Infant Allergy Prevention & Eczema Mechanism Brief

Subject: ~5-month-old infant, exclusively breastfed, moderate-severe atopic dermatitis since ~6 weeks. Under combined paediatric dermatology + allergy specialist care. Currently on Eumovate (clobetasone butyrate 0.05%) bd → tapering; Epaderm ointment applied 30 min after; Cavilon No-Sting Barrier Film as drool/scratch barrier. Mother on dairy-free + gluten-free + soy-free diet — multi-allergen maternal exclusion in flight. Filaggrin flagged as likely driver. Both parents science-literate. Specialist follow-up imminent.

Purpose: Compress current best evidence into something parents can act on and use to interrogate the specialist. Compiled from primary literature via parallel research agents. This is a reference brief, not medical advice — every concrete action must be agreed with the treating clinician.

Current Specialist Regimen (confirmed in correspondence)

• Eumovate (clobetasone butyrate 0.05%) — moderate-potency topical steroid. Sits between hydrocortisone 1% (mild) and betamethasone valerate 0.1% (potent). Bd until itch-free → 2 further days → od → minimise to residual rough areas. Be more generous on troublesome areas (back, nappy area). UK potency context: clobetasone butyrate is a useful step up from hydrocortisone for moderate paediatric eczema while still considered safe for short courses on the face.
• Application sequence: Eumovate first, wait ~30 min for absorption, then Epaderm Ointment on top.
• Scalp: Eumovate to affected areas only (NOT whole scalp). Epaderm in addition only if scalp very dry.
• Skin barrier (drool/scratch): Cavilon No-Sting Barrier Film (3M) preferred; Vaseline acceptable alternative.
• Nappy area: emollient only; no proprietary nappy creams; no steroid; more nappy-free time.
• Maternal exclusion already in flight: dairy + gluten + soy-free. This is effectively the iMAP maternal CMPA trial plus extension — the questions now are (i) is this still needed at all and (ii) how to sequence reintroduction.
• Skin-prick testing deferred at the initial consult because eczema was too extensive. Reassessable at follow-up once skin is sufficiently clear — this is the biggest practical lever for the weaning conversation below.

TL;DR

1. The weaning window is open and time-sensitive. This infant is the textbook LEAP-eligible patient (severe early-onset eczema → high-risk tier per NIAID 2017 / BSACI 2018). Default (“wait and see”) = ~17–20% chance of peanut allergy by age 5. Early introduction collapses that to ~3%. NNT ≈ 7 (skin-prick negative cohort) or ≈ 4 (already sensitised). [Du Toit, NEJM 2015]
2. Eczema control is part of the allergy-prevention intervention, not separate from it. Inflamed/leaky skin is the sensitisation route (dual-allergen hypothesis); active eczema while introducing peanut and egg is the worst combination. Get skin near-clear before first dose — this is the PETIT lesson. The Eumovate proactive plan is doing exactly this.
3. Plan to the follow-up appointment:
   • Now → follow-up: Continue the Eumovate taper. Track itch-free / clear status site-by-site. Photograph skin daily. Hold off any new allergen introductions until the specialist re-examines skin and decides on SPT.
   • At follow-up: Push for the skin-prick test now skin is more controlled. Highest-value panel: peanut, egg, cow’s milk, sesame, tree nuts, wheat, soy. Also: weight check, vaccination-site reaction debrief, maternal reintroduction sequence.
   • Post-follow-up (assuming green light): First peanut dose using LEAP protocol — 2 g peanut protein × 3 days/week ≈ 6 g/week (smooth peanut butter thinned with breast milk; or Bamba softened). Sustain ≥5 years. Then well-cooked egg per PETIT. Then milk (yoghurt), wheat, sesame, tree nuts (smooth butters), fish, soy. One at a time, 2–3 day gap, daytime, cetirizine in the house.
4. Filaggrin status doesn’t change the management plan at this stage, but it raises the urgency of points 1–3 and justifies lifelong skin-care discipline. NHS doesn’t routinely genotype; private panel £150–400 if you want it (consumer DNA tests miss the most common European variant — false reassurance).
5. The CMPA trial is effectively already running on the mother’s side (dairy + gluten + soy-free maternal diet). The unanswered question is no longer “should we try elimination” but “what’s the structured reintroduction order and timing, and is iMAP Milk Ladder appropriate when reintroducing dairy?”
6. Stop wasting money on emollient bath additives (Oilatum/Aveeno bath oils) — BATHE trial, BMJ 2018, no benefit. Soap substitutes are fine; bath additives are not.

