Skin Deep - Clinical & Cosmetic Dermatology Blog

Skin Deep is a blog for dermatologists and skin care professionals with focus on theoretical, cosmetic and aesthetic dermatology. This blog is associated with ‘Dermatologists Sans Borders’ one of the largest curated groups of skin care professionals on facebook. If you are looking for non-technical information, please visit http://skinhelpdesk.com


Chicken or the egg in Acne?


This article[1] reiterates the role of antimicrobial peptides (AMP), the body’s innate antimicrobial system in the pathogenesis and management of acne. Yes, there is a paradox here! AMP because of its anti-p.acnes action may improve acne while its proinflammatory properties may worsen it. It is not known whether p.acnes indirectly causes inflammatory acne by promoting AMP production. The authors examines several endogenous AMPs and gets unduly enticed in this Chicken-Egg paradox making too many speculations. However the bottom line seems to be simple and straightforward: Structurally modified AMPs and AMPs from other species with less proinflammatory properties may be useful in acne. Full article is available from the cited URL.[1]
Acne vulgaris
Acne vulgaris (Photo credit: Wikipedia)

Here is a head-to-head comparison of three questionnaires to screen for psoriatic arthritis.[2] All three questionnaires (PEST, Toronto Psoriatic Arthritis Screen (ToPAS) and PASE) were found to be effective for the purpose.

References:
1. Harder J, Tsuruta D, Murakami M, Kurokawa I. What is the role of antimicrobial peptides (AMP) in acne vulgaris? Exp Dermatol. 2013 Apr;p. n/a. Available from: http://dx.doi.org/10.1111/exd.12159.

2. Coates LC, Aslam T, Al Balushi F, Burden AD, Burden-The E, Caperon AR, et al. Comparison of three screening tools to detect psoriatic arthritis in patients with psoriasis (CONTEST study). The British journal of dermatology. 2013 Apr;168(4):802-807. Available from: http://dx.doi.org/10.1111/bjd.12190.


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How to Calculate Your Age

Recently I added one more exciting function to DermKnowledgeBASE (DKB). Now you can search for clinical differential diagnosis for any dermatological condition by clicking here. The consult algorithm has also undergone some refinement. Thanks for all the feedback. The second read cycle is nearing completion. The sensitivity may improve as more and more data becomes available. The Colombian project is progressing well. If anybody else is using DKB webservices, few recent modifications have been made. Do let me know if you need any information. Check out the differential diagnosis for lichen sclerosus et atrophicus from DKB. BTW did anyone use the consult function recently?
The first two principal components after PCA u...
The first two principal components after PCA using a Gaussian kernel (Photo credit: Wikipedia)

Johnson & Johnson research team has proposed a new concept to evaluate the efficacy of anti-ageing treatments and products. The concept seems to be interesting. Basically the cutaneous ageing is a combination of several measurable changes that are inter-correlated. Though the mathematics behind normalized projection on the first Principal Component Analysis (PCA) axis can be quite complicated, in essence a single value that summarises several factors is proposed as the ‘skin aging index’. They have used the method to test one of their products. I could only access the abstract.[1]
Bee hoon
Bee hoon (Photo credit: benoit.mortgat)

During my series on beauty peptides, I explored the concept of collagen fragments tricking the body into producing fresh collagen. However there are other ways of stimulating collagen production and to inhibit the activity of the enzyme that breaks down collagen, MMP-1. This study suggests that Phosphatidylserine (PS) can be used as a therapeutic agent to prevent UVB-induced skin photoaging and perhaps even natural skin aging by downregulating MAPKS/AP-1 signaling pathways.[2] PS is a diet supplement commonly used by athletes to prevent muscle soreness. PS is abundant in meat, brain, liver and kidney.

References

1. Nkengne, Alex et al. "The skin aging index: a new approach for documenting anti‐aging products or procedures." Skin Research and Technology (2013).

2. Lee, Sang‐Hoon et al. "Protective effect and mechanism of phosphatidylserine in UVB‐induced human dermal fibroblasts." European Journal of Lipid Science and Technology (2013).

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How to improve the lines on your face

When I concluded my post on Argireline I mentioned that Argireline is unlikely to have significant muscle relaxant effect like Botulinum Neurotoxin (BoNT). But how do you objectively measure the ‘therapeutic’ muscle weakness induced by cosmetic treatments like BoNT injections. Surely we cannot rely on electromyography for such mundane indications.

