Restricted accessResearch articleFirst published online 2019-11
Approach to the Assessment and Management of Pediatric Patients With Atopic Dermatitis: A Consensus Document. Section III: Treatment Options for Pediatric Atopic Dermatitis
Because atopic dermatitis (AD) is a chronic, relapsing disease, treatment requires the use of both active therapy to control flares and preventative maintenance therapy to promote integrity of the skin barrier. In this third of four sections, important clinical considerations for the treatment of pediatric AD are reviewed. Emerging therapies in development for pediatric AD are introduced.
SidburyR.DavisDM.CohenDEet al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71(2):327-349.doi:10.1016/j.jaad.2014.03.030
Angelova-FischerI.NeufangG.JungK.FischerTW.ZillikensD. A randomized, investigator-blinded efficacy assessment study of stand-alone emollient use in mild to moderately severe atopic dermatitis flares. J Eur Acad Dermatol Venereol. 2014;28(Suppl 3):9-15.doi:10.1111/jdv.12479
4.
HorimukaiK.MoritaK.NaritaMet al. Application of moisturizer to neonates prevents development of atopic dermatitis. J Allergy Clin Immunol. 2014;134(4):824-830.doi:10.1016/j.jaci.2014.07.060
5.
XuS.ImmaneniS.HazenGB.SilverbergJI.PallerAS.LioPA. Cost-effectiveness of prophylactic moisturization for atopic dermatitis. JAMA Pediatr. 2017;171(2):e163909.doi:10.1001/jamapediatrics.2016.3909
6.
van ZuurenEJ.FedorowiczZ.ChristensenR.LavrijsenA.ArentsBWM. Emollients and moisturisers for eczema. Cochrane Database Syst Rev. 2017;2017(2):CD012119.
7.
BrarKK.NicolNH.BoguniewiczM. Strategies for successful management of severe atopic dermatitis. J Allergy Clin Immunol. 2019;7(1):1-16.doi:10.1016/j.jaip.2018.10.021
8.
EichenfieldLF.AhluwaliaJ.WaldmanA.BorokJ.UdkoffJ.BoguniewiczM. Current guidelines for the evaluation and management of atopic dermatitis: acomparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. J Allergy Clin Immunol. 2017;139(4S):S49-S57.doi:10.1016/j.jaci.2017.01.009
9.
CardonaID.StillmanL.JainN. Does bathing frequency matter in pediatric atopic dermatitis?Ann Allergy, Asthma Immunol. 2016;117(1):9-13.doi:10.1016/j.anai.2016.05.014
10.
SanterM.RiddMJ.FrancisNAet al. Emollient Bath additives for the treatment of childhood eczema (BATHE): multicentre pragmatic parallel group randomised controlled trial of clinical and cost effectiveness. BMJ. 2018;361(8151):k1332.doi:10.1136/bmj.k1332
11.
AssarianZ.O’BrienTJ.NixonR. Soak and smear: an effective treatment for eczematous dermatoses. Australas J Dermatol. 2015;56(3):215-217.doi:10.1111/ajd.12300
12.
ChopraR.VakhariaPP.SacotteR.SilverbergJI. Efficacy of bleach baths in reducing severity of atopic dermatitis: a systematic review and meta-analysis. Ann Allergy, Asthma Immunol. 2017;119(5):435-440.doi:10.1016/j.anai.2017.08.289
13.
González-LópezG.Ceballos-RodríguezRM.González-LópezJJ.Feito RodríguezM.Herranz-PintoP. Efficacy and safety of wet wrap therapy for patients with atopic dermatitis: a systematic review and meta-analysis. Br J Dermatol. 2017;177(3):688-695.doi:10.1111/bjd.15165
14.
LimNR.LohmanME.LioPA. The role of elimination diets in atopic Dermatitis-A comprehensive review. Pediatr Dermatol. 2017;34(5):516-527.doi:10.1111/pde.13244
15.
Bath-HextallF.DelamereFM.WilliamsHC. Dietary exclusions for improving established atopic eczema in adults and children: systematic review. Allergy Eur J Allergy Clin Immunol. 2009;64(2):258-264.doi:10.1111/j.1398-9995.2008.01917.x
16.