Part 1 — Mechanism: Filaggrin, Barrier, and the Atopic March

1.1 What filaggrin does

The FLG gene sits on chromosome 1q21.3 in the epidermal differentiation complex. It encodes profilaggrin, a ~400 kDa polyprotein stored in keratohyalin granules of the granular layer (Brown & McLean, J Invest Dermatol 2012). During terminal keratinocyte differentiation, profilaggrin is proteolytically processed into ~37 kDa filaggrin monomers, which aggregate keratin filaments — collapsing the corneocyte into the flat “brick” of the stratum corneum.

In the upper stratum corneum, caspase-14 further degrades filaggrin into free hygroscopic amino acids — pyrrolidone carboxylic acid (PCA), urocanic acid (UCA), histidine derivatives — collectively Natural Moisturising Factor (NMF) (Hoste et al., J Invest Dermatol 2011). NMF holds water, and via trans-UCA, acidifies the stratum corneum to pH ~5. That acidity:

• maintains lipid lamellae organisation (β-glucocerebrosidase activity is pH-dependent),
• restrains serine proteases (KLK5/7) that would otherwise digest desmosomes prematurely,
• suppresses Staphylococcus aureus growth (relevant — S. aureus drives infected eczema).

1.2 Loss-of-function variants

Four common European LoF alleles account for most carriers: R501X, 2282del4, R2447X, S3247X (Sandilands et al., Nat Genet 2007). Combined carrier frequency in Northern European populations is ~9–10%.

Effect sizes for atopic dermatitis (Palmer et al., Nat Genet 2006):

• Heterozygotes: OR ~3.1 (95% CI 2.4–4.0)
• Homozygotes/compound heterozygotes: OR ~7.7 (5.3–10.9)

FLG LoF also independently raises risk for peanut allergy (OR ~3–5) even adjusted for eczema severity (Brown et al., JACI 2011), and increases risk of eczema herpeticum and S. aureus colonisation.

Clinical bedside tells worth checking on the infant and both parents:

• Palmar hyperlinearity — accentuated palm creases. Most sensitive clinical sign.
• Keratosis pilaris — “chicken skin” on upper arms / outer thighs / cheeks.
• Ichthyosis vulgaris — fine scaling, especially on shins. Semi-dominant FLG phenotype.
• Early-onset (<1y), persistent eczema.

1.3 The barrier → atopic march pathway

The model (Irvine, McLean & Leung, NEJM 2011 — the definitive clinical review):

1. Reduced filaggrin → less NMF → higher SC pH, lower hydration, raised transepidermal water loss (TEWL).
2. Higher pH disinhibits KLK5/7 serine proteases, which cleave desmosomes (scaling) and activate PAR-2 on keratinocytes.
3. Damaged keratinocytes release epithelial alarmins — TSLP, IL-33, IL-25 — which prime dendritic cells and ILC2s toward a Th2 programme (IL-4, IL-5, IL-13). IL-4/IL-13 then further suppress filaggrin, loricrin, and involucrin — a feed-forward loop. This is why FLG-wildtype eczema also shows reduced filaggrin protein.
4. Percutaneous sensitisation: allergens (peanut, egg, HDM) penetrate the defective barrier into a Th2-skewed milieu. Without prior oral tolerance, this drives IgE class-switching → food allergy → asthma → rhinitis (“atopic march”).

1.4 Dual-allergen exposure hypothesis (Lack 2008)

Gideon Lack’s hypothesis: route of exposure determines fate.

• Oral exposure in early life → tolerance (via CD103⁺ gut DCs, Foxp3⁺ regulatory T-cells, TGF-β, IL-10 in gut-associated lymphoid tissue). Pabst & Mowat, Mucosal Immunol 2012.
• Cutaneous exposure through disrupted skin → Th2 sensitisation and IgE (via Langerhans cells, inflammatory dendritic epidermal cells, alarmin-conditioned DCs in skin-draining lymph nodes). Strid et al., Clin Exp Allergy 2005; Tordesillas et al., J Clin Invest 2014.

Direct evidence the route matters:

• Du Toit 2008 (JACI): UK Jewish children (delayed peanut intro) had 10× higher peanut allergy than Israeli Jewish children (Bamba peanut snack from ~7m) — same genetics, different exposure regime.
• Brough et al. (JACI 2014, 2015): household peanut consumption → peanut protein in house dust. In infants with filaggrin mutation or atopic dermatitis, every 3-fold increase in dust peanut → ~3-fold increased peanut sensitisation/allergy. Effect absent in barrier-intact children. Direct demonstration that the cutaneous route does the damage.
• HealthNuts cohort (Martin et al., Clin Exp Allergy 2015): infants with eczema had ~6× egg allergy risk and ~11× peanut allergy risk by 12m; early-onset eczema needing topical steroids → ~50% food-allergy prevalence.

Practical reading: Allergen on a parent’s/sibling’s hands transferring to an infant’s eczematous skin is a biologically real (not paranoid) sensitisation route. Wash hands before face/skin contact during high-allergen meals. But this is mitigation, not the main lever — the main lever is early oral introduction.

