I estimate that about 70% of my patients have good results, which means that 3 out of 10 patients are unimpressed.  I am surrounded by dermatology residents and fellows who call it as they see it, and they give me that quizzical look when I recount the original study outcomes, wherein every patient could see obvious improvement.  We are careful to take standard digital images and we compare them diligently. True, we don’t employ the three dimensional Vector system, and neither do I perform ultrasound or MRIs on patients, but frankly if they can’t feel or see the difference, what’s the point? It’s not enough for us to be satisfied that 100% of patients have measureable improvement by U/S or MRI.  Innovativel devices can be killed by hype.

So why are some investigators seeing results in all their patients, and others not. This was one of the issues discussed informally by Christine Dierickx, Henry Chan, Rox Anderson, Arielle Kauvar, and Chris Zachary in Paris recently at Les Journées Parisiennes du Laser 2010 conference, a premier meeting of French laser specialists. Henry Chan has also experienced some patients with little improvement in Hong Kong. Arielle Kauvar has noticed improvement in all her patients. We need to determine from Zeltiq users worldwide whether there are outcome differentials, and if so whether these are related to age and gender, or anatomic, geographic, ethnic, technique or other differences between our patient populations.  These might then provide clues as to the cause of this disparity in outcomes.

While musing over lunch, no doubt thinking ‘we are what we eat’, Rox Anderson suggested that the Californian diet was probably lower in saturated and trans fats, and that their fat might ‘freeze’ differently, whereas the East Coasters who enjoy more Philly cheese steak sandwiches might have longer fatty acid chain adipose tissue, with a more responsive outcome.  While humorous, this thought has merit, and would be easy to study, even retrospectively.

Also discussed was the question of painful responses. Two patients with prolonged and severe pain post-Zeltiq were previously reported in this Blog. At the time they seemed to be absolute outliers.  However, it is clear that there have been a very small number of similar but less extreme painful responses, lasting several weeks. The cause of this painful response is not understood, but could be related to the acute panniculitis itself, or possibly a vascular event, an acute neuritis, or some other noxious stimulus to the fat, the underlying fascia, or possibly the underlying muscle.  Rox reminded us that the glomus cell is involved in the control of vascular shunting in a cold environment, and that these shunts can be associated with significant pain. Given that the Zeltiq suction device effectively shuts off the vascular supply to the affected skin and subcutaneous tissue for 60 minutes, one could predict hypoxic tissue responses, despite the protective nature of the cooling.

The normal sequelae of numbness, a modest burning sensation, and other paresthesias are commonplace for several weeks or months.  All patients should be informed about these. Further, these side effects might be used therapeutically in order to control chronic cutaneous pain syndromes, such as post herpetic neuralgia.

The issues are twofold, and both are pernicious. Device companies are being squeezed by organizers of certain CME meetings in a pay now and pay later ruse. Companies sign up months in advance to exhibit at a cost of $5-10K. Then they receive a call one to two weeks prior to the actual meeting and are invited to pay another $5-10K to have their device discussed at the podium. No pay … no play. I have know speakers disinvited from talking about a certain generic technology ‘because their sponsor refused to pay up’ in this double squeeze play, and ‘thus their talk would no longer be needed’. Further, new talks are susbstituted by inferior product-specific presentations merely because company ‘B’ agreed to pay up.  Clearly this is flouting CME regulations, and more importantly, is an unhealthy manipulation of power and trust.

It might seem very Pollyannaish of me to hold these sentiments, but there you have it.

Conversely, I would hold the somewhat controversial view that product specific presentations are absolutely appropriate, if billed as such. The increasingly popular trend is for meetings to include technology exhibits or forums as side shows that are well funded and are represented as being exactly what they are, namely product specific promotional information sessions. Much akin to separation of church from state, there is clear separation from the main scientific sessions, and this is fine as far as I am concerned.

As a Medical Director of the SDEF meetings, I am aware that we used to do things differently in the old days ….. But now, all the CME scientific sessions need to be free of commercial bias. The meeting attendees are not always well informed enough to know when they are being snowed. Maintaining an even keel can be difficult, but common sense allows an impartial moderator to steer the content in a straightforward and candid manner. The integrity of a meeting is often based on the integrity of the session moderators, and has little to do with a boatload of CME regulations.

