Age of onset and severity of eczemaEczema Miyaji ¥ et al. duration associated with food allergy 100% FA() 80% MFA (+) 60% , & 40% = wll » | H 1 3 4 5 6 7 8 9 10 11 (aonths) (n=) 8) 2H) 3) 83) 2) GH UDG) (6) Time until the start of aggressive treatment Earlier aggressive treatment to shorten the duration of eczema in infants resulted in fewer food allergies at 2 years of age. JACI IP 2020;8(5):1721-1724MMU eM ee ta Ce ee eke ere ue) Viruses * Detergents * facta Le Oo a® s Peanuts d ceo | ign pH reams a Genet factors FG LOR z SIX as 4, Nadeau KC, Sindher SB, ered hep Chan S, Bahnson H, Leung DYM, Lack G. Epicutaneous sei Wlerqy: whi vidence and how can thi: revented? Allergy. 2020 Apr1) Skin barrier impairment due to environmental : pollutants, detergents, 4 infections, and genetics 2 Skin barrier impairment leads to skin inflammation and clinical AD ‘ FLG oss-o-funetion Fung) 3) Exposure to food allergens through skin that has an impaired barrier (dry) or clinical AD leading to sensitization and FA kG. 2 ‘Nadeau KC, Sindher SB, Alkotob SS, CI ent of food alleray: what is the ¢ Allergy. 2020 Apr 6.Atergane Enveonmeniat sere Saurus FG =. Ts Lay ew | «=~ @- ” Y re ie ‘specte e eau KG, Sindher SB, Alkotob $5, Chan S, Bahnson H, Leung DYM, Lack G. Sd? Allergy. 2020 Apr 6.AD at 6 months Pilot preventative emollient therapy — AD reduction US/UK BEEP pilot study Japanese study +e we 41% 50% ; ee 50% ee 40% 5 40% g 32% . 30% 30% 22% S 20% 2 20% 10% 10% % 0% Emolient therapy (n=55) Control (n=59) Emollient therapy (n=$3) Control (n=59) UK: Doublebase gel, sunflower seed oil, WSP. Douhet (shiseido) cream US: Aquaphor healing ointment, Cetaphil cream ‘Simpson EL et al. J Allergy Clin Immunol. 2014;134:818-823. Horimukai K et al. J Allergy Clin Immunol. 2014;134:824-830 e826.Barrier enhancement eczema prevention (BEEP) * 1395 infants with family history of atopy * Doublebase gel and /or Dibrobase cream * From <3 weeks-12 months 3-4 times a week (51% adherence) * Did not prevent, delay or reduce severity of AD * Increased skin infections (0.23/yr vs 0.15/yr) * Trend to towards increase in food allergy Chalmers JR et al, Lancet. 2020;395(10228):962-972.Barrier enhancement eczema prevention (BEEP) ee neg. Preventative emollient smt'Control arm ap es R Sa a xx aq adjusted RR aq 1-47, 95% Cl 0-93-2-33 x eo PRIMARY PARENTAL PARENTAL SPT>/=3MM FA (MILK, EGG, OUTCOME UKWP REPORT UKWP REPORTUKWP = (MILK,EGG, PEANUT) AT 2 ADAT2YEARS AT 1 YEAR AT 2 YEARS — PEANUT) AT 2 YEARS YEARS Chalmers JR et al. Lancet. 2020;395(10228):962-972.PreventADALL study. NHN: * n=2701, general population, 4 arm study * Paraffin based bath oil additive i * Alcohol/ paraffin-based face cream (Ceridal) * 2 week-9 months 4 days per week (27% adherence) * Peanut, milk, wheat, egg ‘tasters’ from 3m * No difference in skin infections Skjerven HO et al. Lancet.2020;395(10228):951-961.PreventADALL results | Intervention decreases incidence _Intervention increases incidence Earlier onset of AD in ve emollient arm ‘Atopic dermatitis skin intervention) | i p-0074 Atopicdermatt (fod interven > | topic dermatitis (food intervention) moe | pAD (skin intervention) 056 . fe No interaction AD (oodinervention) <5 with parental i atopy a } 3 a 5 Risk diference() Figure 2: Risk