1.5 The cruel feedback

Eczema → barrier disruption → percutaneous sensitisation → systemic IgE → food allergen contact triggers further inflammation → worse eczema. This is why getting on top of the skin and inducing oral tolerance simultaneously is the dominant strategy, not sequentially.

Part 2 — Evidence Base: The Trials That Set the Protocol

2.1 Early oral introduction works (and the effect is huge)

LEAP — Du Toit et al., NEJM 2015;372:803–13. The trial that changed guidelines.

• 640 high-risk infants (severe eczema and/or egg allergy), aged 4–11 months.
• Randomised to peanut consumption (~6 g protein/week) vs strict avoidance to age 5.
• SPT-negative cohort: peanut allergy 1.9% (consumption) vs 13.7% (avoidance). 86% RRR (ITT).
• SPT-positive cohort (1–4mm wheal): 10.6% vs 35.3%. 70% RRR.
• NNT ≈ 7 (SPT-neg) or 4 (SPT-pos).

LEAP-On — Du Toit, NEJM 2016;374:1435–43. 12 months of peanut avoidance after age 5 did not reverse tolerance. Sustained, not lifelong, intake is what matters.

LEAP-Trio — NEJM Evidence 2024. Protection persists into adolescence (~71% RRR at 12+) despite ad-lib intake.

PETIT — Natsume et al., Lancet 2017;389:276–86. Japanese infants 4–5m with eczema; stepwise heated egg powder from 6m.

• Egg allergy at 12m: 8% (egg) vs 38% (placebo). 78% RRR. NNT ≈ 3. Stopped early for efficacy.
• Critically: eczema was aggressively treated in both arms. Early egg + skin optimisation = combined intervention.

EAT — Perkin et al., NEJM 2016;374:1733–43. General UK population; 6 allergens from 3m vs EBF to 6m.

• ITT: 5.6% vs 7.1% any food allergy (NS — adherence was poor, only 42% hit target intake).
• Per-protocol significant: peanut 0% vs 2.5%; egg 1.4% vs 5.5% (75% RRR).
• Reads as: works if you actually do it; 3m start is feasible but hard while EBF.

PreventADALL — Skjerven et al., Lancet 2022;399:2398–2411. General population, factorial trial.

• Food intervention (peanut, milk, wheat, egg tastes from 3m): food allergy at 36m 0.5% vs 2.0% (OR 0.24). Peanut specifically reduced.
• Skin emollient arm: no benefit for eczema or food allergy.

HEAP — Bellach et al., JACI 2017;139:1591–9. Pasteurised egg-white powder from 4–6m in unselected German population → no prevention benefit AND a safety signal (10/23 already-sensitised babies anaphylaxed on first dose).

• Lesson: never introduce raw / lightly-cooked egg in unscreened high-risk infants. Well-cooked egg only at home.

2.2 Prophylactic emollients don’t prevent eczema

BEEP — Chalmers et al., Lancet 2020;395:962–72. 1,394 high-risk neonates, daily emollient from birth.

• Eczema at 2y: 23% (emollient) vs 25% (control). aRR 0.95. Null.
• Skin infections HIGHER in the emollient arm. Food allergy: non-significant upward signal.
• 5-year follow-up confirmed no benefit.

PreventADALL skin arm (Skjerven 2020) — bathing + facial emollient from 2 weeks → no eczema prevention.

STOP-AD (Ní Chaoimh et al., BJD 2023) — twice-daily emollient → reduced eczema at 12m in 321 infants, but effect waned and trial was smaller. Outlier.

Cochrane 2021 (Kelleher et al.) + EAACI 2023 guideline: emollients should not be recommended for primary prevention. Treatment indication for established eczema is unchanged and strong.

2.3 Proactive corticosteroids beat reactive

Schmitt et al., BJD 2011 — meta-analysis 8 RCTs n=1,247: proactive TCS (2x/week to recurrence-prone sites after clearing flare) reduced relapse risk ~60% (OR 0.46). AAD 2023 guideline (Sidbury et al., JAAD 2023) endorses.

Steroid phobia is unfounded for mild TCS in infants. Atrophy from hydrocortisone 1% used appropriately is essentially unreported (Mooney et al., BJD 2015; NEA 2018 position).