SolmanL.Lloyd-LaveryA.GrindlayDJC.RogersNK.ThomasKS.HarmanKE. What's new in atopic eczema? an analysis of systematic reviews published in 2016. Part 1: treatment and prevention. Clin Exp Dermatol. 2019;44(4):363-369.doi:10.1111/ced.13885
17.
VaughnAR.FooladN.MaaroufM.TranKA.ShiVY. Micronutrients in atopic dermatitis: a systematic review. J Altern Complement Med. 2019;25(6):567-577.doi:10.1089/acm.2018.0363
OrelR.ReberšakLV. Clinical effects of prebiotics in pediatric population. Indian Pediatr. 2016;53(12):1083-1089.
20.
OuC-Y.KuoH-C.WangLet al. Prenatal and postnatal probiotics reduces maternal but not childhood allergic diseases: a randomized, double-blind, placebo-controlled trial. Clin Exp Allergy. 2012;42(9):1386-1396.doi:10.1111/j.1365-2222.2012.04037.x
21.
WollenbergA.BarbarotS.BieberTet al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. J Eur Acad Dermatol Venereol. 2018;32(6):850-878.doi:10.1111/jdv.14888
22.
BamfordJTM.RayS.MusekiwaA.van GoolC.HumphreysR.ErnstE. Oral evening primrose oil and borage oil for eczema. Cochrane Database Syst Rev. 2013;2013(4):CD004416.
23.
GuS.YangAWH.CCLXet al. Chinese herbal medicine for atopic eczema. Cochrane Database Syst Rev. 2013;2013(9):CD008642.
24.
VieiraBL.LimNR.LohmanME.LioPA. Complementary and alternative medicine for atopic dermatitis: an evidence-based review. Am J Clin Dermatol. 2016;17(6):557-581.doi:10.1007/s40257-016-0209-1
25.
KaragounisTK.GittlerJK.RotembergV.MorelKD. Use of “natural” oils for moisturization: review of olive, coconut, and sunflower seed oil. Pediatr Dermatol. 2019;36(1):9-15.doi:10.1111/pde.13621
26.
ShiK.LioPA. Alternative treatments for atopic dermatitis: an update. Am J Clin Dermatol. 2019;20(2):251-266.doi:10.1007/s40257-018-0412-3
SauderMB.McEvoyA.SampsonMet al. The effectiveness of written action plans in atopic dermatitis. Pediatr Dermatol. 2016;33(2):e151-e153.doi:10.1111/pde.12774
29.
KupferJ.GielerU.DiepgenTLet al. Structured education program improves the coping with atopic dermatitis in children and their parents-a multicenter, randomized controlled trial. J Psychosom Res. 2010;68(4):353-358.doi:10.1016/j.jpsychores.2009.04.014
30.
GilliamAE.MaddenN.SendowskiM.MioduszewskiM.DuderstadtKG. Use of eczema action plans (EAPs) to improve parental understanding of treatment regimens in pediatric atopic dermatitis (AD): a randomized controlled trial. J Am Acad Dermatol. 2016;74(2):375-377.doi:10.1016/j.jaad.2015.08.067
31.
ShelleyAJ.McDonaldKA.McEvoyAet al. Usability, satisfaction, and usefulness of an illustrated eczema action plan. J Cutan Med Surg. 2018;22(6):577-582.doi:10.1177/1203475418789028
32.
MatterneU.BöhmerMM.WeisshaarE.JupiterA.CarterB.ApfelbacherCJ. Oral H1 antihistamines as “add-on” therapy to topical treatment for eczema. Cochrane Database Syst Rev. 2019;2019(1):CD012167.
33.
SchwartzPJ.WoosleyRL. Predicting the unpredictable: drug-induced QT prolongation and torsades de pointes. J Am Coll Cardiol. 2016;67(13):1639-1650.doi:10.1016/j.jacc.2015.12.063
34.
EichenfieldLF.TomWL.BergerTGet al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-132.doi:10.1016/j.jaad.2014.03.023
35.
GlinesKR.StiffKM.FreezeM.ClineA.StrowdLC.FeldmanSR. An update on the topical and oral therapy options for treating pediatric atopic dermatitis. Expert Opin Pharmacother. 2019;20(5):621-629.doi:10.1080/14656566.2018.1561868
36.
