteria like Staphylococcus aureus.
In immune-driven atopic dermatitis, Pattern Recognition Receptors on your skin cells are chronically upregulated. They are scanning constantly. The threshold for triggering a full immune response is extremely low. This is why environmental factors that wouldn't affect most people - indoor heating dropping humidity below 30%, formaldehyde off-gassing from furniture, VOCs from cleaning products, hard water with elevated chloramine - can send the skin into a flare. Every one of these is being read by your immune system as a threat signal.
What This Changes About Treatment
If your atopic dermatitis is immune-driven - elevated eosinophils, recurring infections, diminishing returns on steroids, failure to respond to barrier repair - then the treatment approach needs to shift fundamentally.
Barrier repair still matters. But it cannot lead. Because your immune system will continue breaking that barrier down faster than any topical can rebuild it.
What needs to happen simultaneously:
Immune modulation - calming the Th2 overresponse.
Nutrients I commonly prescribe include perilla, quercetin, omega-3 fatty acids (high ratio of DHA to EPA, not the other way around like most supplements), vitamin D and zinc and here's why.
Perilla is the most potent natural eosinophil suppressor available. It potently inhibits IL-5 production at transcriptional level, it directly suppresses eosinophil activation, degranulation, and chemotaxis, it reduces eosinophil survival signals and suppresses IL-4 and IL-13 (other Th2 cytokines). This leads to a 30-50% eosinophil count reduction, 20-40% IgE reduction, 40-60% IL-5 reduction, and effects are measurable within 4-6 weeks (faster than omega-3 alone)
Omega-3s shift the immune response away from Th2 dominance. High dose DHA decreases IgE and Th2 cytokines (IL-5, IL-13) and reduces eosinophil count reduction by 30-50%, improves barrier function by 20-30% and reduces itch intensity and flare frequency.
Vitamin D directly regulates immune function and supports barrier protein production. It directly suppresses Th2 immune responses and IL-5 production (the cytokine creating eosinophils). Vitamin D receptors on eosinophils signal reduced activity and D is essential for barrier protein production and infection resistance. By addressing the inflammatory driver that is actively damaging the barrier from within, eosinophils are reduced.
A zinc deficiency associated with elevated eosinophils and Th2 dominance. Supplementation helps normalize eosinophil counts.
Zinc is essential for immune regulation (shifts away from Th2 responses), critical for barrier integrity and protein synthesis, and
required for wound healing.
L-histidine is an essential building block for filaggrin synthesis (key barrier protein - Th2 cytokines actively suppress filaggrin production). Histidine is 48% of Natural Moisturizing Factor (NMF) in stratum corneum. It converts to urocanic acid (UV absorber, immunomodulator) and normalizes skin pH (alkaline pH worsens eosinophilic inflammation).
How they can work together:
Triple eosinophil suppression: Perilla (IL-5 inhibition) + DHA (pro-resolving mediators) + Vitamin D (Th2 modulation)
Dual barrier support: L-Histidine (filaggrin substrate) + DHA (lipid matrix) + Zinc (protein synthesis)
Mast cell-eosinophil axis disruption: Quercetin (stabilizes mast cells) + Perilla (prevents eosinophil response)
Immune rebalancing: Vitamin D + Zinc + DHA (shift from Th2 dominance)
With therapeutic supplementation, testing, correct dose and form is individual to each case and can be prescribed after a consultation. I work only with practitioner grade, high quality, excipient free supplements, free from unnecessary additives and many common allergens.
Especially for the treatment of AD, supplements must be free from wheat and gluten, soy, dairy, eggs, tree nuts, peanuts and sesame, artificial colours, flavours and sweetners, coatings and shellacs, GMOs, unnecessary binders fillers and preservatives, magnesium stearate, trans fat and hydrogenated oils.
Simultaneously with sufficient immune modulation the following needs to occur:
Environmental trigger removal - not as a general suggestion, but as a clinical priority. Your immune system is hyperreactive. Every DAMP and PAMP signal it receives keeps the alarm running. This is individual to each case.
Biofilm-aware infection management - understanding that recurring skin infections in this context require longer treatment windows and strategies that address bacterial colonisation at the source, including nasal carriage of Staphylococcus aureus.
Addressing the Cell Danger Response - supporting the body's ability to complete its healing sequence and move out of permanent defence mode.
This is not about abandoning medicine. It's about using a more complete picture of what's actually happening and working through it with a sequenced strategy.
The skin is where you see it. But the driver is systemic. And when you treat it that way, things can genuinely change.
Save this. Share it freely. This education if for everyone.
Lee.
