Abstract: Herbal medicine is widely used for dermatological diseases, particularly atopic dermatitis. This study aims to systematically review existing literature on the efficacy of both topical and systemic herbal interventions for atopic dermatitis across various age groups.
Conducting a comprehensive search on MEDLINE/PubMed, Scopus, and the Cochrane Central Register of Controlled Trials (Central) until April 12, 2023, only randomized controlled trials (RCTs) were included.
The review is reported following the PRISMA guidelines and was conducted in accordance to Cochrane recommendations. Two authors independently extracted details, including demographics, medication, control/placebo groups, outcomes, adverse events, and results, with quality assessment using the Cochrane risk of bias tool 2.0. A meta-analysis, utilizing the random-effects model, was conducted, and publication bias was assessed through funnel plot inspection. The quality of evidence adhered to GRADE working group recommendations.
The primary focus was evaluating atopic dermatitis or pruritus severity. The review encompassed 51 RCTs (3763 participants). Of these, 31 RCTs explored 19 distinct herbs and five complex remedies, whereas 20 RCTs (1088 participants) specifically investigated evening primrose oil (EPO). Herbs such as sunflower, licorice, figs, coconut, EPO, indigo naturalis, licorice, mauve, St. John’s wort, and a combination of aloe vera and olive oil were found to have evidence of efficacy in the local treatment of atopic dermatitis. A meta-analysis on systemic used EPO, involving 13 RCTs, found no significant difference in atopic dermatitis severity compared with placebo (SMD: 0.14; 95% CI [−0.45; 0.73], 13 RCTs).
In conclusion, this review provides a nuanced perspective on herbal substance efficacy for atopic dermatitis. While the EPO meta-analysis failed to show a discernible benefit beyond placebo, individual herbal preparations showed promising results in RCTs included in this review. Nevertheless, larger, methodologically rigorous studies are essential to establish evidence for herbal remedies in atopic dermatitis treatment.
MandlikDS, MandlikSK. Atopic dermatitis: New insight into the etiology, pathogenesis, diagnosis and novel treatment strategies. Immunopharmacol Immunotoxicol. 2021; 43(2):105–125; doi: 10.1080/08923973.2021.1889583
3.
TorresT, FerreiraEO, GonçaloM, et al.Update on atopic dermatitis. Acta Med Port. 2019; 32(9):606–613; doi: 10.20344/amp.11963
4.
BamfordJTM, RayS, MusekiwaA, et al.Oral evening primrose oil and borage oil for eczema. Cochrane Database Syst Rev. 2013; 2013(4):CD004416; doi: 10.1002/14651858.CD004416.pub2
5.
HughesR, WardD, TobinAM, et al.The use of alternative medicine in pediatric patients with atopic dermatitis. Pediatr Dermatol. 2007; 24(2):118–120; doi: 10.1111/j.1525-1470.2007.00355.x
6.
LandisET, DavisSA, FeldmanSR, et al.Complementary and alternative medicine use in dermatology in the United States. J Altern Complement Med. 2014; 20(5):392–398; doi: 10.1089/acm.2013.0327
7.
ThandarY, GrayA, BothaJ, et al.Topical herbal medicines for atopic eczema: A systematic review of randomized controlled trials. Br J Dermatol. 2017; 176(2):330–343; doi: 10.1111/bjd.14840
8.
HussainZ, ThuHE, ShuidAN, et al.Phytotherapeutic potential of natural herbal medicines for the treatment of mild-to-severe atopic dermatitis: A Review of Human Clinical Studies. Biomed Pharmacother. 2017; 93:596–608; doi: 10.1016/j.biopha.2017.06.087
9.
VieiraBL, LimNR, LohmanME, et al.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
10.
Adler-NealAL, ClineA, FrantzT, et al.Complementary and integrative therapies for childhood atopic dermatitis. Children (Basel). 2019; 6(11):121; doi: 10.3390/children6110121
11.
