How to Start a Walk-in Dermatology Clinic

Dale Westrom, MD, PhD

Why did Dr. Westrom start his walk-in clinic? In 2007, Dr. Westrom read an article by Jack Resneck stating that it was easier to see a dermatologist for Botox® than a changing mole. Dr. Westrom who felt that the article reflected very poorly on our profession took this article very seriously.

Dr. Westrom practices with four dermatologists and a nurse practitioner.  He typically sees six patients per hour, so he and his office manager decided that he would stop at 3:45 and open the walk-in clinic from 4:00-5:00. Dr Westrom’s practice averages about 15 patients per session. (4 days a week in one office and 3 days a week in another office) In the walk-in clinic, he tends to see more new patients and more cash-paying patients.

The walk-in clinic would best be characterized as “speed derm”.  The key to its success is making a timely and accurate diagnosis, treating the skin condition or doing a biopsy and then setting up any necessary follow-up visit and moving onto the next patient. The urgent dermatology care clinic is not for patients with complex problems requiring a lengthy consultation.  This point is emphasized to referring physicians/clinics and to patients who sign in.  “This is a great way to build one’s practice through new patients and retaining current patients,” added Dr. Westrom. The clinic works well for patients who have irregular schedules and cannot necessarily plan several weeks out as well as for those patients who recognize that their problem “can’t wait” to be seen.

The patients who come into Dr. Westrom’s clinic  receive a notice explaining that “the purpose of this clinic is to evaluate and treat single urgent skin problems, e.g. changing or new growths, infections, severe rashes, etc.   The intention of this clinic is to detect skin cancers early, treat infections before they spread, and control rapidly developing rashes. Patients will be seen in the order that their paperwork has been completed and the chart is “put up”. “First chart up…. first seen”.  Understandably, established patients will usually have most of their paperwork completed before they sign in so they may be seen before someone ahead of them on the list while that person’s paperwork is being completed.  Everyone who signs in by the end of the scheduled clinic hours will be seen, no matter how long it takes.  Because of the urgent nature of their clinic and the fact that it is being conducted at the end of the day, no HMO patients will be seen without a referral in hand unless they sign a waiver and agree to pay privately (no retroactive referrals will be accepted).”

In a walk-in clinic, patients will be seen on a first ready/first served basis. It is important that the staff understand that during the walk-in clinic, no appointments may be scheduled. When running a walk-in clinic it is important for you and your staff to consider the variety of insurance reimbursement profiles regarding procedures.  Staff training and standardizing procedures are extremely important with walk-in clinics.

The walk-in clinic has been publicized via announcements to patients and other healthcare facilities, the yellow pages, and online.  Dr. Westrom noted that the vast majority of patients who are treated at his urgent dermatology clinic are very polite and appreciative.

 

 

 

Acne: Pathogenesis Revisited

Panelists: James Del Rosso, MD, Alan Shalita, MD, Guy Webster, MD, PhD

For decades the pathogenesis of acne has centered on the formation of the microcomedones as the initiating event followed by an inflammatory cascade. This dogma is now being questioned in a “chicken vs. egg” scenario as being raised as to whether the microcomedone came first or was it precipitated by inflammation that came first.  Data coming out of the lab of Sewon Kang has taken a close look at the issue of what initiates the acne process.  In their work using immunohistochemical and histologic methods, they looked at patients with active acne lesions, normal skin in acne patients and compared them to a control group of people without acne. It was found that in acne patients there appeared a population of inflammatory cells with an absence of neutrophils in the majority of the locations that were evaluated.  This inflammation appeared before the development of hyperkeratinization and microcomedone formation indicating that the microcomedone might not be the initiating lesion. Dr. Kang’s group tracked the development of acne lesions and they found that about three out of ten of the lesions developed into an inflammatory lesion without a visible comedonal lesion.