MaybaJN.GooderhamMJ. Review of atopic dermatitis and topical therapies. J Cutan Med Surg. 2017;21(3):227-236.doi:10.1177/1203475416685077
37.
SigurgeirssonB.BoznanskiA.ToddGet al. Safety and efficacy of pimecrolimus in atopic dermatitis: a 5-year randomized trial. Pediatrics. 2015;135(4):597-606.doi:10.1542/peds.2014-1990
38.
LiuL.OngG. A randomized, open-label study to evaluate an intermittent dosing regimen of fluticasone propionate 0.05% cream in combination with regular emollient skin care in reducing the risk of relapse in pediatric patients with stabilized atopic dermatitis. J Dermatolog Treat. 2018;29(5):501-509.doi:10.1080/09546634.2017.1401211
39.
FukuieT.HirakawaS.NaritaMet al. Potential preventive effects of proactive therapy on sensitization in moderate to severe childhood atopic dermatitis: a randomized, investigator-blinded, controlled study. J Dermatol. 2016;43(11):1283-1292.doi:10.1111/1346-8138.13408
40.
HuangA.ChoC.LeungDYM.BrarK. Atopic dermatitis: early treatment in children. Curr Treat Options Allergy. 2017;4(3):355-369.doi:10.1007/s40521-017-0140-6
CallenJ.ChamlinS.EichenfieldLFet al. A systematic review of the safety of topical therapies for atopic dermatitis. Br J Dermatol. 2007;156(2):203-221.doi:10.1111/j.1365-2133.2006.07538.x
LePoidevinLM.LeeDE.ShiVY. A comparison of international management guidelines for atopic dermatitis. Pediatr Dermatol. 2019;36(1):36-65.doi:10.1111/pde.13678
45.
HonKL.TsangYCK.PongNHet al. Correlations among steroid fear, acceptability, usage frequency, quality of life and disease severity in childhood eczema. J Dermatolog Treat. 2015;26(5):418-425.doi:10.3109/09546634.2015.1025030
46.
HonKL.LeongKF.LeungTNH.LeungAKC. Dismissing the fallacies of childhood eczema management: case scenarios and an overview of best practices. Drugs Context. 2018;7:1-12.doi:10.7573/dic.212547
47.
HongE.SmithS.FischerG. Evaluation of the atrophogenic potential of topical corticosteroids in pediatric dermatology patients. Pediatr Dermatol. 2011;28(4):393-396.doi:10.1111/j.1525-1470.2011.01445.x
48.
HenggeUR.RuzickaT.SchwartzRA.CorkMJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006;54(1):1-15.doi:10.1016/j.jaad.2005.01.010
RemitzA.De PitàO.MotaA.Serra-BaldrichE.VakirlisE.KappA. Position statement: topical calcineurin inhibitors in atopic dermatitis. J Eur Acad Dermatol Venereol. 2018;32(12):2074-2082.doi:10.1111/jdv.15272
51.
HuangX.XuB. Efficacy and safety of tacrolimus versus pimecrolimus for the treatment of atopic dermatitis in children: a network meta-analysis. Dermatology. 2015;231(1):41-49.doi:10.1159/000381948
52.
SiegfriedEC.JaworskiJC.KaiserJD.HebertAA. Systematic review of published trials: long-term safety of topical corticosteroids and topical calcineurin inhibitors in pediatric patients with atopic dermatitis. BMC Pediatr. 2016;16(1):75.doi:10.1186/s12887-016-0607-9
53.
LyndeCW.BergmanJ.FiorilloLet al. Clinical insights about topical treatment of mild-to-moderate pediatric and adult atopic dermatitis. J Cutan Med Surg. 2019;23(3_suppl):3S-13.doi:10.1177/1203475419843108
54.
MargolisDJ.AbuabaraK.HoffstadOJ.WanJ.RaimondoD.BilkerWB. Association between malignancy and topical use of pimecrolimus. JAMA Dermatol. 2015;151(6):594-599.doi:10.1001/jamadermatol.2014.4305
55.
CastellsagueJ.KuiperJG.PottegårdAet al. A cohort study on the risk of lymphoma and skin cancer in users of topical tacrolimus, pimecrolimus, and corticosteroids (Joint European Longitudinal Lymphoma and Skin Cancer Evaluation - JOELLE study). Clin Epidemiol. 2018;10:299-310.doi:10.2147/CLEP.S146442
56.