KwonCY, LeeB, KimS, et al.Effectiveness and safety of herbal medicine for atopic dermatitis: An overview of systematic reviews. Evid Based Complement Alternat Med. 2020; 2020(1):4140692; doi: 10.1155/2020/4140692
12.
MoherD, LiberatiA, TetzlaffJ, et al.Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009; 6(7):e1000097; doi: 10.1371/journal.pmed.1000097
13.
HigginsJP, ThomasJ, ChandlerJ, CumpstonM, LiT, PageMJ, WelchVA., editor. Cochrane handbook for systematic reviews of interventions version 6.2 (updated february 2021). Cochrane, 2021. Available from: https://training.cochrane.org/handbook.
14.
SchwarzerG, CarpenterJR, RückerG. Meta-Analysis with R. Springer: Cham; 2015. EBL-Schweitzer.
15.
CornellJE, MulrowCD, LocalioR, et al.Random-effects meta-analysis of inconsistent effects: A time for change. Ann Intern Med. 2014; 160(4):267–270; doi: 10.7326/M13-2886
16.
IntHoutJ, IoannidisJPA, BormGF. The hartung-knapp-sidik-jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard dersimonian-laird method. BMC Med Res Methodol. 2014; 14:25; doi: 10.1186/1471-2288-14-25
17.
KnappG, HartungJ. Improved tests for a random effects meta-regression with a single covariate. Stat Med. 2003; 22(17):2693–2710; doi: 10.1002/sim.1482
18.
RöverC, KnappG, FriedeT. Hartung-knapp-sidik-jonkman approach and its modification for random-effects meta-analysis with few studies. BMC Med Res Methodol. 2015; 15:99; doi: 10.1186/s12874-015-0091-1
19.
CohenJ. Statistical Power Analysis for the Behavioral Sciences. 2. Ed: Erlbaum; Hillsdale, NJ; 1988.
20.
BorensteinM, HedgesLV, HigginsJPT, et al.Introduction to Meta-Analysis Statistics in Practice. John Wiley & Sons: Chichester, U.K; 2009; doi: 10.1002/9780470743386
21.
HigginsJPT, ThompsonSG, DeeksJJ, et al.Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414):557–560; doi: 10.1136/bmj.327.7414.557
22.
EvangelistaMTP, Abad-CasintahanF, Lopez-VillafuerteL. The effect of topical virgin coconut oil on SCORAD index, transepidermal water loss, and skin capacitance in mild to moderate pediatric atopic dermatitis: A randomized, double-blind, clinical trial. Int J Dermatol. 2014; 53(1):100–108; doi: 10.1111/ijd.12339
23.
SomjornP, KamanamoolN, KanokrungseeS, et al.A cream containing linoleic acid, 5% dexpanthenol and ceramide in the treatment of atopic dermatitis. Asian Pac J Allergy Immunol. 2021; doi: 10.12932/AP-221220-1021
24.
FinlayAY, MarksR, WilsonAM, et al.Epogam in Children with atopic eczema. [(unpublished data only)]; 2001; 1–473.
25.
HarperJ, JaderbergM, WilsonA. Efamol in moderate to severe atopic eczema: (unpublished data only); 2001; [SN 890136/7].
26.
PanahiY, RastgarN, ZamaniA, et al.Comparing the therapeutic effects of aloe vera and olive oil combination cream versus topical betamethasone for atopic dermatitis: A randomized double-blind clinical trial. J Pharmacopuncture. 2020; 23(3):173–178; doi: 10.3831/KPI.2020.23.3.173
27.
AnsteyA, QuigleyM, WilkinsonJD. Topical evening primrose oil as treatment for atopic eczema. J Dermatolog Treat. 1990; 1(4):199–201; doi: 10.3109/09546639009086732
28.