The take home point is that when looking at an acne patient even normal appearing skin may be harboring inflammation in the follicle that can lead to follicular hyperkeratosis and microcomedone formation so it is important to treat the entire acne prone area proactively and possibly more aggressively.

Case Study

A 33 year-old Asian female presents with a several year history of late onset facial acne and had “clear skin as a teen”.  Her acne has been poorly responsive to treatment with over-the-counter medications as well as topical BPO gel and 0.025% tretinoin cream (“irritates my sensitive skin”) and only modestly response to a 3-month course of oral doxycycline.  She notes some flaring around menses. Her frustration led her to stop all meds and she is not on oral contraception and has two children.

It was noted by the panel that this age group of women have a high level of frustration regarding their acne and several management issues need to be considered including pregnancy.  These “issues” include resistance to the idea of taking oral antibiotics, oral contraceptives and potentially oral medications like spironolactone. Skin sensitivity is also clearly an issue patients such as this one.

Topical Formulations for this Patient Subset

Data for tretinoin 0.05% aqueous gel show that the percent of patients reporting adverse reactions over the 12-week treatment period experienced significantly less incidence of skin related adverse events than with tretinoin microsphere gel 0.1%.

Other topical retinoids available for use with lower potential for cutaneous irritation include Tretinoin Microsphere Gel 0.04%, Adapalene Lotion 0.1%, and Adapalene Gel 0.3%.

Data looking at Clindamycin/Tretinoin 0.025% Gel over one year show that the researchers did see patient improvement increased over time. The percentage of patients with “clear” or “almost clear” skin increased with longer use of CLIN/RA Gel. 57% of patients had “clear” or “almost clear” skin at 12 months. The majority of the patients (78%) were being treated with CLIN/RA Gel as monotherapy; 22% were receiving one or more products (oral antibiotics [12%]; topical therapy [9%]; and isotretinoin [<1%]).

One important consideration is that of P. acnes and antibiotic resistance. Results from a 16-week single-center, double-blind, randomized, parallel-group study of 79 patients with acne who used either a 1% clindamycin/5% BPO gel or clindamycin 1% gel alone show that the combination gel reduced total mean baseline P. acnes count by 99% at week 4, and this was maintained throughout the study. In the clindamycin monotherapy group, the total mean bacterial count was reduced by 87.9% at week 16. Clindamycin-resistant P. acnes counts remained at or below baseline values with the combination gel throughout the treatment while they increased to >1600% of baseline by week 16 with clindamycin monotherapy (P=0.018 vs. combination gel). In addition, drug-resistant, coagulase-negative staphylococci were increased to > 3500% of baseline by week 16. (P<0.001)

A pooled data analysis from pivotal studies stratified by gender looked at male and female patients aged 12 and older with facial acne vulgaris who were randomized to receive either topical dapsone gel (n = 1453; 48% male/52% female) or vehicle gel (n = 1445; 47% male/53% female). The results show that females tended to have better results than males, in both treatment arms. The researchers have not broken the study down by age at this point, nor can they confirm that the results were related to better adherence/compliance.

Hormonal Therapy for Post-teen Acne

Spironolactone is highly effective in post-teenage acne in females. The majority of patients will do well at or below 100mg/day. It is important that clinicians realize that this therapy is highly individualized based upon what dose works best for each patient. Spironolactone can also be used in combination with other topical treatments and oral antibiotics. Safety considerations for oral spironolactone include pregnancy plans and any underlying disorders such as PCOS or endocrinopathies, a risk for hyperkalemia (e.g., use of ACE inhibitors, cardiac disease, diabetes), high intake of K+ containing sports drinks and any significant or potential drug interactions.  There is a question as whether or not clinicians should monitor serum K+ levels. Generally it is not needed, provided there are no risk factors; however, that is the decision of the individual clinician. The general consensus regarding breast cancer history and oral spironolactone is that there does not appear to be a risk; yet, there is no definitive answer about that at this point.

