Topical probiotic L. lactis treatment in atopic dermatitis - A double-blinded, placebo-controlled pilot studyTo the Editor,Changes in the skin microbiome have been identified as major pathogenetic components in atopic dermatitis (AD). Probiotics have been studied as potential therapeutic agents to maintain normal cutaneous microbiome and prevent colonization with pathogens.1We aimed to compare the efficacy of probiotic Lactococcus lactislysate cream in different concentrations in AD.We conducted a prospective, double-blinded, randomized, placebo-controlled, split-body clinical interventional study. 13 patients were enrolled and randomly assigned to one of four groups with different concentrations of probiotic lysate cream including placebo (Supplement Table S1).Patient’s skin was investigated 3 times, at baseline, after 4 weeks of treatment and after 4 weeks of follow-up. During each visit, the skin was evaluated, and AD severity was characterized with investigator-dependent methods and patient-reported questionnaires. Online Supplement presents detailed information about the study setting and patient characteristics.There were no clear differences between the treatment groups regarding disease severity (EASI, IGA), TEWL or parameters associated with QoL (pruritus and sleep disturbance VAS, DLQI, POEM, ADCT). Mean changes in disease severity (EASI local and total), TEWL and QoL indicators (DLQI and POEM) are shown in Fig. 1.Mean local EASI (eczema site) baseline values were 3.00, 1.47 and 1.05 in the 3%, 10% and 30% probiotic lysate groups respectively, and 4.93 in the placebo group. After 4 weeks of treatment, local EASI values were 3.20, 1.20 and 0.80 in the probiotic lysate groups and 4.53 in the placebo group, with no significant decrease compared to baseline (p=0.76). Total EASI values showed similar results (p=0.31) and there were also no differences between local EASI and total EASI. IGA values were similar (p=0.61) (Table 1).QoL associated parameters did not change significantly during the study and were similar in all patient groups (Supplement Table S2). Mean DLQI was 9.33, 7.00 and 8.00 in the probiotic lysate groups and 10.67 in the placebo group. At 4 weeks the values were comparable, 9.00, 8.00 and 10.33 in the probiotic lysate groups and 7.67 in the placebo group, with no significant differences (p=0.76). POEM and ADCT showed no significant differences (p=0.76 and p=0.72, respectively). Complete study results, clinical data, eosinophil counts, total serum IgEs and specific IgEs to aeroallergens at baseline are presented in the Supplement (Table S3).While enteral probiotics have been studied in detail, the role of topical probiotics in AD remains uncertain. Several studies have investigated the use of probiotics in creams with living or dead bacteria or bacterial lysates with inconsistent results.2,3 Further evidence is needed to determine efficacy, dosing, and specific bacterial strains. Most of the previous studies observed positive effects, which is contrary to our findings.4In addition to ameliorating disease severity, in vitro studies have shown that probiotics suppress cutaneous inflammation and Th2-responses through immunomodulatory mechanisms.5 We did not measure inflammatory parameters in our patients. However, to our knowledge, our study is the first in vivo study in humans investigating Lactococci in the treatment of AD.Most probiotic preparations are considered relatively safe and are classified as commercial food supplements. We did not observe relevant adverse effects and the used probiotic L. lactis lysate cream was well tolerated.Important study limitations were small and heterogenous patient groups, relatively short follow-up time and no long-term evaluation.We observed no clear differences between the treatment groups of probiotic L. lactis lysate cream and placebo. Further research is needed to investigate the role of topical probiotics in AD. It would be interesting to investigate anti-inflammatory effects in larger patient cohorts.6Table 1: Severity of atopic dermatitis and TEWL values, results of follow-up and comparisons