No amount of regulation will prevent the type of unethical end-run that some CME conference organizers are using to line their pockets at the expense of truth.  So this is really a call for moderation, and for achieving a balance, for if we do not get it right, then we will reap the consequences.

The CME staff are so confused about what is acceptable that presentations are often changed by them without permission, often at the last minute and without informing the speakers.

Device (and drug)  names are removed from PowerPoint slides leaving the audience without any basis upon which to understand the difference between one device or another.

Eyes and periorbital regions are covered in photographs, despite signed use agreements, even in cases depicting pre and post eyelid surgery.

Requirement for talks to be submitted weeks or months before the meetings …. (is anyone really that organized?)

“The pendulum has swung too far”, said Dr Zachary. “It’s time for reason to set in”. If doctors can’t tell the difference between science and a sales job, then our medical schools have failed to educate them appropriately”.

“Low level light (LLL) is going to be used by most of us in ten years when we can work out how best to manipulate it”. It’s all related to mitochondrial absorption of light. The cytochrome (cell color) absorption of specific wavelengths (630, 670, 810, 900 nm) can control oxygenation of tissue by affecting the nitric oxide (NO) switch. Stress caused by surgery or other injury induces copious amounts of NO, which competes with oxygen tissue binding sites. LLL pulls NO off these key binding sites which allows greater tissue oxygenation (read more by Harvey Whelan   and Uri Oron. This is likely to help all ischemic tissue states, and has even been found to have a significant beneficial effect on acute stroke patients. The exception that both Dr Anderson and Dr Matt Avram stated was that they had a hard time believing the claims made by Zerona that inches could be lost with the use of this device.

Fractionation of Laser Energy

Rox Anderson MD discussed the microscopic effects of fractionated laser surgery at the FSDDS meeting in Naples, FL, Sunday 31^st May. Each area of injury is like a tiny murder, which is pretty innocuous on the grand scale of things, and induces new healing, new collagen. The maximum depth for the non ablative devices is about 1.2 mm “we’re not going to get much deeper than that’, said Anderson.   They also do a pretty good job with fine superficial telangiectases and for atrophic skin conditions. ‘Don’t be in a hurry, because some of these great results take 5 or 6 treatments’.

He reminded us of Dr Jil Waibel’s work who has induced remodeling of scars on a microscopic scale, which has made very significant changes to hypertrophic scars after burns and surgery.  Also, Chad Hivnor MD USAF, who has been treating shrapnel scars on the men and women coming back from the Afghan and Iraq wars. Fractionated ablative surgery has been found to be very useful in reducing both hypertrophic and atrophic scars.

Combination use of fractionated ablative lasers with Methyl-ALA (porphyrin precursor) indicates 10-100 times more agent gets into the deeper skin than would otherwise. There is a very fast uptake of any molecule, which will also include bugs ….. “there’s a ying and yang for everything”. Massaging the topical agent makes no difference in its uptake.

Scarring can occur if the technique and parameters are incorrect, as evidenced by the work by Matt Avram and Christopher Zachary published in separate articles last year.

It’s impossible for a potential client, be they a prospective patient or purchaser of these devices, to make a serious and clear decision about the ‘right’ device, when these studies, vetted and stamped with the approval of the Journal editors and reviewers, are so clearly full of nonsense. Dr Christopher Zachary, Professor and Chair of UC Irvine’s department of dermatology, together with John Allison PhD and Nazanin Saedi MD, made this presentation to the Dermatology/Plastic section of the American Society for Laser Medicine and Surgery’s annual meeting in Phoenix.

Comments from our colleagues ran the gamut from brilliant to entertaining to empowering.  Great social events, phenomenal breakfasts and full dinner buffets. Despite the great weather, the auditorium was at near capacity with the attendees being interactive, enthusiastic, and involved. Piece de la resistance was the trademark high definition live video demonstration of fillers and neurotoxins.

This year has seen a 10% increase in attendence at a time of global financial recession. “It’s very encouraging to see our colleagues investing time, energy and money into quality education” said Joe Fowler MD, director of SDEF meetings along with David Goldberg and Christopher Zachary.

