Treating Seborrheic Dermatitis Biofilms

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Do you ever use a dandruff shampoo which works perfectly for a period of time?  And then it just seems to stop working?

It’s quite a frustrating experience.

Procter and Gamble don’t think this phenomenon has anything to do with you building a tolerance to the active ingredient, and is instead a human error of some sort.

I’m not totally convinced.

Over the last couple of decades, research has shown that there are fungal conditions that build a tolerance to antifungal treatments over time.  And the reason for that tolerance is biofilms.

Some of this research branches into Seborrheic Dermatitis.

Whats in this article:

  • What are biofilms?
  • How do they work?
  • How do biofilms affect our skin?
  • How to treat biofilms.
  • References

What Are Biofilms?

Biofilms are complex multicellular systems, in which ‘communities’ of fungi or bacteria thrive under the protection of an extracellular matrix. Biofilms help to explain why skin conditions such as seborrheic dermatitis are difficult to treat with antibiotics and can persist for months to years.

Research is currently being undertaken to find novel strategies for disrupting biofilms, with a range of promising molecules already identified. Up to 80% of common infections are caused by biofilm associated microorganisms, but more development is necessary before promising molecules play a role in clinical practice [1].

How do biofilms work?

Biofilms are complex biological systems, but the idea is relatively simple – that there are evolutionary benefits for microorganisms that grow in communities. These microorganisms adhere to a surface and produce an extracellular matrix – comprising mostly of carbohydrate polymers – physically protecting against external stressors better than individual cell walls [2]:

• Chemical stress (changes in pH, temperature)
• Drug resistance (preventing the penetration of drug molecules)

Interestingly, microorganisms within a biofilm have been shown to share and express unique genes [3]. This poses a significant problem for antibiotic therapy, as resistance can quickly transfer within a biofilm – a colony that is already difficult to treat due to the physical protection of the extracellular matrix.

Biofilms and dermatitis

While substantial research has been conducted into the biological mechanisms of biofilm formation, resistance, and disruption, many of these studies have been with:

• S.mutans – the primary microorganism found in dental plaque
• Candida – identified in dental plaque, as well as in long-term urinary and intravenous catheters known to cause serious blood infections resistant to first-line treatments

These studies cannot reliably be extrapolated because the microorganisms are not commonly associated with chronic skin conditions, and the characteristics of a biofilm depend strongly on the species [13].

Although we are at early stages of research in this area, several studies have attempted to evaluate biofilms in dermatitis skin conditions.

Atopic dermatitis

S.aureus is naturally found on the skin, but the dry, cracked skin associated with atopic dermatitis can lead to skin infections. A 2005 study found that applying a 0.02% farnesol and 5% xylitol emollient cream significantly reduced S.auerus on the skin of 17 atopic dermatitis participants – although did not evaluate if this was associated with fewer infections or any adverse effects on long-term use [15].

Seborrheic Dermatitis

It’s known that the Malassezia yeast is a key factor in the underlying pathology of dandruff and seborrheic dermatitis. We also know that Malassezia can form biofilms [16]. Some researchers have hypothesized that biofilms

There have been very few studies examining the ability of Malassezia yeasts to form biofilms although this has been demonstrated in some yeasts, particularly Candida

In studies evaluating Malassezia biofilms, no results have yet been of any direct clinical significance. A 2013 study showed that Malassezia biofilms exhibit significantly higher resistance to common antifungals (e.g. ketoconazole, miconazole) than isolated cells [14].

In addition, we also know that selenium sulfide is a very effective biofilm-dispersing agent [17].

It’s likely that acute dandruff treatments, with the exception of selenium sulfide, do not fully eradicate the biofilm, leading to a recurrence.

How to treat biofilms

There have been no clinical trials to date evaluating the effectiveness of different molecules, concentrations, and formulations on the treatment of biofilms associated with skin conditions. Research into biofilm disruption has identified several promising molecules, worthy of further testing in clinical trials:

Use a selenium sulfide shampoo

Selenium Sulfide, in 2.5% concentrations, is one of our go to treatments for moderate to severe cases of seb derm.

To learn that it is also a biofilm dispersing agent [17] is music to our ears.

Sugar alcohols

There are three sugar alcohols of note that may be effective at disrupting biofilms:

All are known to disrupt Streptococci, Candida, and P.gingivalis biofilms, with erythritol shown to be the most effective at altering the extracellular matrix. Erythritol has also been shown to synergistically work with antifungals, better than sorbitol or xylitol [4, 5]. Xylitol is a common additive in chewing gums to help reduce dental plaque (the most recognizable biofilm).

Lactoferricin

Wound healing is an important aspect of biofilm research. Lactoferricin can disrupt biofilms and promote wound healing [7]. When combined with xylitol the antibiotic effects are amplified – with a 2006 patent formulating the combination into a petroleum-based cream (e.g. Aquaphor) [8].

Acetic acid and honey are both effective wound dressings, and their effectiveness is possibly in part due to biofilm disruption [9, 10].

Farnesol

Farnesol is used by certain microorganisms to limit the expansion of the extracellular matrix in dense populations. A 2002 study showed that when combined with an antibiotic, farnesol was an effective treatment for methicillin-resistant S.aureus (MRSA) – although no animal or human trials have yet been published [6].

