Treatment Challenges in Atopic Dermatitis: Is probiotic the way to go? Saturday, 7 May 2016 Park Royal, Beach Road, Singapore

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Speaker  1

Treatment of Atopic Dermatitis in the GP Setting

Dr Tan Kian Teo, MB BCh, MRCP (UK), FAMS (Dermatology)

Atopic dermatitis is a common skin condition. It frequently affects the neck, front of elbows and behind the knees. In very young children, it commonly affects the face and outer surfaces of the arms and legs. It may be associated with asthma and allergic rhinitis. Most patients with atopic dermatitis also have very dry skin.

The incidence of atopic dermatitis is increasing. A study by Tay and colleagues published in the British Journal of Dermatology in 2002 found that 1 in 5 school-going children in Singapore suffered from atopic dermatitis.

Pathogenesis and clinical features

The cause of atopic dermatitis is multi-factorial. Impaired skin barrier function, house dust mite (HDM) allergy, staphylococcus aureus infection, use of alkaline soaps, food allergy, low environmental humidity, and psychological stress may all contribute to the pathogenesis.

It has also been reported that the loss-of-function (null) mutation within the filaggrin (FLG) gene is a strong risk factor for atopic dermatitis (AD). A study by Cai and colleagues hypothesised that the absence or reduction of the filaggrin protein could compromise skin barrier and increase patients’ susceptibility to recurrent skin infection. The study, which included 228 Singaporean Chinese patients, highlighted a novel association between FLG-null mutations and an increased susceptibility to recurrent bacterial skin infection among patients with AD.

Food allergy may play a role in very young children with atopic dermatitis. The common allergens are cow’s milk, egg white and peanuts. A skin prick test may be done in cases where food allergy is suspected. A radioallergosorbent (RAST) test and food challenge can also help in determining if children are allergic to certain types of food.

Treatment options

It is recommended patients with atopic dermatitis bathes or showers not more than once or twice daily. Non-soap, hypoallergenic, fragrance-free cleansers with neutral to low pH are recommended. Moisturizers should be liberally and frequently applied.

The mainstay of treatment for atopic dermatitis is topical corticosteroids. Antihistamines, antimicrobials, topical calcineurin inhibitors (TCIs), and systemic anti-inflammatory agents can also be used when needed. Proactive therapy with regular intermittent application of topical corticosteroids or calcineurin inhibitors is advocated in patients with frequent flares. It has been found that proactive treatment can prevent the flare-ups.

Adjunctive treatments, which include double pyjama method, wet dressings, and phototherapy can also be considered.

In the near future, biologics, phophodiesterase-4 inhibitor and janus kinase (JAK) inhibitor may become available in the treatment of atopic dermatitis.

 

Speaker 2speakers

Clinical Evidence of Probiotic for Atopic Dermatitis

Dr Priya Sen, BSc (Hons), MBBS, FRCP (UK), Dip GUM (UK), FAMS (Singapore)

Prevalence of Atopic Dermatitis

The increasing prevalence of allergic diseases like atopic dermatitis (AD) in children in industrialised countries can be attributed to the “exaggerated hygiene” in early childhood typical of western lifestyle. According to the revised hygiene hypothesis, this increase is caused by a changed intestinal colonisation pattern during infancy, which has an impact on the immune system. It added that the insufficient microbial exposure in this phase appears to promote the development of allergies. Thus, the need to search for more novel ways to treat and prevent atopic dermatitis.

Definition of Terminologies and Uses

Prebiotics are defined as non-digestable carbohydrates that act as food for probiotics, which are live microorganisms offering health benefits to the host when administered in adequate amounts. Synbiotics meanwhile is the combination of prebiotics and probiotics.

Probiotics can act as a supplement with medical benefits. They have been used to treat diarrhoea especially following treatment with certain antibiotics, prevent and treat vaginal yeast infections and urinary tract infections,  treat irritable bowel syndrome, speed up the treatment of certain intestinal infections, and prevent or reduce the severity of colds and flu.

These friendly probiotic strains are identified as L. acidophilus, which supports nutrient absorption and helps with the digestion of dairy foods; B. longum, which acts as a scavenger of toxins; and B. bifidum, which is critical for the healthy digestion of dairy products and breaking down of complex carbohydrates, fat, and protein into small components that the body can use more efficiently.

There is also L. fermentum which helps neutralise some of the byproducts of digestion and promote a healthy level of gut bacteria. L. rhamnosus on the other hand can help prevent the occasional traveller’s diarrhoea.

Simply put, probiotics can help boost the immune system, encourage the production of antibodies especially in babies and children. They can protect kids from allergies later in life.

Dual Coating Technology

While the consumption of probiotics is highly recommended, not all products available in the market can ensure the survival rate of these friendly bacteria during the process of production and delivery into the intestine. Proper “coating” of probiotics is essential. Without it, a large portion of the ingested bacteria will die due to gastric acid and bile salts in the gastrointestinal tract.

