Probiotics in the Treatment of Atopic Dermatitis

Question
Are probiotics helpful in the treatment and the prevention of atopic dermatitis?

Answers
From the Editor: A new feature of Ask the World Experts is involving WAO Junior Members in this endeavor.  Professors Manuel Rial Prado and Denica Zheleva both address the question of the role of probiotics in the treatment of atopic dermatitis.  While it appears probiotics may indeed prevent the development of atopic dermatitis, the role in treatment is uncertain.

July 5, 2023
By Dr. Crhistian Toribio

As previously described, atopic dermatitis (AD) is a chronic inflammatory skin disease affecting mainly the pediatric population and commonly associated with atopic diseases such as food allergy or asthma (1). Pruritus is responsible for much of the disease burden for patients and their families, significantly impacting their quality of life (2, 3). The main treatment modalities include topical anti-inflammatory medications and skin moisturization; however, depending on the severity, patients may require systemic therapy such as biologics or immunosuppressive drugs (4).

Our understanding of the underlying pathophysiologic mechanisms of AD has changed over the last decade. Multiple factors are involved in the pathogenesis, such as genetics, atopy, impaired skin barrier, dysregulated immune function, and dysbiosis in the gut and/or skin (5). Microbial imbalance has been an essential emphasis over the last few years, as probiotics could potentially restore a healthy microbiome and be used to prevent and treat allergic diseases (6).

Although the use of probiotics is promising, current clinical research doesn't fully support its use in prevention and treatment.

In children, two recent meta-analyses, including only double-blind placebo-controlled clinical trials (DBPCCT), evaluated probiotics' effect as prevention and treatment. Wang et al. analyzed the effect of prevention therapy (7). They found studies mostly did an intervention prenatal (> 36 weeks of gestational age) and postnatally, with Lactobacillus rhamnosus as the most commonly studied single strain. The intervention significantly affected AD prevention; however, the studies had high heterogeneity. Subgroup analysis showed that probiotics were effective when the intervention recipients were mothers and infants, when the timing of the intervention was prenatal and postpartum, when probiotics used were Lactobacillus rhamnosus and mixed strains, and when the follow-up time was less than 2 years. On the other hand, Fijan et al. determined whether the supplementation with single-strain lactobacilli for treating AD in children decreases the SCORAD index (8). Most studies investigated Lacticaseibacillus (Lactobacillus) rhamnosus GG; supplementation was mainly done for 3 or 4 months. Findings showed a significant decrease in the SCORAD index but with high heterogeneity between the studies. Subgroup analysis showed that Limosilactobacillus fermentum was the most effective strain with low heterogeneity between the studies, treatment was effective if it was done for 12 weeks (high heterogeneity), effective on patients with mild to moderate disease (high heterogeneity), and no difference in children under 4 years but effective if children under 1-year consumed Lactobacillus rhamnosus GG effect for 3 months.

Similarly, two recent meta-analyses evaluated the effect of probiotics as treatment in adult patients with AD. Umborowati et al. found probiotics can improve severity in patients with moderate AD, evidenced by decreased SCORAD index; however, studies had high heterogeneity, and no significant difference was noted in the skin and itch severity category of SCORAD, in quality of life, and IL-4, IFN-γ and IgE levels (9). Li et al. evaluated the effect in the short-term (< 4 weeks) and long-term (> 8 weeks) after probiotics administration (10). Their findings were decreased severity in the short term and long term but with high heterogeneity. Subgroup analysis showed decreased severity based on SCORAD and better effect with oral and mixed probiotics in the short term, while decreased severity and oral and single strain probiotics in the long term. They also found that a mixture of Lactobacillus salivarius (LS01) and Bifidobacterium (BR03) have a high probability of best supplementation in the short and long term. However, the studies had a high heterogeneity, including in the subgroup analysis.

Interestingly, most studies included were from Europe and Asia, consistent with previous research/meta-analyses results but with high heterogeneity. This effect could be due to several factors, including different intervention subjects, intervention timing, probiotic dosage, different probiotic strains, age of intervention, geographical region, the severity of AD, and the measurement of clinical outcomes. Therefore, more data still needs to be to determine probiotics' overall efficacy as prevention and treatment in children and adults.

