**7. Conclusion**

376 Atopic Dermatitis – Disease Etiology and Clinical Management

[101]. Land et al recently reported LGG probiotic sepsis occurring in immunocompromised infants and children [102]. A medically fragile infant 6 weeks of age became septic with a strain of LGG that was being provided as a supplement. Molecular DNA fingerprinting confirmed that the LGG probiotic supplement was the bacterial isolate from the infant. Neonatal sepsis and meningitis that were apparently associated with the administration of a probiotic supplement were also reported [103,104]. Children with abnormal immune function, premature infants, and those with indwelling central lines should use these products with caution, because many species such as Lactobacilli, streptococci, and enterococci are potential opportunistic pathogens. Owing to the theoretical risk of immunomodulation, especially in immunocompromised hosts or those with autoimmune

Bifidobacteria have also been consumed in infant formulas for ≥15 years worldwide and have not been associated with any pathologic or adverse event. In particular, studies have documented safety and adequate growth with Bfdbm lactis in infants from birth and in vulnerable populations, including preterm infants, malnourished infants, and infants born to mothers with HIV disease. From the safety point of view, according to current available information, Bifidobacteria, particularly Bfdbm lactis, has a uniquely strong safety profile, making it a good probiotic candidate for newborns and young infants [106]. Lactobacilli, particularly Lctbs rhamnosus (LGG), also seem generally safe and may be a probiotic appropriate for older infants and children [107]. Until adequate data are available for each specific probiotic bacterium, use of probiotics in general cannot be recommended in immunocompromised populations. However, as safety is better documented for specific bacteria, we may be able to use them in certain populations (such as premature infants) that

Another consideration is that cow's milk protein allergy is one of the common food allergies in infants. Culture conditions used in growing several probiotic products may contain cow's milk protein. There have been reports of severe adverse reactions when pediatric patients with cow's milk protein allergy ingested probiotics. Therefore, caution should be used in prescribing such probiotic products in sensitized children to avoid significant reactions. There is also a study worth mentioning by Taylor et al using Lctbs acidophilus daily for the first 6 months of life in newborns of women with allergy. The presence of Lctbs in the body at 6 months of age was associated with increased risk of subsequent cow's milk sensitization as well [87]. Nevertheless other studies have examined the effect of probiotic consumption on sensitization to several allergens (e.g. peanut, hen's egg, soy, wheat, milk, cat, dog), as determined by specific IgE production or skin prick test. The authors could not find a difference before and after the treatment. Interesting another trial by Kopp et al demonstrated that supplementation with LGG during pregnancy and early infancy in affected children it might be associated with an increased rate of recurrent episodes of wheezing bronchitis [88]. However, a recent study was done by Kukkonen et al evaluating airway inflammation in probiotic-treated children at 5 years in 1018 children. Early intervention with probiotics and prebiotics did not affect airway inflammation later in

Furthermore, similarly certain probiotics are known to stimulate Th1 immunity, which has been suggested as one of the mechanisms by which they can suppress Th2-mediated allergic diseases. However, this presumed excessive immunostimulation might aggravate or induce Th1-mediated immune responses and diseases such as type 1 diabetes, multiple sclerosis; and it might cause an additional safety issue [105]. Consequence of over-activation of the

disorders, few reports of probiotic-related disease have been reported [105].

may stand to benefit the most from probiotic use.

childhood [108].

As mentioned above, there is a large amount of conflicting data on the preventive/therapeutic effects of probiotics in AD. Results from metaanalyses and systematic reviews that combine results of studies from different types of probiotics to examine the effects in any disease should be interpreted with caution. One may quickly recognize the degree of heterogeneity among the different probiotic studies. As mentioned, very few studies were similar in design. Several different probiotic strains with different dosing regimens were used, and many studies showed similarity in efficacy to placebo shortly after probiotic therapy was discontinued. Some probiotic studies suggest short-term statistically significant improvement in SCORAD scores and no sustained benefit from continued ingestion. Therefore, subgroup analysis became critical in understanding the outcomes of the studies. Not all children receiving the probiotic agent benefited, but subsets of these patients, mainly those with moderate disease activity and IgE-associated disease (atopic eczema), seemed to have benefited the most. There are also difficulties of recognizing etiology and pathogenesis of AD in which have many mechanisms involved. Similarly, with various strains, especially e.g. in Kopp and Taylor et al's study, development and/or stimulation of Th2-mediated immune responses have been described [87,88]. Additionally, if probiotics are used in patients with ADs for any reason –therapy or prevention- cautionary approach ought to be taken. Thus, probiotics cannot be recommended generally for primary prevention of ADs. Any probiotics should not be used especially in immune-compromised children; even they have at risk for ADs. Finally, there is insufficient but fairly promising evidence to recommend the addition of probiotics to foods for prevention and treatment of AD [111].