To solve the problem, Cell Biotech developed a new dual-coating lactic acid bacteria (LAB) known as Duolac. The patented technology is the fourth generation of probiotics. The first generation was non-coated, the second was enteric-coated, and the third was micro-capsulated.

Dual coating protects the LAB throughout ingestion and delivers LAB safely to intestines so that they can colonise and proliferate in the intestines. It guarantees stability during manufacture and shelf life of the product, keeping a large portion of the LAB alive. Also, high bacterial counts reaching the intestines are important for probiotic colonisation and effect.

Duolac Derma in AD patients

In 2006, a group of experts investigated the therapeutic effects of Duolac Derma on adolescent  and adult atopic dermatitis (AD) patients. The open-label study, published  in the Journal of Microbiology and Biotechnology, had 50 subjects of either sex, aged more than 2 years with mild to moderate AD, classified according to the severity criteria developed by Rajka and Langeland. These patients were given a controlled dosage of the product and evaluated within an 8-week period.

The results included an improvement of  eczema area and severity index (EASI) score, eczema in 50% of the patients, and pruritus. The effect was more pronounced for the patients with very high IgE levels (>1,000 ku/l) and for the patients with moderate disease severity.

There was no significant difference in the therapeutic effects between the childhood AD and adolescent and adult AD patients. Similarly, there were no significant changes in cytokine levels as well as the total IgE and ECP levels, in the patients’ serum. Treatment with the mixture of the four probiotic strains was generally well tolerated. The mixture of four probiotic strains has been found beneficial for the management of the adolescent and adult AD patients, as well as for the childhood AD patients.

Other Studies Providing Clinical Evidence

A 2012 study on the effects of probiotics on the treatment of children with AD published in the Annals of Dermatology suggested that  probiotics are effective in the pathogenesis of AD through their effects such as: restoring the mucosal barrier function in the intestines, degrading food antigens, regulating the intestinal microbial composition and activities, and stimulating the production of secretory IgA. They also block Th2 allergic response by stimulating the Th1 response. Probiotics regulate local and systemic immunity and thus alleviate the severity of clinical symptoms.

However, other investigations published in the Journal of the American Academy of Dermatology in 2014 concluded that there is still limited evidence to support the use of probiotics  as treatment especially for established AD. Thus, pro-/ prebiotics cannot be recommended at this time.

The American Journal of Clinical Dermatology published a study on probiotics for the treatment or prevention of atopic dermatitis based on randomised controlled trials in 2008. Following mixed results, experts concluded that more randomised controlled trials (RCTs) need to be conducted “to elucidate whether probiotics are useful for the treatment or prevention of AD.”

Speaker 3107

Microbiological Approach to Probiotic Development and Application

Dr Myung-Jun Chung, Adjunct Professor, Department of System Biology, Yonsei University, South Korea

The Importance of Dual Coating

Experts cannot stress enough the importance of the delivery of high bacterial counts to the intestines. This allows the probiotics to colonise and exert their effects. However, their survival is challenged by factors such as the manufacturing process of probiotics, presence of digestive enzymes in the mouth, low pH in the stomach, bile secretion in the duodenum and spicy foods. Thus, it is vital for a coating system to protect the bacteria as they make their journey through the intestines.

Cell Biotech has developed a patented dual coating technology that ensures safe delivery of the bacteria to the gut. The dual coated probiotic, called Duolac, has two coating layers. The first coating is made up of a protein and peptide matrix that protects the lactic acid bacteria (LAB) against gastric acid and bile salts. This allows the live LAB to be safely delivered to the intestines where they colonise and proliferate. The second coating is made up of a hydro colloidal polysaccharide matrix that protects the bacteria against moisture, heat and mechanical pressure during manufacture, distribution and storage. The dual coating starts to dissolve at pH 6.0 and LAB begin to be released. The dual coating is completely dissolved as the LAB are fully released at pH 7.0. The liberated bacteria will start to colonise and proliferate in the intestine.

Product Performance

Cell Biotech’s product performance is proven by key microbiological studies including the strain mix, full genome sequencing, and documentation from clinical studies.

The strain mix adapts a 3-genus-technique which ensures a strong efficacy in Duolac products. This method exploits the growth synergies between three different probiotic genuses that complement each other.

The growth rate of each strain is the most important key factor to make an optimum strain cocktail. Based on the data of growth rate and the different regions of the intestine, an optimum strain cocktail can be made. This is based on three types of growth rates: high growth rate bacteria (in small concentration), low growth rate bacteria (in high concentration), and medium growth rate bacteria (in medium concentration).

Clinical studies have documented that the 3-genus-technique is effective in providing synergistic effects for the bacterial strains.

Cell Biotech has based its products on 56 research reports related to probiotics. Most importantly, these studies on Duolac technology revealed that the survival rate for the bacteria is a hundred times higher compared to the non-coated ones.

