Probiotics and Skin
8.3 Eczema
8.3.1 Probiotics for Treating Eczema
Probiotic bacteria have been quite widely investigated for effects on the treatment of eczema with or without associated food allergy, in infants and children. Most of the studies involving eczema have evaluated Lactobacillus species either alone or in combination with other probiotic bacteria. Early studies in small numbers of infants and children reported improvement in eczema (SCORAD or symptoms) following treatment with Lactobacillus rhamnosus GG (LGG), Bifidobacterium lactis Bb-12,
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or B. breve M-16 V. In two of these studies, probiotic treatment resulted in more rapid alleviation of the eczema than with placebo: SCORAD improved significantly in the probiotic treatment groups but not the placebo groups at early time points;
however, by the 2- to 6-month follow-up the eczema was markedly diminished in both treatment groups, with similar SCORAD scores in the treatment and placebo groups (Isolauri et al. 2000; Majamaa and Isolauri 1997). A larger study of L. fermentum VR1-003PCC in children with eczema also demonstrated improvements in eczema severity and extent in probiotic-treated infants but not in placebo-treated infants.
However, SCORAD, parental perception of eczema, the impact of eczema on the family, and topical corticosteroid use were not significantly different between the active and placebo groups (Weston et al. 2005).
In contrast to these studies, many others have failed to confirm a beneficial effect of probiotics for the treatment of eczema (Brouwer et al. 2006; Folster-Holst et al.
2006; Gruber et al. 2007; Rosenfeldt et al. 2003; Sistek et al. 2006; Viljanen et al.
2005a). A small crossover study assessing the efficacy of a probiotic yoghurt con- taining L. paracasei Lpc-37, B. lactis 420, and L. acidophilus 74–2 in 15 adults with atopic dermatitis reported a trend toward reduced SCORAD with probiotic treat- ment (15.5 point reduction); however, this effect did not reach statistical signifi- cance (P = 0.081) (Roessler et al. 2008). Interestingly, in two studies showing no overall effect, subgroup analyses revealed improvements in SCORAD following treatment with LGG (Viljanen et al. 2005a) or the combination of L. rhamnosus HN001 and B. lactis HN019 (Sistek et al. 2006) for a subgroup of children with immunoglobulin E (IgE)-associated (“atopic”) eczema (Sistek et al. 2006; Viljanen et al. 2005a). Probiotic treatment was associated with low-grade inflammation, as evidenced by moderate increases in C-reactive protein (CRP) and interleukin-6 (IL-6), which the authors suggested may suppress inflammation by inhibiting production of other inflammatory factors and inducing a regulatory immune response (Viljanen et al. 2005b). There is no direct evidence, however, that probiotics induce regulatory immune responses or inhibit inflammatory responses when used to treat individuals with established eczema.
Our recent systematic review evaluating the use of probiotics for treating eczema (Boyle et al. 2008) concluded that probiotics do not appear to be an effective treat- ment, and there is insufficient evidence to support their use for this condition. Our Cochrane systematic review (Boyle et al. 2008) included 12 studies (summarized in Table 8.1) but not the recent study in adults by Roessler et al. (2008). We found no significant reduction in eczema symptoms with probiotic treatment compared with placebo—mean difference 0.90 points on a 20-point visual analogue scale with the 95% confidence interval (CI) at −1.04 to 2.84 —and no significant difference in investigator-rated eczema severity between probiotic and placebo treatments (Fig. 8.1) (Boyle et al. 2008). Subgroup analysis by age, eczema severity, presence of atopy, or presence of food allergy did not identify a population with different treatment outcomes (Boyle et al. 2008). Significant heterogeneity was noted between studies, and we found evidence that it may be explained by the use of different probiotic strains. Therefore, lack of effect based on pooled data from different pro- biotics does not exclude the possibility that a certain strain or strain combination