References

1. Ständer S. Atopic dermatitis. N Engl J Med. 2021;384(12):1136-43.
2. Neri I, Galli E, Baiardini I, Picozza M, Rossi AB, Matruglio P, et al. Implications of atopic dermatitis on the quality of life of 6-11 years old children and caregivers (PEDI-BURDEN). J Asthma Allergy. 2023;16:383-96.
3. Fasseeh AN, Elezbawy B, Korra N, Tannira M, Dalle H, Aderian S, et al. Burden of atopic dermatitis in adults and adolescents: a systematic literature review. Dermatol Ther (Heidelb). 2022;12(12):2653-68.
4. Bieber T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov. 2022;21(1):21-40.
5. Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: Clinical implications. Allergy Asthma Proc. 2019;40(2):84-92.
6. Arkwright PD, Koplin JJ. Impact of a decade of research into atopic dermatitis. J Allergy Clin Immunol Pract. 2023;11(1):63-71.
7. Wang F, Wu F, Chen H, Tang B. The effect of probiotics in the prevention of atopic dermatitis in children: a systematic review and meta-analysis. Transl Pediatr. 2023;12(4):731-48. 
8. Fijan S, Kolč N, Hrašovec M, Jamtvedt G, Pogačar MŠ, Mičetić Turk D, Maver U. Single-strain probiotic Lactobacilli for the treatment of atopic dermatitis in children: A systematic review and meta-analysis. Pharmaceutics. 2023;15(4):1256.
9. Umborowati MA, Damayanti D, Anggraeni S, Endaryanto A, Surono IS, Effendy I, Prakoeswa CRS. The role of probiotics in the treatment of adult atopic dermatitis: a meta-analysis of randomized controlled trials. J Health Popul Nutr. 2022;41(1):37.
10. Li Y, Zhang B, Guo J, Cao Z, Shen M. The efficacy of probiotics supplementation for the treatment of atopic dermatitis in adults: a systematic review and meta-analysis. J Dermatolog Treat. 2022;33(6):2800-9.

Author
Crhistian Toribio, MD
Allergy and Clinical Immunology

10 October 2016
By Professor Manuel Rial Prado

Atopic dermatitis is the point of attachment between allergic diseases and autoimmune diseases. Probiotics and synbiotics favor the expression of anti-inflammatory Th1 cytokines which produces therapeutic benefits in patients with atopic dermatitis as revealed by recent meta-analysis.

On the other hand, the McMaster University with The WAO guideline panel suggests using probiotics in pregnant women and in breastfeed women at high risk for allergy in their children because considering all critical outcomes, there is a net benefit resulting primarily from prevention of eczema, they make the same recommendation in infants at high risk of developing allergies.

References:

1- World Allergy Organization Journal 2015; 8:4. DOI: 10.1186/s40413-015-0055-2.

2- JAMA Pediatr. 2016 Mar;170(3):236-42. doi: 10.1001/jamapediatrics.2015.3943

Manuel Rial Prado, MD
Allergist
Complexo Hospitalario Universitario A Coruña
A Coruña, Spain

By Professor Denica Zheleva

Atopic dermatitis is one of the epidemically expanding non-infectious diseases in the 21 century. It poses immense challenges to both patients and physicians. With a steady growth in its incidence and prevalence, the disease carries a heavy social and economic burden.

Atopic dermatitis (AD, syn. ‘atopic eczema’) is the commonest inflammatory skin disorder in children and represents a serious problem for the providers of health care all over the world (1-4) with an impressive effect on patients' quality of life (1),(5-9). In 40–60% of paediatric patients with AD persist having symptoms later on in life (10, 11). Although AD often starts in early infancy, there are adult onset forms  which start in adolescence or adulthood (11). Most of the patients with AD can control their skin disease with topical therapy and emollient skin care. There is a considerable group of patients with severe AD who do not respond to the prescribed treatment with moisturizers, topical corticosteroids (TCS), and/or topical calcineurin inhibitors (TCI) or experience immediate flare-ups after tapering topical anti-inflammatory therapy.

Probiotics and prebiotics appear to be effective in reducing the incidence of atopic dermatitis in infants, but their role in atopic dermatitis treatment is controversial (13). The clinical research supporting the use of probiotics for the treatment and prevention of AD are very limited. The positive effect may be related to the type of probiotic strain used, the method of administration, onset time, as well as the dose size and duration of treatment (12).  Based on current systematic review evidence, the most promising intervention for the prevention of AD is the use of probiotics (and possibly prebiotics) during the late stages of pregnancy and early life (14-15).