Finally, scientists from Stony Brook University has adapted an image processing algorithm for this purpose.[1] Basically Digital Image Speckle Correlation (DISC) is an optical method to measure deformation on an object surface as the wrinkles formed on muscle contraction. Confused? Let me try to explain the concept in simple terms. Imagine a rubber sheet with a grid printed on it. If you pull this rubber sheet in various directions, the grid will get deformed. You can measure the movement and indirectly the pulling force by studying the deformity in the grid pattern. Now replace the rubber sheet with the skin and the grid with the pore pattern. Now you get the idea, don't you?
East Campus: Stony Brook University Medical Center
East Campus: Stony Brook University Medical Center (Photo credit: Wikipedia)

The authors have done a pilot study to assess the clinical relevance by comparing the results of the algorithm with a plastic surgeon’s assessment score (SGA) and the patients self assessment (FLO-11) and found some interesting findings (though it is a pilot study with insufficient power to prove anything). The muscles show a phase of hyperkinesis when the effect of BoNT wears off! A common question asked by the patients in our practice is whether ‘not taking’ regular BOTO@ can worsen existing wrinkles once you initiate treatment. We always say an emphatic NO. Now think again!

speckled leaf
speckled leaf (Photo credit: psyberartist)
The patient assessments were positive even during the hyperkinesis phase. Cosmetic dermatology is a specialty where patients can be happy for wrong reasons! If you are new to BoNT injections there is good news for you too. The algorithm can predict for you the best site and quantity of BoNT/A to inject!

So is this algorithm a game changer? Though the algorithm is objective, there is still a subjective component that we cannot avoid. When you instruct a patient to raise the eyebrows, frown or smile for the pre-procedure assessment, how and to what extent he does that is still up to him. So the pretreatment evaluation is still subjective. I believe that is the reason for the gross perceived hyperkinesis after 4-6 months.

Bottom line: This is a good research tool. A sufficiently powered study using this method could call Argireline’s  bluff and find the winner in the Boto@ v/s Dyspo@@ war. It could even be a patient education tool. But it is unlikely to replace your subjective judgement regarding site and quantity of injection. Some things in cosmetic dermatology are meant to be subjective!

Special thanks to Divya Bhatnagar, the main author[2] and the rest of the research team (Nicole Conkling, Miriam Rafailovich, Brett T. Phillips, Duc T. Bui, Sami U. Khan and Alexander B. Dagum).

Disclaimer: Argireline is a registered trademark.

References:

1. An in vivo analysis of the effect and duration of treatment with ..." 2013. 16 Apr. 2013
http://www.ncbi.nlm.nih.gov/pubmed/23565582

2. Bhatnagar, Divya et al. "An in vivo analysis of the effect and duration of treatment with botulinum toxin type A using digital image speckle correlation." Skin Research and Technology (2013).



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The Vitiligo Vaccine


Despite years of research, Vitiligo is still an enigma. Vitiligo could well be the most “serious” cosmetic disorder of the skin, in terms of the psychological morbidity it causes especially on pigmented skin. Even now we are not sure whether vitiligo is autoimmune, genetic, oxidative stress, neural, viral or a combination of all the above. Treatment of vitiligo, just like fashion, keeps changing the favourite, every now and then. Immunosuppressants had their time. Phototherapy was a clear favourite before the reign of melanocyte transplant began.

Česky: Splývající makulózní léze při vitiligu ...
Vitiligo (Photo credit: Wikipedia)
All these years vitiligo was never viewed as a preventable disease. Though it is still early days, latest genomic techniques are suggesting that vitiligo is a genomic vaccine preventable condition! The vaccine could also improve established cases of vitiligo. A chaperone (molecules assisting the folding process of proteins) called heat shock protein 70 (HSP70) is implicated in the pathogenesis of vitiligo. A genetically modified HSP70 when administered as a vaccine prevented and cured vitiligo in mice.[1]

Let us hope that this heat shock protein successfully negotiates the long gap between mice and humans. Hope the vaccine will not ‘shock’ us by degenerating into another ‘hot’ fashion. I shall soon discuss the  latest trends in vitiligo genomics in my informatics blog. Meanwhile take a look at this new concept of ‘Vitiligo Potential Repigmentation Index’.[2]

A recent study showed that a combination of afamelanotide implant and NB-UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB-UV-B monotherapy. The response was more noticeable in patients with SPTs IV to VI.[3]

Share below to see the references.