2.4 Other interventions worth knowing

• Topical calcineurin inhibitors (tacrolimus 0.03%, pimecrolimus 1%): off-label <2y but widely used; PETITE trial n=2,418 infants 3–12m, 5y follow-up — confirmed safety (Sigurgeirsson et al., Pediatrics 2015). FDA black-box warning now considered unsupported (Paller et al., APPLES study, JAAD 2020).
• Crisaborole 2% (PDE4 inhibitor): licensed from 3m. CrisADe CARE 1 evidence base.
• Bathing additives (Oilatum, Balneum, Aveeno bath oil): BATHE trial, BMJ 2018 — no clinically meaningful benefit. Stop using.
• Bleach baths: 0.005% sodium hypochlorite (~80 mL household 6% bleach in a full infant bath), 2x/week. Mixed evidence (Chopra 2017 meta-analysis), but a reasonable trial after recent S. aureus-positive flares.
• Wet wraps: short courses (24–48h) with diluted TCS for severe flares. ~10× TCS penetration. Watch for HPA-axis suppression with prolonged use.
• Water softeners: SOFTENED-Eczema trial, PLoS Med 2018 — null. Skip the plumbing.

Part 3 — Practical Protocol Template

Do not start point 3 (allergen introduction) before the dermatologist/allergist reviews.

3.1 Skin (weeks 0–2)

• Bath: daily, lukewarm, 5–10 min. Epaderm Ointment or Aveeno wash as soap substitute. No bath additive.
• Emollient: Epaderm Cream liberally within 3 minutes of bathing AND at every nappy change. Target 250–500g/week.
• TCS proactive plan:
  • Body: betamethasone valerate 0.1% short burst (7d bd) → taper to alternate days 1 week → 2 days/week maintenance.
  • Face: hydrocortisone 1% bd until clear → 2 days/week proactive maintenance. Face is safe with mild TCS in infants.
• Bleach bath: 2x/week for 4 weeks if recent S. aureus infection. Discuss with derm.
• Discuss with derm: tacrolimus 0.03% ointment or pimecrolimus for face as steroid-sparing if frequent face flares persist.

3.2 Environment

• Anti-allergen bedding covers, 60°C wash weekly.
• Humidity 40–50% (dehumidifier if needed).
• Hand hygiene before face/skin contact during high-allergen meals.

3.3 Allergen introduction (after derm/allergist sign-off)

Pre-introduction:

• Request peanut + egg sIgE (faster than SPT in UK). Interpretation:
  • sIgE <0.35 kU/L → low risk, home intro fine.
  • 0.35–5 kU/L → discuss with allergist; consider SPT and/or supervised first dose.

  • 5 kU/L or SPT ≥8 mm → likely sensitised; allergist-led plan.

• BSACI permits cautious home introduction without testing if eczema is well-controlled — testing should not delay introduction by more than 2–3 weeks.

Peanut — LEAP dose:

• Form: smooth peanut butter thinned with warm water / breast milk to runny paste, OR Bamba puffs softened (8 g Bamba ≈ 2 g peanut protein).
• Day 1: rub small amount on inside of lip, wait 10 min. If no reaction → ⅛ tsp (~0.5g peanut protein). Observe 2 hours.
• Build to 2 g peanut protein × 3 days/week = 6 g/week. Sustain to ≥5 years.
• Whole nuts: choking hazard. Never. Smooth nut butters only until age 5+.

Egg — PETIT dose:

• Well-cooked egg only — hard-boiled, or fully scrambled. Never raw/lightly cooked at home (HEAP signal).
• Start ¼ tsp mashed boiled egg, build to ~⅓ whole egg several times/week.

Then in order:

• Cow’s milk — easiest as yoghurt (no need to stop breastfeeding).
• Wheat — Weetabix, bread.
• Sesame — tahini smear.
• Tree nuts — smooth almond/cashew/walnut butters.
• Fish — well-cooked, low-mercury (cod, salmon).
• Soy — yoghurt or tofu.

Rules:

• One new allergen at a time.
• 2–3 day gap between new introductions.
• Daytime, ≥1 parent present.
• Cetirizine in the house (2.5mg from 6m — preferred over Piriton: less sedating, longer-acting).
• Once tolerated: keep in diet ≥2–3×/week. Re-exposure ≥weekly maintains tolerance.

Reaction recognition:

• Mild (perioral hives, single vomit, mild rash): oral cetirizine. Observe. Do not re-challenge same day.
• Anaphylaxis — any of: persistent cough/wheeze/stridor, swelling of tongue/throat, repeated vomiting + skin signs, floppiness, pallor + circulatory signs: 999, lie flat, legs up. Auto-injector if prescribed.

3.4 CMPA — when (and only when) to trial

Don’t trial elimination before optimised topical therapy. If eczema persists after 2–4 weeks of the regimen in 3.1, then:

• Maternal strict elimination 2–4 weeks: all dairy (milk, cheese, butter, yoghurt, whey, casein — lactose-free dairy still contains protein). Read labels for hidden casein/whey. Consider soy elimination (30–50% cross-reactivity per BSACI 2014).
• Maternal supplementation: calcium 1,000 mg/d + vitamin D 10 µg/d.
• Continue breastfeeding. Do not switch to hypoallergenic formula on speculation — UK overdiagnosis is severe (Munblit et al., JAMA Pediatr 2020).
• If symptoms resolve → maternal reintroduction → recurrence = diagnosis. Continue avoidance to 9–12 months, then re-challenge via iMAP Milk Ladder: baked milk biscuit → muffin → pancake → cheese → yoghurt → fresh milk (1–2 weeks per step).