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Table 8.1Randomized controlled trials of probiotic ± prebiotic supplementation for the treatment of eczema StudyMethodsParticipantsInterventionsOutcomes Brouwer 2006 (Brouwer et al. 2006) 3 month parallel group RCT50 formula fed infants with eczema and suspected CMATest: eHF with L. rhamnosus or LGG at 5 × 109 cfu/100 mlSCORAD Control: eHF without probiotic Folster-Holst 2006 (Folster-Holst et al. 2006)
8 week parallel group RCT53 children with eczemaTest: 1 × 1010 cfu/day LGGGlobal assessment; QoL score; SCORAD; Medication useControl: microcrystalline cellulose Gruber 2007 (Gruber et al. 2007)12 week parallel group RCT106 infants with eczemaTest: 1 × 1010 cfu/day LGGSCORAD SCORAD 15–40Control: placebo capsuleMedication use Hattori 2003 (Hattori et al. 2003)3 month parallel group RCT17 children with eczema, suspected CMA, low fecal Bifidobacterium level
Test: eHF with prebiotic and B. breve M16-V at 5–15 × 109 cfu/day.Eczema severity scoring scale Control: eHF with prebiotic and no probiotic Isolauri 2000 (Isolauri et al. 2000)Parallel group RCT ?duration27 breast fed infants with eczemaTest: eHF with Bb-12 at 1 × 109 cfu/g or LGG at 3 × 108 cfu/gSCORAD Control: eHF without probiotic Kirjavainen 2003 (Folster-Holst et al. 2006)
Parallel group RCT ?duration27 infants with eczema and suspected CMATest: eHF with LGG at 3 × 1010 cfu/kg/ daySCORAD Control: eHF without probiotic Majamaa 1997 (Alfaleh and Bassler 2008) 1 month parallel group RCT31 children with eczema and suspected CMATest: eHF with LGG at 5 × 108 cfu/gSCORAD Control: eHF without probiotic Passeron 2006 (Passeron et al. 2006)
3 month parallel group RCT48 children with eczemaTest: prebiotic powder with L. rhamnosus Lcr35 at 3.6 × 109 cfu/day Global assessment SCORAD > 14Control: prebiotic powder aloneSCORAD
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StudyMethodsParticipantsInterventionsOutcomes Rosenfeldt 2003 (Gueimonde et al. 2006) 6 week cross-over RCT58 children with eczemaTest: L. rhamnosus 19070–2 and L. reuteri DSM12246 at 2 × 1010 cfu/ day
Global assessment Control: skim milk powder + dextroseMedication use SCORAD Sistek 2006 (Sistek et al. 2006)12 week parallel group RCT60 children with eczema, atopy, SCORAD > 10Test: L. rhamnosus and B. lactis at 2 × 1010 cfu/daySCORAD Control: microcrystalline cellulose Viljanen 2005 (Viljanen et al. 2005a)
4 week parallel group RCT252 infants with eczema and suspected CMATest: cow’s milk elimination, eHF and LGG at 1010 cfu/day or probiotic mix
SCORAD Control: cow’s milk elimination and eHF Weston 2005 (Weston et al. 2005)8 week parallel group RCT56 children with eczemaTest: L. fermentum VR1-003PCC 2 × 109 cfu/dayGlobal assessment; QoL score; SCORAD; Medication useModified SCORAD ³ 25Control: maltodextrin placebo Modified from Boyle et al. (2008) RCT randomized controlled trial, CMA cow’s milk allergy, eHF extensively hydrolyzed formula, LGG Lactobacillus rhamnosus GG, CFU colony-forming units, SCORAD Scoring Atopic Dermatitis, QoL quality of life
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could still be effective. In contrast to our meta-analysis, a recent meta-analysis by Michail et al. reported a significant difference favoring probiotics in reducing the SCORAD score of children with eczema (mean change from baseline was −3.01 with the 95% CI −5.36 to −0.66, P = 0.01), and children with moderately severe disease were more likely to benefit (Michail et al. 2008). The authors of the latter meta-analysis were able to acquire original data from a greater number of included trials, which may account for the different conclusions of the two studies. However, the clinical significance of a three-point reduction in SCORAD score is unclear and compares poorly with the treatment effect seen with established eczema treatments.
Topical application of probiotics for the treatment of eczema was recently evaluated in a single study that reported a significantly reduced SCORAD score and pruritus following treatment with topical Vitreoscilla filiformis lysate cream versus placebo and decreased loss of sleep compared to the start of treatment (Gueniche et al.
2008). The treatment was also associated with reduced Staphylococcus aureus colo- nization of skin. Future studies evaluating topical probiotics for the management of eczema will be of great interest.