reduction of atopic dermatitis fr each primary prevention strategy pAD=possble atopic dermatitis, Skjerven HO et al. Lancet.2020;395(10228):951-96125% © Se 20% Be 22 15% Sa Pa 10% bs 7 5% 0% | m Control (n=36) Epiceram ITT (n=34) 1 Epiceram PP (n=21) ITT: Visible AD at 12m 16% vs. 5% (p=0.15) Milk 5.6% 2.9% 0.0% Eee 16.7% 5.9% 0.0% | Peanut Any food 8.3% 19.4% 2.9% 8.8% 0.0% 0.0% Lowe AJ et al. Br J Derm 2018; 178:e1-e21Preventive emollient therapy * Petrolatum based emollients: * No effect for AD prevention, severity, time of onset * Increase in skin infections (BEEP) * Trend towards sensitisation and food allergy (BEEP) * Trlipid based emollients: * Positive results on pilot study for AD and SPT * PEBBLES RCT (NCT 03667651) 760 high-risk infants (Aus)TEWL after petrolatum vs trilipids for 5 weeks ™ +4 \ n=4§ children with dry skin/AD 2s- a aw, "71 — 3m —7 years “yo - Lvs. Rarm 1o-, i Daily application | Blinded Bascline After aveena for § weeks Baseline Aller epiceram for $ weeks Sindher T et al. Pilot Study Measuring TEWL in Children Suggests Trilipid Cream Is More Effective Than a Paraffin-Based Emollient. 2020 Allergy\gG4/IgE in infants with AD/dry skin: Aveeno vs trilipid corm e "| 2500000; osm rou * < o | 2000000: 2 = ©: ° ° 2 is § sso0000- | e : : 2 3 : 3 to00000 Bases : 5 . FTW] © 500000 op ee += -4— — ay o| —e 2 = j Baseline Week 12 Baseline Week 12 Baseline Week 12 Baseline Week 12 ‘Aveeno Epiceram Aveeno Epiceram Study time © Baseine © Week'2 Study time @ Baseline © Week12 Sindher T et al. Increases in plasma IgG4/IgE with trilipid vs paraffin/petrolatum-based emollients for dry skin/eczema 2020 PALS. aureus and Food Allergy in éarly childhood Enhanced IgE Production Inhibition of Oral Tolerance to Peanut, Delay in Resolution of Egg Allergy + association is inclependlent of eczema severity christou O et al, JACI 2019: 144(2}: 494-503Immune Barrier Response Leung DYM et al. Deciphering the Complexities of Atopic Dermatitis: Shifting Paradigms in Treatment Approaches JACI 2014;134:769-79.Early proactive topical steroids associated with reduced FA . 45% reduction in food allergy by 2 yrs 60% reduction in egg allergy (egg, milk, wheat, soy, peanut, fish) in egg sensitized patients aaa ‘yoo ran ‘p=0003 arAL BRAG wr rae AAG yn) CO} 7 ee recommended (reatient (n2128) Miyaji ¥ et al. Earlier aggressive treatment to shorten the duration of eczema in infants resulted in fewer food allergies at 2 years of age. J Allergy Clin Immunol Pract. in press.Secondary prevention study in AD infants + Multicenter, investigator-blinded, RCTI (PACI Study, Japan, n=650) * Twice daily emollient therapy from 7-13 weeks * Heparinoid cream (Hirudoid® Soft ointment) twice daily * Proactive steroid treatment from 7-13 weeks (BD for 2/52 then twice weekly BD) * Face: Alclometasone dipropionate (low potency) * Body: Betamethasone valerate (intermediate potency) * OFC proven IgE mediated egg allergy at 6 months UMINO00028043 doi.org/10.1186/s13601-018-0233-8_ a LE Future research perspectives * Optimum initiation and duration of intervention * Degree of adherence * Different emollient properties * Role of environmental food exposure * Role of staphylococcus aureus * Primary or secondary prevention * Role of topical anti-inflammatory agents