 

Update on Topical Therapies:

The panel discussed vehicle selection, active ingredients, combination regimens, regimens for application/sequencing, and long term data. The major players in the topical therapy playing field today are benzoyl peroxide (BP), retinoids, and clindaymycin (1%). Combination therapy provides incremental improvement and tolerability is based upon selecting products with favorable vehicles.

Can Benzoyl Peroxide reduce comedonal acne lesions?

Yes, and sometimes, markedly.  Sometimes, using BP can give patients a “jump-start” to getting a quicker effect against comedonal lesions.

Is Benzoyl Peroxide 2.5 Enough?

Yes, but it depends largely on the formulation’s ability to deliver the BPO. Combining multiple therapies can provide patients with a faster and greater response. Several studies have demonstrated this benefit.

Studies have shown that Clindamycin has a therapeutic benefit. A thorough literature reviewof five recent studies (N>2000)2 have shown a relative benefit in combination with other agents and it adds to efficacy of benzoyl peroxide/retinoid.

Optimal Oral Antibiotic Use for Acne

Dermatologists prescribe less than 1% of all oral antibiotics, but dermatologists do prescribe 20% of the oral tetracyclines for treating acne and rosacea. Doxycycline and minocycline are the two most commonly prescribed.  Oral antibiotics are used to augment the therapeutic benefit and to speed up the response for moderate -to-severe acne vulgaris, especially for inflammatory lesions. Reduction of P. acnes correlates with therapeutic benefit.

It is important to remember that doxycycline has reported adverse events of serious ulcerations and esophagitis, so it is extremely important to remind your patients to take this medication with large glasses of water and not before reclining. Patient education is key to the therapeutic success of this drug. Minocycline does have a higher risk of drug-induced hypersensitivity however a few cases that have also been reported with doxycycline. Both doxycycline and minocycline have a “grandfathered” approval for acne by the FDA.

 

 

 

 

 

 

 

Drug-Induced SCLE-An Update

Rick Sontheimer, MD

In his presentation, Dr Sontheimer summarized recent observations characterizing drug-induced SCLE (DI-SCLE).  In 1977 he and Jim Gilliam co-authored along with the seminal paper on SCLE.  Dr. Sontheimer suggests that when a physician sees a new SCLE patient it is important to ask whether it is idiopathic SCLE or is this a drug-induced form of the disease.  If the dermatologist can pinpoint the drug causing the condition, an internist or family physician, for example, could stop the drug or prescribe a different drug in a different class of medication, which should result in resolution of the rash and symptoms.

 

The idea that SCLE could be drug-induced was introduced in the mid 1980s in a paper reporting five patients whose otherwise typical Ro/SS-A autoantibody (+) SCLE skin lesions appeared after starting HCTZ & resolved upon discontinuing the HCTZ. Ro/SS-A antibody persisted in all except one patient after SCLE skin lesion resolution and one patient was re-challenged with a thiazide-related diuretic with the reappearance of SCLE skin disease activity that resolved after the initial drug discontinuation.

 

Dr. Sontheimer co-authored a recent paper on the subject of DI-SCLE.   (Lowe, G., et al  A Systematic Review of  Drug-Induced Subacute Subacute Cutaneous Lupus Erythematosus Brit J Dermatol 2010:1365-2133)   Data were abstracted prospectively from 117 articles published up to August 2009.  The authors addressed 8 key questions pertaining to clinical and immunologic issues. They found these patients to be, on average, 15 years older than the typical patients, which, may not actually be all that surprising in that, older patients are more likely to be on more medications. The triggering drug classes are below in Figure 1.

There were marked differences among the various triggering drug classes regarding the length of incubation before the rash/symptoms resulted and time to resolution of the DI-SCLE following cessation of the triggering drug. The cardiovascular drugs seemed to have longest incubation period from 6 months up to 5 years. The anti-fungal drug, terbinafine, had a mean incubation time of 5.1 weeks (29 cases) and 1 case with griseofulvin had an incubation time of 2 weeks. The chemotherapy drugs had an incubation time of days to weeks. It is important to remember that the DI-SCLE didn’t occur in patients until after about 2 weeks and in some cases even longer. The research found that RO/SS-A and La/SS-B antibodies remain present after the resolution of DI-SCLE.