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10 reasons why nanobodies are better antibodies

Which is the latest monoclonal antibody for psoriasis? ----mab? (Feel free to use any four letters to fill in the blanks. Don't worry if it sounds strange today, it may not tomorrow). This will be followed by a series of expensive trials to prove the superiority of @@@mab of today to that of yesterday.

Polygon Medical Animation - Monoclonal Antibod...
Polygon Medical Animation - Monoclonal Antibody Therapy (Photo credit: Polygon Medical Animation)
Finally, there is a new technology in the horizon. The new technology actually simplifies things rather than complicate it. Ablynx, the developer observed what camels do with their antibodies and expunged unwanted parts of our conventional antibody. What remained was the single monomeric variable antibody domain. To their surprise, they found that the remaining antibody fragment  was more specific, had better affinity, low inherent toxicity, was easy to manufacture (hence cheaper) and could be administered through routes other than injection! Sounds like fairy tale? But it is true. Let me introduce the new hero Nanobody![1]

Comparison of (brown: human, blue: non-human):...
Comparison of (brown: human, blue: non-human): top row: mouse, chimeric bottom row: humanized, chimeric/humanized, human The substems according to the are shown below each antibody. (Photo credit: Wikipedia)
Most of the nanobodies are still on the drawing board. Some nanobodies may be specific enough to target fibrils in advanced stages of amyloid formation making it useful in Parkinsons.[2] A anti-Malassezia nanobody stable enough to be used in shampoos for dandruff is already being studied.[3] Very soon we might see a TV commercial of Embrel shampoo!

BTW, I have recently added a www to non-www redirect to this website. Please inform me if you notice any problems especially those using DKB webservices.

Disclaimer: Nanobody and Embrel are registered trade marks.

References:

1. "Understanding Nanobodies | Ablynx." 2010. 9 Apr. 2013 URL: http://www.ablynx.com/en/research-development/nanobody-technology/understanding-nanobodies/

2. Vuchelen, Anneleen et al. "1H, 13C and 15N assignments of a camelid nanobody directed against human α-synuclein." Biomolecular NMR assignments 3.2 (2009): 231-233.

3. Dolk, Edward et al. "Isolation of llama antibody fragments for prevention of dandruff by phage display in shampoo." Applied and environmental microbiology 71.1 (2005): 442-450.


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eDerm Systems - A futuristic EHR for dermatology

When Mr Andrew Queen, the President of eDerm Systems and me (sitting half way across the world) seamlessly completed an online demo of the new eDerm Electronic Health Records (EHR) for dermatology, I did not ask one obvious question as I knew the answer already. Why an EHR specifically for dermatology? Just as I mentioned in ONTODerm, dermatology is different from other medical specialities with different requirements. Localisation of the lesion and an accurate description of its appearance is of paramount importance to us dermatologists. eDerm has done a good job in simplifying both to the click of a button using the latest technology making our documentation job a lot easier. Your module would be running on your ipad, making lesional description almost unnecessary as your camera can capture it more accurately!
(Image Credit: eDerm Systems website)

How is it different from other EHRs? Firstly it is cloud based (pardon the technology jargon). In simple terms the technology makes sharing between your front desk, your home computer, your other clinics, your insurance provider, your lab and your chemist as easy as a walk in the cloud. But a local copy of the data is also stored in your device, so that you can access data even when internet connection is not available. System updates are seamless almost like your Google chrome that updates on its own. Secondly it is self learning. As you use it more and more, it will recognise your patterns and make suggestion according to your taste. Finally it is specifically designed for dermatology by dermatologists, so you can expect the system to be intelligent!

The system however is a bit too expensive for a cloud based system. Data security is an issue for cloud based EHRs. An intuitive advanced search function combining various factors (using boolean logic) to retrieve publication ready data is also lacking. Modules for mole mapping, fetching evidence based practice guidelines and drug interaction checker would have been useful too.

Please share below to visit eDerm Systems website


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The Embrace That SNAPS the SNARE - Argireline Part 2


Please read Argireline Part 1 and the full series here.

Acetyl hexapeptide-3 has one major advantage. BoNT/A causes permanent destruction of SNAP-25 of the SNARE complex, triggering neuronal sprout formation and a steady recovery. Acetyl hexapeptide-3 acts like a competitive inhibitor of SNAP-25, so this recovery mechanism is not triggered. It is also claimed to have an independent effect on fibroblast contraction that augments collagen synthesis. But there are many prominent disadvantages as well.