Cranberry juice

Cranberry is known to disrupt the biofilm of E.coli, S.aureus, and S.saprophyticus, preventing adherence to the bladder wall. It would, therefore, be logical to expect daily cranberry juice to reduce urinary tract infections, but a meta-analysis of 24 clinical trials covering 4473 participants found no significant effect – showing that research doesn’t reliably translate into clinical practice [11].

Taurolidine

Taurolidine is known to eradicate fungal biofilms. A pivotal 2004 clinical trial of 51 participants, with long-term intravenous catheters, showed a significant reduction in blood infections when the molecule was used in the locking mechanism – a method now widely adopted [12].

Summary

Biofilms are produced when microorganisms group together in communities to help protect against external stressors. They are complex biological systems, implicated in up to 80% of common infections, and have been shown to help develop and spread resistance to antibiotics.

Much of the research on biofilms has been on the underlying biology, with very few studies showing improved clinical outcomes due to biofilm disruption – although this is a promising area for future drug development. It’s likely that any novel treatments will work synergistically with antibiotics, which has already been shown with farnesol and xylitol.

There are too many caveats in our current understanding of biofilms, especially with how they relate to skin conditions, to make concrete recommendations.

If you have treatment-resistant seb derm, the most promising biofilm disrupting agent currently available in shampoos is likely to be either Selenium Sulfide or Xylitol.

For facial treatments, we recommend that you consider using Xylitol or Aquaphor

References

[1] D Mogosanu, G., M Grumezescu, A., Huang, K. S., E Bejenaru, L., & Bejenaru, C. (2015). Prevention of microbial communities: novel approaches based natural products. Current pharmaceutical biotechnology, 16(2), 94-111.
[2] Lynch, A. S., & Robertson, G. T. (2008). Bacterial and fungal biofilm infections. Annu. Rev. Med., 59, 415-428.
[3] Finkel, J. S., & Mitchell, A. P. (2011). Genetic control of Candida albicans biofilm development. Nature reviews. Microbiology, 9(2), 109.
[4] Hashino, E., Kuboniwa, M., Alghamdi, S. A., Yamaguchi, M., Yamamoto, R., Cho, H., & Amano, A. (2013). Erythritol alters microstructure and metabolomic profiles of biofilm composed of Streptococcus gordonii and Porphyromonas gingi
[5] Ichikawa, T., Yano, Y., Fujita, Y., Kashiwabara, T., & Nagao, K. (2008). The enhancement effect of three sugar alcohols on the fungicidal effect of benzethonium chloride toward Candida albicans. journal of dentistry, 36(11), 965-968.
[6] Ramage, G., Saville, S. P., Wickes, B. L., & López-Ribot, J. L. (2002). Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule. Applied and environmental microbiology, 68(11), 5459-5463.
[7] Ashby, B., Garrett, Q., & Willcox, M. (2011). Bovine lactoferrin structures promoting corneal epithelial wound healing in vitro. Investigative ophthalmology & visual science, 52(5), 2719-2726.
[8] Wolcott, R. (2006). U.S. Patent Application No. 11/601,858.
[9] Bjarnsholt, T., Alhede, M., Jensen, P. Ø., Nielsen, A. K., Johansen, H. K., Homøe, P., … & Kirketerp-Møller, K. (2015). Antibiofilm properties of acetic acid. Advances in wound care, 4(7), 363-372.
[10] Tyagi, S. P., Sinha, D. J., Garg, P., Singh, U. P., Mishra, C. C., & Nagpal, R. (2013). Comparison of antimicrobial efficacy of propolis, Morinda citrifolia, Azadirachta indica (Neem) and 5% sodium hypochlorite on Candida albicans biofilm formed on tooth substrate: An in-vitro study. Journal of conservative dentistry: JCD, 16(6), 532.
[11] Jepson, R. G., Williams, G., & Craig, J. C. (2012). Cranberries for preventing urinary tract infections. The Cochrane Library.
[12] Betjes, M. G., & van Agteren, M. (2004). Prevention of dialysis catheter-related sepsis with a citrate–taurolidine-containing lock solution. Nephrology Dialysis Transplantation, 19(6), 1546-1551.
[13] Donlan, R. M. (2002). Biofilms: microbial life on surfaces. Emerging infectious diseases, 8(9), 881.
[14] Figueredo, L. A., Cafarchia, C., & Otranto, D. (2013). Antifungal susceptibility of Malassezia pachydermatis biofilm. Medical mycology, 51(8), 863-867.
[15] Masako, K., Yusuke, K., Hideyuki, I., Atsuko, M., Yoshiki, M., Kayoko, M., & Makoto, K. (2005). A novel method to control the balance of skin microflora: Part 2. A study to assess the effect of a cream containing farnesol and xylitol on atopic dry skin. Journal of dermatological science, 38(3), 207-213.
[16] Ramage G, Mowat E, Jones B, Williams C, Lopez-Ribot J (2009) Our Current Understanding of Fungal Biofilms. Crit Rev Microbiol 35: 340-355.
[17] Allen HB, Goyal K, Ogrich L, Joshi S (2015) Biofilm Formation by Malassezia Furfur/Ovale as a Possible Mechanism of Pathogenesis in Tinea Versicolor. J Clin Exp Dermatol Res 6:311. doi:10.4172/2155-9554.10000311

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