There are several interesting reports on the kinetics of autoimmunity and systemic LE. The Oklahoma Medical Research Foundation conducted a study utilizing the military blood bank. The researchers analyzed antibody levels in blood samples taken prior to the individual developing SLE. Approximately 70% of these individuals, who eventually developed SLE, had RO antibody 5 years prior. The idea here is that there is loss of tolerance to auto-antigens that slowly builds up over time, the autoimmune response matures to a point that it either becomes associated with the development of clinical disease in SLE or these antibodies and their immune complexes are involved in creating the clinical phenomenon.

 

The study also found that histone autoantibodies were, in general, not associated with DI-SCLE unlike drug-induced SLE.  There were no data available to answer whether patients who have experienced DI-SCLE have a subsequent risk for developing idiopathic SLE or Sjogren’s syndrome (SjS). The data were also not available to show the pathogenesis of DI-SCLE. Dr. Sontheimer mentioned that a large number of the drugs recognized to trigger SCLE are photosensitizers known to induce photosensitizing skin reactions without associated lupus-like autoimmunity.

What is the optimal medical management of DI-SCLE? Dermatologists should identify and coordinate with the patient’s internist or FP discontinuation of the triggering drug. It is important to remember that it will probably take 6 to 8 weeks before one can determine whether or not the SCLE was due to a specific drug because it takes that amount of time for the drug to “leave” a patient’s system. DI-SCLE can be treated the same as idiopathic SCLE and clinicians should continue to follow-up on the development of SLE/SjS.

In summary, Dr Sontheimer raises the question of drug-induced SCLE versus drug-precipitated SCLE; he feels it is more the latter. The prognosis for subsequent SLE/SjS development is uncertain and there is a need for a biomarker of drug class triggering SCLE considering the setting of poly-pharmacy and conundrums that clinicians face.

 

 

 

Treatment of Cutaneous LE

The fundamental principles behind the treatment of Cutaneous LE and even Systemic LE have not changed much over the past 50-60 years. Basic principles of sun avoidance/broad spectrum UV protection are mandatory in these patients.   Local treatment may include topical steroids/TCIs.  Systemic therapies are introduced depending on the patient medical status with a stepwise progression from hydroxychloroquine, hydroxychloroquine +chloroquine, chloroquine + quinacrine; retinoids, dapsone, thalidomide; MTX, azathioprine, cyclosporine and mycophenylate.

Management of the “difficult to treat” patient often involves an experimental approach.   According to Dr. Sontheimer, monoclonal antibodies that neutralize class 1 interferon, i.e., interferon-alpha activity have been studied in SLE patients who had skin lesions. They were able to follow the skin while they treated the patients so that they could see clinical improvement in addition to looking at laboratory parameters and skin biopsies. Preliminary data suggests that this approach of modulating the pathologic up-regulation of interferon-alpha in the skin could be of clinical benefit.

Other approaches are currently being explored for various refractory forms of cutaneous LE.  These include TNF-inhibition, phosphodiesterase 4 inhibition, IFN-gamma interfering antibodies and small molecule inhibitors CXCR3 receptors.

In conclusion, it is important that dermatologists have a strong knowledge base of these conditions and an understanding of the optimal approaches to treating the conditions and are aware of some of the recent advances currently being studied.