SchemppCM, WindeckT, HezelS, et al.Topical treatment of atopic dermatitis with St. John’s wort cream - A randomized, placebo controlled, double blind half-side comparison. Phytomedicine. 2003; 10(SUPPL. 4):31–37; doi: 10.1078/1433-187X-00306
29.
de BelilovskyC, Roo-RodriguezE, BaudouinC, et al.Natural peroxisome proliferator-activated receptor-alpha agonist cream demonstrates similar therapeutic response to topical steroids in atopic dermatitis. J Dermatolog Treat. 2011; 22(6):359–365; doi: 10.3109/09546634.2010.499932
30.
KiehlR, IonescuG, ManuelP, et al.Clinical, immuno- and lipid modulating effects of unsaturated fatty acids in patients with atopic eczema; [KLINISCHE, IMMUN- UND LIPIDMODULATORISCHE EFFEKTE EINER BEHANDLUNG MIT UNGESATTIGTEN FETTSAUREN BEI ATOPISCHER DERMATITIS]. H. + G Zeitschrift Fur Hautkrankheiten. 1994; 69(1):42–48. Available from: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028069291&partnerID=40&md5=0afc9f0eb6e8d044473a9086fc66d898
31.
LandiG. Oral administration of borago oil in atopic dermatitis. J Appl Cosmetol. 1993; 11(4):115–120; doi: 10.1002/central/CN-01081486/full Record #414 of 1521
32.
BamfordJT, GibsonRW, RenierCM. Atopic eczema unresponsive to evening primrose oil (linoleic and gamma-linolenic acids). J Am Acad Dermatol. 1985; 13(6):959–965; doi: 10.1016/s0190-9622(85)70245-9
BiagiPL, BordoniA, HreliaS, et al.The effect of gamma-linolenic acid on clinical status, red cell fatty acid composition and membrane microviscosity in infants with atopic dermatitis. Drugs Exp Clin Res. 1994; 20(2):77–84.
35.
Fraser. Efamol in Atopic Eczema: (unpublished data only); 2001 (22 October); [ISSN 86004/5/6/7].
36.
HederosC-A, BergA. Epogam evening primrose oil treatment in atopic dermatitis and asthma. Arch Dis Child. 1996; 75(6):494–497; doi: 10.1136/adc.75.6.494
37.
MacKieR. A Clinical and Mechanistic Assessment of Eamol Evening Primrose Oil in Atopic Eczema (Adults): (unpublished data only); 2001; [ISN 890054].
38.
MacKieR. A clinical and mechanistic assessment of efamol evening primrose oil in atopic eczema in Children: (unpublished data only); 2001; [ISN 890067].
39.
Schalin-KarrilaM, MattilaL, JansenCT, et al.Evening primrose oil in the treatment of atopic eczema: Effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol. 1987; 117(1):11–19; doi: 10.1111/j.1365-2133.1987.tb04085.x
40.
WishartJ, MacdonaldK, OakleyA. A Multi-center Assessment of Efamol Evening Primrose Oil in Severe Atopic Eczema: (unpublished data only); 2001 (October); [ISN 900196/197/198].
41.
van GoolCJAW, ThijsC, HenquetCJM, et al.Gamma-linolenic acid supplementation for prophylaxis of atopic dermatitis‐a randomized controlled trial in infants at high familial risk. Am J Clin Nutr. 2003; 77(4):943–951; doi: 10.1093/ajcn/77.4.943
42.
AbbasiS, KamalinejadM, BabaieD, et al.A new topical treatment of atopic dermatitis in pediatric patients based on ficus carica L. (Fig.): A randomized, placebo-controlled clinical trial. Complement Ther Med. 2017; 35:85–91; doi: 10.1016/j.ctim.2017.10.003
43.
LinY-K, ChangS-H, YangC-Y, et al.Efficacy and safety of indigo naturalis ointment in treating atopic dermatitis: A randomized clinical trial. J Ethnopharmacol. 2020; 250:112477; doi: 10.1016/j.jep.2019.112477
44.