3.5 Antihistamines: when (and when NOT)

Don’t use Piriton (chlorphenamine) or other sedating antihistamines:

• Sedating first-generation antihistamines are now considered suboptimal in infants. Paradoxical excitation common; rare but documented respiratory depression <2y; daytime drowsiness affecting feeding/alertness.
• Crosses blood–brain barrier; second-generation antihistamines don’t.
• BSACI / NICE / EAACI guidance has moved away from sedating antihistamines as first-line in young children.

Antihistamines don’t treat eczema itch:

• Eczema itch is non-histaminergic — driven by IL-31, TSLP, and direct neural sensitisation, not mast-cell histamine.
• Cochrane reviews (Apfelbacher 2013, van Zuuren 2017): oral antihistamines have no meaningful benefit on eczema itch.
• Any apparent “improvement” on sedating antihistamines is sedation, not itch relief.
• The topical corticosteroid regimen IS the itch treatment. Don’t chase the symptom — chase the substrate.

Cetirizine is the right antihistamine to have in the house — but ONLY for allergen-introduction reactions:

• Modern first-line non-sedating antihistamine for mild allergic reactions.
• Licensed from 6 months in the UK. If introduction starts before 6m, off-label use requires explicit specialist sanction.
• Standard dose ≥6m: 2.5 mg = 2.5 ml of 1 mg/ml syrup.
• Use case: mild reaction during allergen introduction (perioral hives, single vomit, mild rash). Observe; do not re-challenge same day.
• Do NOT pre-dose “just in case” before a first allergen feed — masks early warning signs. Treat actual reactions only.
• Do NOT substitute cetirizine for the anaphylaxis pathway. Antihistamines do not treat anaphylaxis; adrenaline does. 999, lie flat, legs up, auto-injector if prescribed.

Real itch-management toolkit (non-pharmacological):

• Proactive TCS plan (the substrate fix).
• ScratchSleeves / mittens at night.
• Cool room (~18°C) — overheating drives itch dramatically.
• Distraction during peak itch moments.

SPT washout rule: stop any antihistamine 5–7 days before any skin-prick test. Factor into scheduling.

Specific ask for the treating specialist: if the infant is <6m at first allergen introduction, get explicit sanction (and dose confirmation) for off-label cetirizine in the house ready for use.

Part 4 — Filaggrin Genotype Testing: Worth It?

NHS: not routinely commissioned. Tertiary centres occasionally (GOSH, St Thomas’, Dundee).

Private clinical: specialist allergy clinics offer 4–6 variant panels (R501X, 2282del4, R2447X, S3247X — captures >90% of European carriers). Cost £150–400.

Consumer (23andMe/Ancestry): avoid for this purpose. 23andMe has R501X on some chip versions but 2282del4 is an indel poorly captured by SNP chips — you’ll miss the most common European variant and get false reassurance. Promethease on raw data has the same limitation.

What it tells you that the phenotype doesn’t: little at age 5 months. The clinical picture (moderate-severe early-onset eczema + palmar hyperlinearity check + family history) already implies a barrier phenotype and dictates the same plan. A positive result reinforces discipline; a negative does not rule out a barrier defect — 60–70% of eczema is FLG-wildtype, and other barrier genes contribute (TMEM79/MATT, LOR, SPINK5, CLDN1, FLG2).

Verdict: academically interesting, not management-changing right now. If parents want it for future-proofing (planning whether siblings need the same vigilance, future occupational guidance — avoid wet work, irritant occupations), it’s defensible. Not urgent.

Part 5 — Allergy Testing: Blood (sIgE) vs Skin-Prick (SPT)

Both measure IgE sensitisation; both have a role. Important when SPT is deferred due to extensive eczema — blood testing does not require clear skin or antihistamine washout.

Specific IgE blood tests (sIgE)

• ImmunoCAP (Thermo Fisher / Phadia) = gold-standard assay; Immulite is the other major platform.
• Measures circulating IgE against specific allergens; reported in kU/L.
• Rough cut-offs: <0.35 negative · 0.35–0.7 low · 0.7–17.5 graded positive · >17.5 high.
• Available NHS via paediatric allergy clinic (slow), privately via specialist consult, or direct-to-consumer (Medichecks ~£100–250).
• Direct-to-consumer panels are a trap if they test IgG — IgG only means exposure, not allergy. Make sure any test is specifically sIgE / ImmunoCAP.