Most of the conducted studies concluded that the incidence of AD was lower in the probiotic administered cases than the controls. They reported less episodes of AD in the infants of mothers who received any of the probiotic supplements compared to the placebo group; however, there was no difference in skin prick tests among the experimental groups (16).

There is no reliable evidence to date that strongly supports their safe application of probiotics.  In spite of the weak evidence, a considerable number of clinicians prescribe the use of probiotics for the prevention of eczema (18). 

AD is a multi-factor disease that requests personalized approach. The step-wise model with regard to the disease severity provides a practical algorithm to the disease management. Patient and parent therapeutic education represent an important element of the treatment plan. The future of AD treatment belongs to novel biological therapeutic agents coming in the recent years.  

References:

1. Carroll CL, Balkrishnan R, Feldman SR, Fleischer AB, Jr., Manuel JC. The burden of atopic dermatitis: impact on the patient, family, and society. Pediatr Dermatol. 2005;22(3):192-9.
2. Kemp AS. Cost of illness of atopic dermatitis in children: a societal perspective. Pharmacoeconomics. 2003;21(2):105-13.
3. Mancini AJ, Kaulback K, Chamlin SL. The socioeconomic impact of atopic dermatitis in the United States: a systematic review. Pediatr Dermatol. 2008;25(1):1-6.
4. Verboom P, Hakkaart-Van L, Sturkenboom M, De Zeeuw R, Menke H, Rutten F. The cost of atopic dermatitis in the Netherlands: an international comparison. Br J Dermatol. 2002;147(4):716-24.
5. Flohr C. Recent perspectives on the global epidemiology of childhood eczema. Allergol Immunopathol (Madr).39(3):174-82.
6. Arnold RJ, Donnelly A, Altieri L, Wong KS, Sung J. Assessment of outcomes and parental effect on Quality-of-Life endpoints in the management of atopic dermatitis. Manag Care Interface. 2007;20(2):18-23.
7. Lewis-Jones S. Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema. Int J Clin Pract. 2006;60(8):984-92.
8. Meltzer LJ, Moore M. Sleep disruptions in parents of children and adolescents with chronic illnesses: prevalence, causes, and consequences. J Pediatr Psychol. 2008;33(3):279-91.
9. Weisshaar E, Diepgen TL, Bruckner T, Fartasch M, Kupfer J, Lob-Corzilius T, et al. Itch intensity evaluated in the German Atopic Dermatitis Intervention Study (GADIS): correlations with quality of life, coping behaviour and SCORAD severity in 823 children. Acta Derm Venereol. 2008;88(3):234-9.
10. Wuthrich B. Clinical aspects, epidemiology, and prognosis of atopic dermatitis. Ann Allergy Asthma Immunol. 1999;83(5):464-70.
11. Garmhausen D, Hagemann T, Bieber T, Dimitriou I, Fimmers R, Diepgen T, et al. Characterization of different courses of atopic dermatitis in adolescent and adult patients. Allergy.68(4):498-506.
12. Allen S. J., Jordan S., Storey M., Thornton C. A., Gravenor M. B., Garaiova I., et al. Probiotics in the prevention of eczema: a randomised controlled trial. Arch. Dis. Child. 99. 2014.  1014–1019.
13. Baquerizo Nole KL , Yim E , Keri JE. Probiotics and prebiotics in dermatology. J Am Acad Dermatol. 2014;71 (4):814- 21
14. Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease. 4-year follow-up of a randomized placebo-controlled trial. Lancet 2003;361:1869e71.
15. Kalliomaki M, Salminen S, Poussa T, Isolauri E. Probiotics during the first 7 years of life: a cumulative risk reduction of eczema in a randomized, placebo-controlled trial. J Allergy Clin Immunol 2007;119:101
16. Lee J, Seto D, Bielory L. Meta-analysis of clinical trials of probiotics for prevention and treatment of pediatric atopic dermatitis. J Allergy Clin Immunol 2008;121:116
17. Barclay L. Benefits of probiotics reviewed. Am Fam Physician 2008;78:107
18. Rather IA, Bajpai VK, Kumar S, Lim J, Paek WK, Park Y-H. Probiotics and Atopic Dermatitis: An Overview. Frontiers in Microbiology. 2016;7:507

Denica Zheleva
Tokuda Hospital Sofia
Dermatologic Clinic Sofia
Sofia, Bulgaria

Back to Question & Answer list