ScharioM, LünnemannL, StrouxA, et al.Children with dry skin and atopic predisposition: Daily use of emollients in a participant-blinded, randomized, prospective trial. Skin Pharmacol Physiol. 2014; 27(4):208–216; doi: 10.1159/000360546
45.
NaseriV, ChavoshzadehZ, MizaniA, et al.Effect of topical marshmallow (Althaea officinalis) on atopic dermatitis in children: A pilot double-blind active-controlled clinical trial of an in-silico-analyzed phytomedicine. Phytother Res. 2021; 35(3):1389–1398; doi: 10.1002/ptr.6899
46.
WananukulS, ChatproedpraiS, CharutragulchaiW. Randomized, double-blind, split-side comparison study of moisturizer containing licochalcone vs. 1% hydrocortisone in the treatment of infantile seborrhoeic dermatitis. J Eur Acad Dermatol Venereol. 2012; 26(7):894–897; doi: 10.1111/j.1468-3083.2011.04187.x
47.
WangS, WangL, LiP, et al.The improvement of infantile atopic dermatitis during the maintenance period: A multicenter, randomized, parallel controlled clinical study of emollients in Prinsepia utilis Royle. Dermatol Ther. 2020; 33(2):e13153; doi: 10.1111/dth.13153
48.
MeysamiM, HashempurMH, KamalinejadM, et al.Efficacy of short term topical malva sylvestris l. cream in pediatric patients with atopic dermatitis: A randomized double-blind placebo-controlled clinical trial. Endocr Metab Immune Disord Drug Targets. 2021; 21(9):1673–1678; doi: 10.2174/1871530320666201023125411
49.
ChungBY, ParkSY, JungMJ, et al.Effect of evening primrose oil on Korean patients with mild atopic dermatitis: A randomized, double-blinded, placebo-controlled clinical study. Ann Dermatol. 2018; 30(4):409–416; doi: 10.5021/ad.2018.30.4.409
50.
France, et al.Epogam in severe atopic eczema.: (unpublished data only); 2001 (18 October); [ISN 880002/3/4/24/25/128/130/890141].
51.
KenicerK, KeczkesK, GreenC, et al.Evening primrose oil in the treatment of atopic dermatitis: A Placebo-Controlled Study: (unpublished data only); 2001; [ISN: 900210/910098].
52.
KovarIZ, WrightS. An assessment of efamol evening primrose oil in moderate to severe atopic eczema in young children: (unpublished data only); [ISN 900158].
53.
MacLeodA, MischKJ. A comparative assessment of efamol evening primrose oil and efamol marine in severe atopic eczema: (unpublished data only); [ISN 89100].
54.
LinnamaaP, SavolainenJ, KouluL, et al.Blackcurrant seed oil for prevention of atopic dermatitis in newborns: A randomized, double-blind, placebo-controlled trial. Clin Exp Allergy. 2010; 40(8):1247–1255; doi: 10.1111/j.1365-2222.2010.03540.x
55.
CallawayJ, SchwabU, HarvimaI, et al.Efficacy of dietary hempseed oil in patients with atopic dermatitis. J Dermatolog Treat. 2005; 16(2):87–94; doi: 10.1080/09546630510035832
56.
SenapatiS, BanerjeeS, GangopadhyayD. Evening primrose oil is effective in atopic dermatitis: A randomized placebo-controlled trial. Indian J Dermatol Venereol Leprol. 2008; 74(5):447–452; doi: 10.4103/0378-6323.42645
57.
KaneharaS, OhtaniT, UedeK, et al.Clinical effects of undershirts coated with borage oil on children with atopic dermatitis: A double-blind, placebo-controlled clinical trial. J Dermatol. 2007; 34(12):811–815; doi: 10.1111/j.1346-8138.2007.00391.x
58.
MoriK, SekiT, KaizuK, et al.Efficacy of a moisturizer containing a pseudo-ceramide and a eucalyptus extract for Japanese patients with mild atopic dermatitis in the summer. J Cosmet Dermatol. 2019; 18(3):850–856; doi: 10.1111/jocd.12735
59.