The SDEF meetings are required to adhere to strict compliance guidelines which are enshrined in a new Elsevier memorandum on the subject, compiled and produced with quality of education as its major goal. “These are difficult times of over-regulation” stated Dr Zachary, “but we have got ahead of this tiger. Pharmaceutical and device companies can count on Elsevier to get it right, for their protection, and for the protection of the industry that supports them”.

Never in doubt, and always with conviction, Dr Leonardi laid out reasons he felt that some studies were being pushed at the expense of full disclosure.  He also took aim at those physicians in the community (and also in the audience) who participated in these studies.  He intimated that some of these studies had adverse events which were serious, and yet not emphasiszed or adequately reported. 

To be fair to Abbott, there does appear to have been a significant amount of effort on their part with regard to updating information and consent forms to reflect newly discovered AEs. 

However, this type of discussion is a healthy hallmark of the Hawaii Derm Seminar, where speakers feel free to criticize companies and even their own colleagues in a full and frank manner. Only in this way can we seek out fact from fiction…..

Joe Fowler MD addressing the meeting attendees at the 34th Hawaii Dermatology Seminar.  The Hawaii Derm Seminar is the original and premier Hawaii dermatology meeting. This year has seen a 10 % growth in attendees, many of whom are the younger set. All are welcome to enjoy participating in these extraordinarily beautiful surroundings where they will receive the real facts without commercial bias.

Skin Barrier and its effect on eczema. Joe Fowler MD.

Skin barrier is not simply an esoteric matter.Barrier dysfunction in a normal individual is not such a big deal. But in those who have functional problems, it is one of the most important components to control. Barrier dysfunction can induce epidermal injury and associated inflammation, and is related to age, UV, stress, low humidity, skin disease, and genetic factors.  Dysfuntion is normally followed by barrier repair.

Exogenous causes of barrier dysfuntion include both irritant exposures and allergic contactants. Irritant exposures include friction, harsh or excessive cleansing, hydrocarbon solvents., acids and alkalis, and photodamage.  Allergic contactants include industrial and skin care products, medications, gloves, cosmeceuticals among others.  These all damage the stratum corneum, which has a biosensor function. Natural moisturizing factor (NMF), coined by British scientists,  is very hygroscopic, is produced within the corneocytes, and is a “soup” of amino acids. Profillagrin is the major component of NMF which breaks down to fillagrinand amino acids.  Considerable literature on this subject now exists.  NMF production is blocked or reduced with UVB exposure.

So why isn’t Vaseline good enough to prevent barrier problems? Peter Elias MD PhD showed in normal subjects that after damaging the skin barrier, natural ‘healing’ occurs over course about 8 hours (50% improvement), but addition of (non-physiologic) petrolatum tends to slow this process.  Add a gemish of ceramide and other physiologic mixtures, you get much better recovery over time.  So physiologic barriers are important, and non-physiologic agents such as vaseline may not be as good as we thought.

Many barrier creams have been touted as being useful without much evidence. Newer agents such as Tetrix Cream, and Neo-Salus Foam, (no generic names available)  both enhance skin barrier to allergens and irritants. They both have good data on barrier function, in patch testing studies and on hand eczema.

IvyBlock lotion blocks poison ivy.  It’s quite effective, and well established to block and protect against urushiol in poison ivy, oak, and sumac. Available OTC.

Regular moisturizers can be helpful in situations of mild xerosis or tansient stratum corneumdamage. Not so good for subjects with prolonged  inflammation, poor inherent repair such as atopy.   A balanced mixture of ceramides1,3,6 may be important.  The delayed release of components may prolong therapeutic effect. Three brands CeraVe, Mumyx, and Epiceram.

Guy Webster MD  Acne from an Expert – Drugs, Diet, and More

Antibiotic resistance …. why care?  Because acne is becomingharder to treat. Resistant strains are becomingmore common, including MRSA and Vanco resistant enterococcus.  Safety of longterm antibiotics is likely. Concerns over association with breast cancer is likely coincidental; statistical correlations aren’t always valid.