Component-Resolved Diagnostics (CRD) — the upgrade

CRD tests IgE against specific protein components rather than whole allergen extracts. This distinguishes “you’ll anaphylax to peanut” from “you’ll get a tingly mouth from raw apple.”

• Peanut: Ara h 2 is the key marker. Ara h 2 ≥0.35 kU/L has high positive predictive value for true clinical peanut allergy. Ara h 1, 3, 6 = also storage proteins, similar significance. Ara h 8 = PR-10, usually cross-reactive with birch pollen → oral allergy syndrome only, mild.
• Egg: ovomucoid (Gal d 1) = heat-stable. Predicts whether baked egg will be tolerated. Negative ovomucoid + positive whole egg = likely baked-egg-tolerant.
• Milk: casein (Bos d 8) = heat-stable. Predicts baked-milk tolerance.

SPT vs sIgE — when to use which

Best practice: triangulate. SPT + sIgE + clinical history together is more informative than any one alone.

Highest-value asks if running bloods

• Ara h 2 (peanut storage protein)
• Gal d 1 (ovomucoid) + whole egg sIgE
• Whole cow’s milk sIgE + Bos d 8 (casein)
• Sesame, hazelnut/cashew/walnut, wheat, soy
• Optional: dust mite (Der p 1, Der p 2), grass, mould — relevant if environmental triggers are suspected.

GP can request via NHS but turnaround is slow and component testing isn’t always available. Faster route: ask the treating specialist to order ahead of the next consult so results are in hand at the appointment.

Part 6 — Peanut + Egg Introduction: Practical Detail

PEANUT — LEAP protocol

Target dose: 2 g peanut protein × 3 days/week ≈ 6 g/week, sustained to ≥5 years.

This is the exact LEAP-tested dose. Lower may work (PreventADALL got benefit at smaller “tastes”) but 6 g/week is the only number with definitive RCT evidence.

What 2 g of peanut protein looks like:

• Smooth peanut butter (~25% protein): ~8 g ≈ 1.5–2 level teaspoons.
• Bamba puffs (~25% peanut protein content): one ~28 g bag ≈ ~7 g peanut protein → ~⅓ bag per feed = 2 g. Bamba is engineered for this: easy dose, melts in mouth, low choking risk.
• Peanut powder (e.g. PB2, ~50% protein): ~4 g powder = 2 g protein.
• Whole peanuts: NEVER until age 5+. Choking hazard.

First dose protocol (daytime, both parents around, cetirizine + 999 ready):

1. Lip-rub test. Smear tiny amount inside lower lip. Wait 10 min. Watch for redness, swelling, hives, vomit, distress.
2. If clear → first dose: ~⅛ tsp smooth peanut butter, thinned with warm water or breast milk to runny paste. Spoon-feed.
3. Observe 2 hours. Most IgE reactions <30 min; rare delayed up to 2 h.
4. If clear, stop for the day.
5. Days 2–3: repeat at the same dose, then build over 1–2 weeks toward 2 g protein × 3×/week.

Cadence: Three feeds per week is the LEAP-tested minimum. Some clinicians advise daily for simplicity. Once tolerance is established, the lower bound for maintenance appears to be approximately weekly — stick close to 3×/week to be safe.

Reaction recognition:

• Mild (perioral hives, single vomit, mild rash): oral cetirizine (2.5 mg from 6m — preferred over Piriton: less sedating, longer-acting). Observe. Do not re-challenge same day.
• Anaphylaxis — 999, lie flat, legs up: persistent cough/wheeze/stridor, tongue/throat swelling, repeated vomiting + skin signs, floppiness, pallor + circulatory collapse.

EGG — PETIT protocol

Critical safety rule: WELL-COOKED EGG ONLY at home. Hard-boiled, fully scrambled (no runny bits), or baked into cake/muffin. Never raw, lightly cooked, soft-boiled, runny-yolk, or in mousses/mayonnaise/hollandaise.

HEAP used pasteurised raw-equivalent egg powder and got ~30% anaphylaxis rate on first dose. PETIT used heated egg and got NNT 3 with no serious safety signal. Heat denatures most egg-white allergens. Ovomucoid (Gal d 1) survives — which is why baked-egg tolerance doesn’t always equal raw-egg tolerance.

PETIT trial dose:

• Months 6–9: 50 mg heated egg powder/day (≈ 0.2 g cooked egg)
• Months 9–12: 250 mg/day (≈ 1 g cooked egg)

In practice this is “start with a smear” — exposure, not nutrition.

Practical home version:

1. First dose: ¼ tsp mashed hard-boiled yolk, mixed with breast milk. Lip-rub → small spoon → observe 2 h, same as peanut.
2. Yolk first, then white. Yolk is less allergenic. Some clinicians introduce yolk for a week before adding white; others use whole hard-boiled egg from the start. Confirm with treating specialist.
3. Build over 2–3 weeks toward roughly ⅓ of a hard-boiled egg several times per week, sustained.
4. Baked egg is the easiest format for daily intake — small piece of cake/muffin/pancake made with whole egg, baked at >170°C for >20 min. Tolerating baked but not lightly-cooked = baked-egg-tolerant, a real intermediate state most kids outgrow within a couple of years.