SiegfriedEC.JaworskiJC.HebertAA. Topical calcineurin inhibitors and lymphoma risk: evidence update with implications for daily practice. Am J Clin Dermatol. 2013;14(3):163-178.doi:10.1007/s40257-013-0020-1
57.
EichenfieldLF.CallRS.ForshaDWet al. Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis. J Am Acad Dermatol. 2017;77(4):641-649.doi:10.1016/j.jaad.2017.06.010
58.
Stein GoldLF.SpelmanL.SpellmanMC.HughesMH.ZaneLT. A phase 2, randomized, controlled, dose-ranging study evaluating Crisaborole Topical Ointment, 0.5% and 2% in adolescents with mild to moderate atopic dermatitis. J Drugs Dermatol. 2015;14(12):1394-1399.
59.
TomWL.Van SyocM.ChandaS.ZaneLT.ProfileP. Pharmacokinetic profile, safety, and tolerability of crisaborole topical ointment, 2% in adolescents with atopic dermatitis: an open-label phase 2a study. Pediatr Dermatol. 2016;33(2):150-159.doi:10.1111/pde.12780
60.
PallerAS.TomWL.LebwohlMGet al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494-503.doi:10.1016/j.jaad.2016.05.046
61.
RamachandranV.ClineA.FeldmanSR.StrowdLC. Evaluating crisaborole as a treatment option for atopic dermatitis. Expert Opin Pharmacother. 2019;20(9):1057-1063.doi:10.1080/14656566.2019.1604688
62.
MokZ-R.KohMJ-A.ChongW-S. Is phototherapy useful in the treatment of atopic dermatitis in Asian children? A 5-year report from Singapore. Pediatr Dermatol. 2014;31(6):698-702.doi:10.1111/pde.12405
63.
DayalS.PathakK.SahuP.JainVK. Narrowband UV-B phototherapy in childhood atopic dermatitis: efficacy and safety. An Bras Dermatol. 2017;92(6):801-806.doi:10.1590/abd1806-4841.20175958
64.
DarnéS.LeechSN.TaylorAEM. Narrowband ultraviolet B phototherapy in children with moderate-to-severe eczema: a comparative cohort study. Br J Dermatol. 2014;170(1):150-156.doi:10.1111/bjd.12580
65.
CrallCS.RorkJF.DelanoS.HuangJT. Phototherapy in children: considerations and indications. Clin Dermatol. 2016;34(5):633-639.doi:10.1016/j.clindermatol.2016.05.018
66.
WollenbergA.OranjeA.DeleuranMet al. ETFAD/EADV eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients. J Eur Acad Dermatol Venereol. 2016;30(5):729-747.doi:10.1111/jdv.13599
67.
ProudfootLE.PowellAM.AyisSet al. The European treatment of severe atopic eczema in children taskforce (TREAT) survey. Br J Dermatol. 2013;169(4):901-909.doi:10.1111/bjd.12505
68.
TotriCR.EichenfieldLF.LoganKet al. Prescribing practices for systemic agents in the treatment of severe pediatric atopic dermatitis in the US and Canada: the PeDRA TREAT survey. J Am Acad Dermatol. 2017;76(2):281-285.doi:10.1016/j.jaad.2016.09.021
69.
El-KhalawanyMA.HassanH.ShaabanD.GhonaimN.EassaB. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. Eur J Pediatr. 2013;172(3):351-356.doi:10.1007/s00431-012-1893-3
70.
ColmeneroCG.MorenteGB.SánchezJT. Oral cyclosporine weekend therapy: a new maintenance therapeutic option in patients with severe atopic dermatitis. Pediatr Dermatol. 2015;32(4):551-552.doi:10.1111/pde.12592
71.
SibbaldC.PopeE.HoN.WeinsteinM. Retrospective review of relapse after systemic cyclosporine in children with atopic dermatitis. Pediatr Dermatol. 2015;32(1):36-40.doi:10.1111/pde.12367
72.
Hernández-MartínA.Noguera-MorelL.Bernardino-CuestaBet al. Cyclosporine A for severe atopic dermatitis in children. efficacy and safety in a retrospective study of 63 patients. J Eur Acad Dermatol Venereol. 2017;31(5):837-842.doi:10.1111/jdv.14066
73.