With reference to these documents, Duolac Daily Vitality serves as a good treatment for irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), and constipation. On the other hand, Duolac Derma can help treat those with atopic dermatitis.

To further test the safety and effectiveness of these strains, another study was conducted to evaluate the influence of various spices and propolis on probiotics isolated from Koreans. The results showed that most Korean probiotic strains were resistant to all spices and propolis tested.

Also, the growth rates of some Korean probiotic strains (Bifidobacterium lactis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophileus) were even increased by specific spices or propolis. However, the survival rates of most European probiotic strains were reduced by various spices or propolis, and the growth rates of a few European probiotic strains (Lactobacillus. helveticus, Streptococcus. thermophilues) were greatly decreased in the presence of specific spices. In summary, the strains are strong enough to withstand even the spiciest food.

Most of Cell Biotech’s strains are derived from healthy people and fermented food such as kimchi. Furthermore, the strains have been optimised for rapid growth after consumption.

In a study by Yuen and colleagues on the effect of a double-coated probiotic formulation on functional constipation, the fecal analysis revealed that the levels of bacterial species consumed in the dual coated group were about 100-fold or greater than those in the non-coated group.

Meanwhile, a full genome sequencing by Duolac has proven exact strain identification, enzyme production in the digestive system, vitamins synthesis, among others. Safety has been guaranteed as well.

The genome sequencing of Cell Biotech’s strains has shown that all of Cell Biotech’s 4 Bifidobacterium species contain genome that can synthesise Vitamin B group. These four strains are potentially very helpful in the growth of infants and children.

According to previously published studies, efficient utilisation of Human Milk Oligosaccharides (HMOs) is critically important for babies’ health. Cell Biotech’s strains are found to possess various genes encoding beneficial enzymes responsible for degradation of oligosaccharides (also found in mushroom, nut, and seaweed).

Worldwide Distribution

Today, Cell Biotech’s Duolac products are being distributed in 44 countries. In the last 10 years, they have been proven safe and effective for different nationalities with unique eating habits and cultures. Cell Biotech has indeed developed into a global company specialising in probiotics based on product safety, superior technology, and various certifications and patents acquired at home and abroad.

References:

• Tay YK, Kong KH, Khoo L, et al. The prevalence and descriptive epidemiology of atopic dermatitis in Singapore school children. Br J Dermatol. 2002; 146(1): 101-106.

• Williams HC, Burney PG, Hay RJ, et al. The U.K. Working Party’s Diagnostic Criteria for Atopic Dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis. Br J Dermatol. 1994;131:383–396.

• Cai CS, Chen H, Koh WP et al. Filaggrin Mutations are Associated with Recurrent Skin Infection in Singaporean Chinese Patients with Atopic Dermatitis. Br J Dermatol. 2012;166(1):200-203

• Danby SG, Al-Enezi T, Sultan A, et al. The effect of aqueous cream BP on the skin barrier in volunteers with a previous history of atopic dermatitis. Academic Unit of Dermatology Research Department of Infection and Immunity, Faculty of Medicine, Dentistry and Health, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, U.K.

• Chiang C, Eichenfield LF. Quantitative assessment of combination bathing and moisturizing regimens on skin hydration in atopic dermatitis. Department of Dermatology, University of California San Francisco Medical Center, San Francisco, California, Department of Pediatrics and Medicine (Dermatology), University of California, San Diego School of Medicine, San Diego California, Pediatric and Adolescent Dermatology, Rady Children’s Hospital, San Diego, San Diego, California

• Hajar T, Leshem YA, Hanifin JM, et al. A systematic review of topical corticosteroid withdrawal (“steroid addiction”) in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol. 2015; 72(3): 541-549.

• Thaci D, Reitamo S, Gonzalez MA, et al. for the European Tacrolimus Ointment Study Group. Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study. Br J Dermatol. 2008;159(6): 1348–1356.

• Yeşilova Y, Çalka Ö, Akdeniz N, et al. Effect of Probiotics on the Treatment of Children with Atopic Dermatitis. Ann Dermatol. 2012; 24(2): 189–193.

• Betsi GI, Papadavid E, Falagas ME. Probiotics for the treatment or prevention of atopic dermatitis: a review of the evidence from randomized controlled trials. Am J Clin Dermatol. 2008;9(2):93-103.

• Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis. J Am Acad Dermatol. 2014;71:1218-1233.

• Yeun Y1, Lee J. Effect of a double-coated probiotic formulation on functional constipation in the elderly: a randomized, double blind, controlled study. Arch Pharm Res. 2015;38(7):1345-1350.

• Yim, JH, Kim DH, Ku JK, et al. Therapeutic Effects of Probiotics in Patients with Atopic Dermatitis. J Microbiol Biotechnol. 2006;16(11),:1699–1705.

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