Universal rules (peanut and egg)

• One new allergen at a time.
• 2–3 day gap between different allergens (to identify which caused any reaction).
• Daytime, ≥1 parent present.
• Cetirizine in the house. Baby’s weight written down for paramedics.
• Once tolerated, KEEP IT IN THE DIET — minimum 2–3×/week. The biggest mistake in this protocol is introducing successfully then drifting away. Kids can lose tolerance with prolonged avoidance.
• Length of commitment: ≥5 years for peanut (LEAP-On showed 12 mo avoidance at age 5 didn’t reverse tolerance — but trial was at age 5, not earlier). Egg: similar logic, less hard data — assume ≥2–3 years of regular exposure minimum.

Cheat sheets

• Peanut weekly target: 6 g protein. Achievable as ~24 g smooth peanut butter across 3 feeds (≈4 tsp/week, ≈1.5 tsp per feed), or ~1 small bag of Bamba per week across 3 sittings.
• Egg weekly target: roughly 1 hard-boiled egg’s worth across 3+ feeds, all well-cooked. Easier to deliver via baked goods than via plain egg.

Part 7 — Order of Introduction: Why Peanut First

Default: peanut first, then egg ~1–2 weeks later. It’s a default not a dogma — peanut + egg in tandem is also defensible.

Why peanut first

1. Strongest evidence. LEAP → LEAP-On → LEAP-Trio is the most robust early-introduction dataset for any single allergen. ~86% RRR, sustained into adolescence.
2. Highest stakes. Peanut allergy is the most likely to cause anaphylaxis and the least likely to be outgrown — only ~20% outgrow it (vs ~70% for egg, ~80% for cow’s milk). Biggest lifetime payoff.
3. Cleanest delivery. Smooth peanut butter / Bamba dose easily. Egg requires the well-cooked-only rule + yolk-vs-white sequencing. Milk via yoghurt is easy but lower-impact (most outgrow CMPA anyway).
4. Single hit, big effect. Get peanut in and sustained → moved the needle on the single most consequential food allergy.

Why “one at a time” is a safety protocol, not a biological necessity

• PreventADALL introduced four allergens simultaneously (peanut, milk, wheat, egg) from 3 months → significant food-allergy reduction.
• EAT introduced six simultaneously at 3 m.
• Peanut + egg in parallel (1–2 week stagger) is defensible; some allergists prefer it because egg’s PETIT-style ramp takes weeks anyway.
• The reason to space them is so you can identify which allergen caused any reaction — not because the immune system needs them sequenced.

The exception that flips the order

• If sIgE / SPT shows the infant is already sensitised to peanut (e.g. Ara h 2 ≥0.35 kU/L, or SPT wheal ≥8 mm), peanut introduction moves to a hospital/supervised setting.
• In that case, start with egg at home in the meantime.
• This is why getting bloods done before the next clinic visit is valuable — tells you which lane you’re in before deciding what to introduce first.

Bottom line

• Default plan: peanut first, then egg ~1–2 weeks later once peanut is established.
• If SPT/sIgE shows peanut high → supervised peanut, egg first at home.
• If both low → start peanut at home that week.
• Specific question for the specialist: staggered or peanut + egg in tandem? UK paediatric allergists vary on this.

Part 8 — Questions for the Treating Specialist

1. Skin-prick testing today. Is the skin sufficiently settled to perform SPT in this consult? Priority allergens: peanut, egg, cow’s milk, sesame, tree nuts (mixed), wheat, soy, dust mite, mould, grass.
2. Weaning roadmap. What’s the recommended introduction order and dosing? Specifically: (a) endorse the LEAP 6g peanut protein/week target, (b) PETIT-style well-cooked egg, (c) which to introduce first if SPT defers some?
3. First-dose setting. Home OK, or supervised first dose for the high-risk allergens given eczema history?
4. Maternal reintroduction sequence. What pace, in what order — and does iMAP Milk Ladder apply for dairy? Should soy/gluten be brought back first since CMPA is the higher-prior suspicion?
5. Filaggrin. Does the clinic offer genotyping? Worth it for this patient or for sibling/parent counselling? Any clinical tells in the family worth checking (palmar hyperlinearity, keratosis pilaris, ichthyosis vulgaris)?
6. Tacrolimus / pimecrolimus / crisaborole as steroid-sparing options for face once Eumovate taper completes — preferred agent, threshold to introduce?
7. Persistent flare zones. Anything beyond more generous Eumovate + barrier? Bleach bath protocol given recent S. aureus infection?
8. Vaccination-site reactions. Pre-medicate next round? Schedule SPT well clear of next vaccination date?
9. Weight plateau. If growth doesn’t pick up with weaning progression, paediatric referral threshold?
10. Eczema herpeticum red flags. Clustered punched-out vesicles, fever, lethargy — emergency pathway?
11. Long-term trajectory. For moderate-severe early-onset eczema with optimised early treatment + early allergen introduction, what’s the literature on resolution by 5y and atopic march to asthma/rhinitis?