KortingHC, Schäfer-KortingM, KlövekonW, et al.Comparative efficacy of hamamelis distillate and hydrocortisone cream in atopic eczema. Eur J Clin Pharmacol. 1995; 48(6):461–465; doi: 10.1007/BF00194335
60.
SaeediM, Morteza-SemnaniK, GhoreishiM-R. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat. 2003; 14(3):153–157; doi: 10.1080/09546630310014369
61.
MainzerC, Le GuillouM, VyumvuhoreR, et al.Clinical efficacy of oligofructans from ophiopogon japonicus in reducing atopic dermatitis flare-ups in caucasian patients. Acta Derm Venereol. 2019; 99(10):858–864; doi: 10.2340/00015555-3224
62.
GrimaltR, MengeaudV, CambazardF. The steroid-sparing effect of an emollient therapy in infants with atopic dermatitis: A randomized controlled study. Dermatology. 2007; 214(1):61–67; doi: 10.1159/000096915
63.
HenzBM, JablonskaS, van de KerkhofPC, et al.Double-blind, multicentre analysis of the efficacy of borage oil in patients with atopic eczema. Br J Dermatol. 1999; 140(4):685–688; doi: 10.1046/j.1365-2133.1999.02771.x
64.
Berth-JonesJ, Graham-BrownR. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis. Lancet. 1993; 341(8860):1557–1560; doi: 10.1016/0140-6736(93)90697-F
65.
BordoniA, BiagiPL, MasiM, et al.Evening primr ose oil (Efamol) in the treatment of children with atopic eczema. Drugs under Exp Clin Res. 1988; 14(4):291–297.
YangB, KalimoKO, MattilaLM, et al.Effects of dietary supplementation with sea buckthorn (Hippophae rhamnoides) seed and pulp oils on atopic dermatitis. J Nutr Biochem. 1999; 10(11):622–630; doi: 10.1016/S0955-2863(99)00049-2
68.
MsikaP, BelilovskyC, de PiccardiN, et al.New emollient with topical corticosteroid-sparing effect in treatment of childhood atopic dermatitis: SCORAD and quality of life improvement. Pediatr Dermatol. 2008; 25(6):606–612; doi: 10.1111/j.1525-1470.2008.00783.x
AndersonC, Lis-BalchinM, Kirk-SmithM. Evaluation of massage with essential oils on childhood atopic eczema. Phytother Res. 2000; 14(6):452–456; doi: 10.1002/1099-1573(200009)14:6<452:aid-ptr952>3.0.co;2-4
71.
BorrekS, HildebrandtA, ForsterJ. Borage seed-oil and atopic dermatitis; [Gammalinolensaure-reiche Borretschsamenol-Kapseln bei Kindern mit Atopischer Dermatitis]. Klin Padiatr. 1997; 209(3):100–104; doi: 10.1055/s-2008-1043936
72.
ShapiraMY, RaphaelovichY, GiladL, et al.Treatment of atopic dermatitis with herbal combination of eleutherococcus, Achillea millefolium, and Lamium album has no advantage over placebo: A double blind, placebo-controlled, randomized trial. J Am Acad Dermatol. 2005; 52(4):691–693; doi: 10.1016/j.jaad.2003.05.008
73.
WangM-C, ChouY-T, KaoM-C, et al.Topical chinese herbal medicine in treating atopic dermatitis (eczema): A systematic review and meta-analysis with core herbs exploration. J Ethnopharmacol. 2023; 317:116790; doi: 10.1016/j.jep.2023.116790
74.
CaiX, SunX, LiuL, et al.Efficacy and safety of Chinese herbal medicine for atopic dermatitis: Evidence from eight high-quality randomized placebo-controlled trials. Front Pharmacol. 2022; 13:927304; doi: 10.3389/fphar.2022.927304
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