A closer look at atopic dermatitis secondary infections

Atopic dermatitis (AD) is a common chronic inflammatory skin disease which often complicated with secondary infections.

 
The skin lesions of most patients suffering from AD and eczemas are colonized with Staphylococcus/aureus, the main pathogen in AD. A correlation between the severity of the eczema and colonization with S. aureus has been demonstrated.Therefore, we had developed a product for the management of AD secondary infections, based on a unique mechanism of action of stimulating human beta-defensin-3 (hBD-3) – an anti-microbial peptide that functions as a natural antibiotic in human skin.


Anti-microbial peptides (AMPs) function as anti-microbial and anti-inflammatory barriers. There are several families of AMPs in human skin such as Defensin, Cathelicidins and Psoriasin. We had focused in our research on human beta-defensin-3 (hBD-3), a small peptide produced by keratinocytes, since it has a broad spectrum of antimicrobial activities against bacteria, fungi and viruses .1


hBD3 expression is generally low in healthy epithelium but elevated in infected wounds. However, AD lesions demonstrated deficiently low expression of hBD-3, even after infection with S. aureus. The reduced expression of hBD-3 is partly due to the excessive production of TH2 cytokines, IL-4 and IL-13, characterized AD. The low expression of - defensins in AD contributes to an enhanced susceptibility of AD patients to skin infections (mainly by S. aureus) 2,3


Of the 500 Chinese herbal extracts screened in this study for the stimulation of hBD-3 and the inhibition of IL-13 secretion (defensin inhibitor), only two extracts exhibited strong biological activity: Di Yu (Sanguisorba officinalis) and Chun Pi (Ailanthus altissima). These two extracts were also found to have synergistic activity. We therefore decided to use both extracts in the final product formulation. Di Yu is well known in traditional Chinese medicine as an eczema treatment. By contrast, there is no record of Chun Pi relating to the current application.

  

Extraction methods for both plants were optimized by utilizing macro-porous resin chromatography. Based on literature and research, active ingredients were identified in each of the two herbal extracts described above, enabling their use also as biomarkers for standardization. HPLC methods were established for measuring the biomarkers’ concentration in each of these herbal extracts. Purification through adsorptive macro-porous resin is based on differences in molecular weight, polarity, or shape of different molecules in the solution. The resin chromatography resulted in a reduced concentration of impurities and high levels of active ingredients which facilitate enhanced biological efficacy. Indeed, in-vitro studies have shown elevated biological activity of both extracts following the extract optimization process.


Based on in-vitro testing, Bonatics has developed, a topical skin care – Body Cream Forte, part of the Dry Skin product line, containing extracts of Di Yu (Sanguisorba officinalis) and Chun Pi (Ailanthus altissima), in addition to the following four herbal extracts: Da Huang (Rheum palmatum), She Chuang Zi (Cnidium monnieri), Huang Qin (Scutellaria baicalensis) and Dipotassium Glycyrrhizinate (produced from Gan Cao - Licorice), which are used to treat immediate AD symptoms such as redness, itchiness and irritation.


Body Cream Forte was tested for safety and efficacy in a clinical trial on 30 AD patients. Following 3 weeks of treatment, a significant improvement was observed in AD symptoms, mainly symptoms related specifically to secondary infections, such as oedema, oozing and excoriation. A controlled, double-blind, multi-center study is being conducted in Israel and in Spain on 60 children with AD. Preliminary results have shown a significant improvement in all measures of AD symptoms, and a clear superiority of the Body Cream Forte product over Aquosom control .

 

AD secondary infection is most commonly treated by antibiotics. However, the wide-spread use of antibiotics has led to the development of multi-resistant bacterial strains. Furthermore, the use of antibiotics in early life has been shown to cause a disruption in the delicate balance of skin microflora, and, therefore, increases the risk of allergic diseases4.

 

Topical treatment containing herbal extracts that stimulate hBD3 is a new and innovative approach to the prevention and treatment of secondary infections in AD. The treatment enables long-term use and is unaffected by classic antibiotic resistance.

 

This study combines the TCM approach with scientific research, while the product helps the skin prompt innate protection mechanisms against infections, rather than using antibiotics that kill the bacteria.

  

Sharon Rozenblat, PhD
CSO, Kamedis Ltd.
sharon@kamedis.com

 


 

1.Harder J, Bartels J, Christophers E, Schroder JM. Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem. 2001 Feb 23;276(8):5707-13. Epub 2000 Nov 20.

2.Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003 Sep 15;171(6):3262-9.

3.Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, Gallo RL, Leung DY. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002 Oct 10;347(15):1151-60.

4.Torley D, Futamura M, Williams HC, Thomas KS. What's new in atopic eczema? An analysis of systematic reviews published in 2010-11. Clin Exp Dermatol. 2013 Jul;38(5):449-56. Epub 2013 Jun 11. Review.