Which antibiotics are most effective?Combining antibiotics and benzoyl peroxide (BPO) is synergistic; erythromycin or clindamycin alone can be made three times more effective when used in combination with BPO.  And clindamycin with BPO is currently quite effective in comparison to other antibiotic regimes.

Isotretinoin and its complications…. apart from the usual dry lips, dry skin, dry eyes, high triglycerides, and acne flare, there are several much less common, but more significant issues. Elevated CK, AST and ALT enzymes,  decreased night vision, depression, acne fulminans have all been reported. The question that arises in young athletes with  acne is, should they stop or slow down their workout routine to prevent  high muscle enzyme levels. Individual assessment needed, but Dr Webster recommends slowing up the workouts ….

Vincent Deleo MD discusses Vitamin-D, Sunscreens and You!

A review of the traditional messages concerning sunlight protection vs new advice that we give to patients. A need to recognize that we should advise reasonable precautions with which the public can live.

And then came Michael HolickMD NEJM 357, 2007, stating his views on vitamin D status and sunlight.

UVB is still the major cause of premature skin aging, although we recongnize that UVA, which penetrates much deeper, is clearly also relevant.

Do sunscreens work?  Yes, if you use them correctly, and most people don’t. Do they prevent skin cancer?No adequate data to assure us that sunscreens protect us against BCC or melanoma. But they do prevent AKs and SCCs. Do they prevent photoaging? Yes probably, but very difficult to do these studies because they need to be long term studies.

25-OH Vitamin D .. what is normal?  Key message here is that most of us are deficient!  Deficient (1-10 ng/ml), Insufficient (10-20 ng.ml), Hypovitaminosis (20-30 ng/ml), Adequate >31 ng/ml.

Normal Vitamin-D levels are found in only 43% white individuals, 7.8% African Americans, and 20% Hispanics. Fully 50% of blacks are deficient in Vit D for normal health.  What are the problems with low Vit D? Decreased bone density, hip fractures, falls, especially in the elderly.  There is a 26 % increase risk of deathfrom any cause. Other diseases that may be associated with low Vitamin-D levels are breast cancer, colon cancer, type I and II diabetes, heart disease, MS, lower survival in melanoma and non-Hodgkins lymphoma.

Vitamin D-3 taken as a supplement is sufficient to bring serum levels up to normal levels. Recent recommendation are that all adults need 1000 – 2000 international units per day, and that  children receive 400 iu per day.

Are we winning the war against excessive sun light? Only 34% of children who are from 12-18 years actually use sun block (which is no big surprise since they all think they are going to live forever …) 

Tanning devices are regulated as Class I medical devices, like tongue depressors, which is rediculous and this has always been more than half the problem. Noonewas taking this seriously ….   But now the FDA is taking action against tanning salons, their regulation,  and what they can claim in terms of ‘tanning being healthy’.  The cost of doing business is going to increase, and the public are going to hear more about the dangers of tanning. But these tanning salons are not going away any time soon …..

AAD recommendations include sunscreen use with SPF 30 or greater, protect your children, use Vit-D supplements, avoid tanning beds, check your skin at least annually.

Future regulations regarding suncreens ….  SPF will be known as Sunburn Protection Factor, rather than Sun Protection Factor … SPF ratings will be rated as Low (2-15), Medium (15-30), High (30-50), Highest >50.   Stability and longevity will be referred to as water resistant (40 mins), or very water resistant (80 mins).

UVA rating… in vivo and in vitro testing is coming. Of these two measures, the manufacturers may use the lower of the two scores. The product label will have from one star to four stars based on these in vivo and in vitro measures.

Grenz-Rays are back!

According to Joe Fowler MD, Grenz rays are safe, effective, and ecomomical. Grenz rays are “soft” X-rays with a half-value layer of < 1 mm. There is no detectable radiation at 3-4 feet, and essentially no radiation precautions are required. They should be used in localized areas (6-12 inches circumference) and are very useful on localized chronic eczmatous areas such as the hands, scalp, and genitalia.  I am personally delighted to hear Dr Fowler say this, since I saw several patients with severe hand eczema ‘cured’ with this therapy back in 1980-85 at St John’s Hospital in London …..