Detailed view of a neuromuscular junction: 1. ...
Detailed view of a neuromuscular junction: 1. Presynaptic terminal 2. Sarcolemma 3. Synaptic vesicle 4. Nicotinic acetylcholine receptor 5. Mitochondrion (Photo credit: Wikipedia)
In my previous post on 3 villains, I mentioned about stability, penetration and degradation of peptide molecules. This article claims that Acetyl hexapeptide-3 is good enough to combat this villians.[1] But there are two other mysterious villains in this story. Before I expose them, some shameless self promotion again.

In my article [2] (self archived preprint here) I discussed the importance of the binding of BONT/A to the SV2 receptor that facilitates its neuronal penetration. This binding is mediated by a domain of BONT/A different from its active site. Acetyl hexapeptide-3 does not have this domain. So how does it reach the inside of the neuron? (Read this on Rational Peptide Design)

BONT/A injectors would agree that, a muscle relaxant could be cosmetically enhancing if administered in the right places. A non-localised effect is unlikely to be beneficial. Does it cause sagging?

Acetyl hexapeptide-3 (like most peptides) did not have any experimental proof of efficacy. Now it has! This study[3] shows that it can increase type I collagen (but paradoxically reduces type III, problem!!). Why did they study the effect on collagen synthesis when it is sold as a muscle relaxant?

And finally, an RCT on Acetyl hexapeptide-3 that shows promising results![4] But wait, Did you see the conclusion.
“In the objective evaluation, the parameters of roughness were all decreased in the argireline group (p < 0.01), while no decrease was obvious in the placebo group (p > 0.05).” 
Separate P values for intervention arm and placebo arm. I don't have access to full article, but this means only one thing to me. They were scared (or want to hide) the actual intervention-placebo comparison. What do you think?

Embiodea
Embiodea (Photo credit: beapen)
The bottom line: Acetyl hexapeptide-3 is unlikely to have remarkable muscle relaxant effect, but could have a non-specific pro collagen effect with a mechanism of action different from other collagen fragments, I discussed before. A mixture of both (Argireline and Matrixyl) may give additive effect.

References:
1. Ruiz, MA et al. "Preparation and stability of cosmetic formulations with an anti-aging peptide." Journal of cosmetic science 58.2 (2007): 157.

2. Eapen, Bell Raj. "Molecular biology of botulinum neurotoxin serotype A: a cosmetic perspective." Journal of cosmetic dermatology 7.3 (2008): 221-225.

3. Wang, Yuan et al. "The anti-wrinkle efficacy of Argireline." Journal of Cosmetic and Laser Therapy 0 (2013): 1-5.

4. Wang, Yuan et al. "The Anti-Wrinkle Efficacy of Argireline, a Synthetic Hexapeptide, in Chinese Subjects." American journal of clinical dermatology (2013): 1-7.

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Pigment Map and Skin Genomics Projects


I have this habit of making flowcharts to organise information. It helps in visualising information in a broad context. It could also give unique insights sometimes.

Recently I found that there are several online flowchart creation sites. More advanced version of flowcharts are called mind maps. These online sites support collaborative flowchart creation. Don’t you think it is cool?? Many domain experts contributing to a huge online mind map that summarises a complicated topic that everybody can refer to.
Mind Mapping
Mind Mapping (Photo credit: sirwiseowl)

I started making some mind maps few months back and made it publicly available from my website to draw the attention of domain experts. Google quickly indexed these pages and these pages have become relatively popular in a short time. But these mind maps are nowhere near completion. The most popular one is the Pigment Map Project (PMP) to summarise molecular and biochemical factors in pigment production and control. The other projects are Skin Genomics Project (SGP) [This page gets many hits for the search term skingenomics!], Skin Barrier Project (SBP) and Cutaneous Fibrosis Project (CFP). The last two were added couple of days back only. Hope these pages would become popular too.

In spite of google contributing to the traffic to these pages, nobody has expressed any interest in contributing to these mind maps. So If you like the concept delve right in here ( http://gulfdoctor.net/mindmaps ) All the details and instructions are available on the respective project pages. Link to a demonstration video is also provided.

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About Me

As a Dermatologist and Informatician my research mainly involves application of bioinformatics techniques and tools in dermatological conditions. However my research interests are varied and I have publications in areas ranging from artificial intelligence, sequence analysis, systems biology, ontology development, microarray analysis, immunology, computational biology and clinical dermatology. I am also interested in eHealth, Health Informatics and Health Policy.

Address

Bell Raj Eapen
Hamilton, ON
Canada