Atopic dermatitis (AD) is a chronic, recurring disease of the skin, associated with abnormal barrier function of the skin, immunologic sensitization, and other mechanisms.1

The general prevalence of this disease has increased between 2-fold and 3-fold in recent decades. The disease manifests during the 1st year of life in approximately 60% of cases but may appear at any age. Its course may be continuous for long periods or may be recurrent. AD is mild in approximately 80% of children affected2.

Probiotics are defined by the WHO as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host”3.

Multiple mechanisms have been proposed for how probiotics reduce atopy, including shifting the Th1/Th2 balance toward Th1 by inhibiting Th2 cytokines or increasing production of regulatory cytokines such as IL-10 through maturation of dendritic cells or their receptors4.

The objective of this study is to perform a systematic review and meta-analysis to determine whether oral administration of probiotics reduces the severity of atopic dermatitis based on the Scoring Atopic Dermatitis (SCORAD) scale in patients under 18 years of age with an established diagnosis of AD.

We performed a systematic review that included randomized clinical trials published to 2020. The studies had to compare the effect of probiotics with a placebo in reducing the severity of atopic dermatitis. The study population was patients under 18 years of age with an established diagnosis of atopic dermatitis, the severity of which was measured using the SCORAD scale.

Studies that did not meet the inclusion criteria, inconclusive studies, those that presented conflicts of interest, narrative reviews, studies with results other than those sought, studies carried out on animals, studies with interventions other than the clinical interest of this study, and those with a population over 18 year of age were excluded.

The search was performed in the following databases: MEDLINE, Web Of Science (WOS), Scopus, ClinicalTrials.gov, Epistemonikos, Trip medical database, and Biblioteca virtual in salud (BVS). The search string was as follows: (((«Dermatitis, Atopic»[Majr]) AND «Probiotics»[Majr])) AND (((«Child»[Mesh]) OR «Child, Preschool»[Mesh]) OR «Adolescent»[Mesh]).

A total of 2566 articles were found and after eliminating duplicates, we obtained 2412 articles, of which, when the inclusion criteria were applied, 29 articles were obtained, and 2392 records were excluded. The authors MFT and AFPL evaluated the 29 articles based on their level of evidence and discarded 9: 2 were excluded because they did not meet the inclusion criteria, 6 did not specify important data, and 1 did not include the necessary statistical results. Finally, 20 studies were included in the systematic review and 17 studies in the meta-analysis (Fig. 1).

Figure 1.

Flow chart of results.

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Risk-of-Bias Assessment

The risk of selection, performance, detection, attrition, and notification bias was analyzed for each study based on the criteria proposed by the Cochrane Handbook for Systematic Reviews of Interventions. This analysis can be seen in Figs. 2 and 3, which show the individual risks of bias based on the criteria of both researchers.

Figure 2.

Risk-of-bias assessment: review based on the judgement of the authors of the risk of bias, presented as a percentage of all the articles included.

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Figure 3.

Risk-of-bias assessment: review based on the judgement of the authors of the risk of each one of the articles included.

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Twenty studies included in the systematic review were analyzed (Table 1), of which 16 supported the use of probiotics to reduce the SCORAD severity in atopic dermatitis. With regard to the type of probiotic, 7 studies used combinations of strains and 13 used single strains; the most commonly used genus was Lactobacillus, species rhamnosus. The frequency of administration of the probiotic varied from 1 to 2 times per day and duration of treatment in the studies varied between 4 and 12 weeks.

The meta-analysis included 17 studies and the global result found a difference in measurement of –0.38, with a 95% CI of –0.63 to –0.14, in favor of the use of probiotics; however, high heterogeneity was found in the studies due to clinical and methodological variability, with I2 = 76% and χ2 with P = .00001 (Fig. 4).

Figure 4.

Forest plot: efficacy of probiotics vs. placebo in reducing the severity of AD measured by SCORAD.

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Subgroup analyses were performed according to type of strain (Fig. 5) and follow-up time (Fig. 6) for the use of probiotics to reduce the SCORAD; nevertheless, high heterogeneity was found in both analyses. With regard to the strain, greater benefit was not found with the use of Lactobacillus rhamnosus in comparison with the other probiotic strains. Based on the time of administration, a greater benefit was found after administration of probiotics for 12 weeks.

Figure 5.

Forest plot: efficacy of Lactobacillus rhamnosus and other probiotics vs. placebo in reducing the severity of AD measured by SCORAD.

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Figure 6.

Forest plot: efficacy of probiotics vs. placebo in reducing the severity of AD by follow-up time.

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Analysis of Sensitivity and Reporting Bias

A sensitivity analysis was performed, and no variations were found after repeatedly reviewing the data, and the results suggested no important changes. Reporting bias was assessed using a funnel plot (Fig. 7) and was corroborated using the trim-and-fill method24, where a symmetric distribution of the studies can be observed, approaching a funnel shape, which makes it possible to rule out publication bias.

Figure 7.

Funnel plot: use of probiotics vs. placebo to reduce the SCORAD score.

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The results of this systematic review indicated that probiotics have a beneficial effect in pediatric patients with atopic dermatitis.

These results are supported by the results obtained in the meta-analysis, in which the global results support the use of probiotics to reduce the SCORAD. The heterogeneity of the studies, however, does not make it possible to determine the real magnitude of the degree to which the probiotics reduce the severity of AD as measured by SCORAD.

This heterogeneity is due to the different interventions in each study, resulting from the use of different strains, the doses of probiotics, different duration of the treatments, and the subjectivity of the SCORAD scale for evaluating the severity of the AD.

Given the heterogeneity of the characteristics of the populations between the different studies, the analysis by subgroups does not show potentially real results, except for follow-up, in which case it was established that the efficacy of the use of probiotics is observed following administration for more than 12 weeks.

Makrgeorgou et al25 performed an update of a systematic review similar to ours, based on a previous review carried out in 2017. That review included 39 articles that, although they provided a significant sample, did not specifically analyze the pediatric population and included the use of symbiotics. The study concluded that probiotics reduce SCORAD severity but with a very low score for determining a significant change in the symptoms of atopic dermatitis.

The systematic review carried out by Huang et al26 found that more evidence was required to recommend probiotics in a generalized manner. This is because the articles included covered small and heterogeneous populations, which reduced the power of evidence of the review, unlike this review, which includes a larger number of studies and with larger populations.

The limitations of this systematic review include the use of different strains of probiotic, which may lead to different results and individual conclusions in each study. Moreover, several major differences exist between the participants in the clinical trials: in some, it was established that the participants should follow a strict diet with no fermented foods, restriction of the use of antibiotics, and other requirements that were not present in all the clinical trials.

In the statistical analysis for the meta-analysis, heterogeneity was found between the populations of the different studies. This constituted a limitation when analyzing the results, as it made it impossible to determine the reduction in the SCORAD score expected in patients with AD following administration of the probiotic. Another limiting factor involves the association of pharmaceutical companies and food manufacturers in the manufacture of probiotics for the trials, which may be a potential source of conflicts of interest.

The use of probiotics has been studied for several years, with a particular focus on diseases linked to the digestive system. Given that a wide range of probiotics exists on the market in our country, we may begin to use them as coadjuvant treatment in AD.

Oral probiotics, especially strains of bacteria of the genus Lactobacillus, are useful for reducing the severity of atopic dermatitis but more homogeneous studies are required to determine the magnitude of this benefit.

The authors declare that they have no conflicts of interest.