Part 9 — Key References

Filaggrin & barrier:

• Palmer CN et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006;38:441–446.
• Sandilands A et al. Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 2007;39:650–654.
• Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. NEJM 2011;365:1315–1327. [DEFINITIVE CLINICAL REVIEW]
• Brown SJ, McLean WH. One remarkable molecule: filaggrin. J Invest Dermatol 2012;132:751–762.
• Hoste E et al. Caspase-14 is required for filaggrin degradation to natural moisturising factors. J Invest Dermatol 2011;131:2233–2241.

Dual-allergen exposure:

• Lack G. Epidemiologic risks for food allergy. JACI 2008;121:1331–1336.
• Du Toit G et al. Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. JACI 2008;122:984–991.
• Tordesillas L, Berin MC. Mechanisms of oral tolerance. Clin Rev Allergy Immunol 2018;55:107–117.
• Strid J et al. Disruption of the stratum corneum allows potent epicutaneous immunisation with protein antigens. Clin Exp Allergy 2005;35:757–766.
• Tordesillas L et al. Skin exposure promotes a Th2-dependent sensitisation to peanut allergens. J Clin Invest 2014;124:4965–4975.
• Brough HA et al. Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitisation and likely peanut allergy. JACI 2014;134:867–875.

Early introduction RCTs:

• Du Toit G et al. Randomised trial of peanut consumption in infants at risk for peanut allergy (LEAP). NEJM 2015;372:803–813.
• Du Toit G et al. Effect of avoidance on peanut allergy after early peanut consumption (LEAP-On). NEJM 2016;374:1435–1443.
• Natsume O et al. Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT). Lancet 2017;389:276–286.
• Perkin MR et al. Randomised trial of introduction of allergenic foods in breast-fed infants (EAT). NEJM 2016;374:1733–1743.
• Skjerven HO et al. Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL). Lancet 2022;399:2398–2411.
• Bellach J et al. Randomised placebo-controlled trial of hen’s egg consumption for primary prevention in infants (HEAP). JACI 2017;139:1591–1599.

Prophylactic emollients:

• Chalmers JR et al. Daily emollient during infancy for prevention of eczema (BEEP). Lancet 2020;395:962–972.
• Skjerven HO et al. Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL skin arm). Lancet 2020;395:951–961.
• Kelleher MM et al. Skin care interventions in infants for preventing eczema and food allergy. Cochrane Database 2021.

Eczema management:

• Schmitt J et al. Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema. BJD 2011;164:415–428.
• Santer M et al. Emollient bath additives for the treatment of childhood eczema (BATHE). BMJ 2018;361:k1332.
• Sidbury R et al. American Academy of Dermatology guidelines of care for the management of atopic dermatitis. JAAD 2023;89:e1–e20.
• Sigurgeirsson B et al. Safety and efficacy of pimecrolimus in 5-year follow-up of infants with atopic dermatitis (PETITE). Pediatrics 2015;135:597–606.
• Chopra R et al. Efficacy of bleach baths in reducing severity of atopic dermatitis: a systematic review. Ann Allergy Asthma Immunol 2017;119:435–440.

CMPA:

• Luyt D et al. BSACI guideline for the diagnosis and management of cow’s milk allergy. Clin Exp Allergy 2014;44:642–672.
• Venter C et al. Better recognition, diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy: iMAP. Clin Transl Allergy 2017;7:26.
• Munblit D et al. Assessment of evidence about common infant symptoms and cow’s milk allergy. JAMA Pediatr 2020;174:599–608.

Guidelines:

• Togias A et al. NIAID-sponsored addendum guidelines for prevention of peanut allergy in the United States. JACI 2017;139:29–44.
• Turner PJ et al. Implementing primary prevention of food allergy in infants (BSACI position statement). Clin Exp Allergy 2018;48:912–915.
• Santos AF et al. EAACI guidelines on the diagnosis of IgE-mediated food allergy. 2024.
• NICE NG134 (food allergy in under-19s), NICE CG57 (atopic eczema in under-12s, reviewed 2023).

Brief compiled from parallel literature review (four research agents). Sources prioritised: PubMed-indexed RCTs, Cochrane reviews, BSACI/NIAID/EAACI guideline documents. Author has no medical training; this brief is for parental education and specialist consultation, not as standalone medical guidance.