SarıcaoğluH.YaziciS.ZorluÖzge.Bülbül BaşkanE.AydoğanK. Cyclosporine-A for severe childhood atopic dermatitis: clinical experience on efficacy and safety profile. Turk J Med Sci. 2018;48(5):933-938.doi:10.3906/sag-1711-7
74.
TsakokT.FlohrC. Methotrexate vs. ciclosporin in the treatment of severe atopic dermatitis in children: a critical appraisal. Br J Dermatol. 2014;170(3):496-498.doi:10.1111/bjd.12820
75.
DeoM.YungA.HillS.RademakerM. Methotrexate for treatment of atopic dermatitis in children and adolescents. Int J Dermatol. 2014;53(8):1037-1041.doi:10.1111/ijd.12314
76.
DvorakovaV.O'ReganGM.IrvineAD. Methotrexate for severe childhood atopic dermatitis: clinical experience in a tertiary center. Pediatr Dermatol. 2017;34(5):528-534.doi:10.1111/pde.13209
77.
TaiebY.BaumS.Ben AmitaiD.BarzilaiA.GreenbergerS. The use of methotrexate for treating childhood atopic dermatitis: a multicenter retrospective study. J Dermatolog Treat. 2019;30(3):240-244.doi:10.1080/09546634.2018.1508816
78.
Noguera-MorelL.KnöpfelN.TorreloA.Hernández-MartínA. A retrospective study of systemic treatment of severe atopic dermatitis with azathioprine: effectiveness and tolerance in 11 pediatric patients. Actas Dermo-Sifiliográficas. 2019;110(3):227-231.doi:10.1016/j.adengl.2018.06.027
79.
FuggleNR.BragoliW.MahtoA.GloverM.MartinezAE.KinslerVA. The adverse effect profile of oral azathioprine in pediatric atopic dermatitis, and recommendations for monitoring. J Am Acad Dermatol. 2015;72(1):108-114.doi:10.1016/j.jaad.2014.08.048
80.
CaufieldM.TomWL. Oral azathioprine for recalcitrant pediatric atopic dermatitis: clinical response and thiopurine monitoring. J Am Acad Dermatol. 2013;68(1):29-35.doi:10.1016/j.jaad.2012.07.001
81.
MurphyL-A.AthertonD. A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Br J Dermatol. 2002;147(2):308-315.doi:10.1046/j.1365-2133.2002.04922.x
82.
HonK-LE.ChingGKW.LeungT-F.ChowC-M.LeeKKC.NgP-C.K-LEH. Efficacy and tolerability at 3 and 6 months following use of azathioprine for recalcitrant atopic dermatitis in children and young adults. J Dermatolog Treat. 2009;20(3):141-145.doi:10.1080/09546630802512646
83.
DruckerAM.EyerichK.de Bruin-WellerMSet al. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol. 2018;178(3):768-775.doi:10.1111/bjd.15928
84.
SimpsonEL.PallerAS.SiegriedECet al. Dupilumab efficacy and safety in adolescents with moderate-to-severe atopic dermatitis: results from a multicenter, randomized, placebo-controlled, double-blind, parallel-group, phase 3 study. In: 27th EADV Congress, September 12-16, 2018. Paris, France: Abstract #4640; 2018.
85.
TreisterAD.LioPA. Long-term off-label dupilumab in pediatric atopic dermatitis: a case series. Pediatr Dermatol. 2019;36(1):85-88.doi:10.1111/pde.13697
86.
SiegfriedEC.IgelmanS.JaworskJCet al. Use of dupilimab in pediatric atopic dermatitis: access, dosing, and implications for managing severe atopic dermatitis. Pediatr Dermatol. 2019;36(1):172-176.doi:10.1111/pde.13707
87.
SimpsonEL.BieberT.Guttman-YasskyEet al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335-2348.doi:10.1056/NEJMoa1610020
88.
ThyssenJP.de Bruin-WellerMS.PallerASet al. Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion. J Eur Acad Dermatol Venereol. 2019;33(7):1224-1231.doi:10.1111/jdv.15608
AlbaderSS.AlharbiAA.AleneziRF.AlsaifFM. Dupilumab side effect in a patient with atopic dermatitis: a case report study. Biologics. 2019;13:79-82.doi:10.2147/BTT.S195512