Filler Complications

Joel Cohen, MD; Director, About Skin Dermatology and DermSurgery; Englewood and Lonetree, Colorado

Dermatologists across the country are using dermal fillers on a daily basis and the products available in the US are believed to be safe and effective provided that they are used correctly. In his presentation, Dr. Joel Cohen discussed the importance of understanding, avoiding and managing dermal filler complications. Filler complications can be stratified into something that doesn’t look very aesthetic when it is superficially or inappropriately placed to situations involving skin necrosis and infection. Regarding aesthetics, Dr. Cohen commented that unfortunately many patients are still walking around with features due to inappropriate use of dermal fillers, which can create an artificial look. This has resulted in patients tending to shy away from using fillers. Dermatologists need to be aware of the agents available and what has been reported as well as different injection techniques.

The key for clinicians, with regards to dermal fillers, is to make things appear natural. Dr. Steve Mandy wrote a review in April 2007 in Dermatological Surgery which reviewed the lip and how important is to place the filler in the right area so that it looks natural.

Injecting the Infra-Orbital Area

Many people prefer different agents to be used in this area and it is important to keep in mind that, in general, this is a very deep injection. If one is to inject superficially, then there is a risk to having the appearance of nodules. There are various hyaluronidase agents available, for example, Vitrase, Amphadase, compounded hyaluronidase, and Hylenex (human hyaluronidase that is currently off the market) . Most of these products are of animal origin, so it is important to do a skin test.

Other issues regarding superficial injection include Artecoll and Artefill. Research has shown that there was not consistency in the particle size of Artecoll; therefore, they were easily ingested which could lead to fibrosis. Some people have had great experiences with Artefill as there is much more consistency in the particle size.

Radiesse (calcium hydroxyappetite) became available in 2003/2004, and many clinicians initially believed that it could be used anywhere.  However, we have learned that it can’t be used in the lips. Sculptra (poly-L-lactic acid) has shown great results as a volumizing dermal filler for the cheeks.  As is the case with all dermal fillers the key to success is knowing how it should be injected.  Careful attention needs to be paid to reconstitution time, volume of injection per location, and the proper injection depth. Sculptra requires longer reconstitution times (at least eight hours prior); higher volume reconstitution, i.e., mix the solution with 5+ cc of sterile water and add 1 cc 1% lidocaine prior to injection; and, inject deeper, i.e., into high fat. It is also important to be careful to avoid injecting precipitate at the end of the syringe. Following these simple points will help in avoiding SQ papules.

Dr. Cohen and others wrote a protocal on the management of visible granulomas following periorbital injection of Poly-L-Lactic Acid in Plastic and Reconstructive Surgery.

Bruising and swelling happens to many patients. It is unfortunate, but it does happen from time to time. There are some things that patients can avoid, such aspirin. Patients on anticoagulants also have to be managed; however, it can be done. There is also a whole list of vitamins that can potentially interfere with bleeding; so again, something to keep in mind.  Clinicians need to be realistic with their patients, so that can expect some bruising and/or swelling which may last up to ten days. It is really important to talk with your patients prior to the procedure.

What can patients do to minimize bruising and what to do when it occurs?

Dr. Kevin Smith wrote an article on the role of ice. Not only will ice decrease pain, it also decreases the bruising and swelling. There are also agents that patients can rub directly onto their skin. Topical Arnica has not proven to be very effective however, oral Arnica may also help regarding swelling and bruising. What is most practical and most helpful solution to resolving bruising quickly in Dr Cohen’s experience is to use a pulsed-dye laser to treat bruising.

Filler Bruising: Treatment with PDL
At 2 days post-filler

  • PDL
  • 7.5 J
  • 6 ms
  • 10 mm spot 1

There is really about a two-day window to treat patients who experience significant bruising. There are also other devices that can be used such as IPL, which is done at short pulse durations (10 ms).

Injection speed is something else that clinicians need to consider.  A clinical trial with Glogau, et al, they found that if healthcare providers inject quickly, it could actually lead to more bruising and swelling (about .3 cc per minute). The study also found that a fan-like injection leads to more bruising and swelling.

Dermatologists need to be aware of potential infection, as it can occur. Treatment includes I & D of the suspected infection, culturing the material, and initiating oral antibiotics.

Necrosis is another important issue to be aware of. There are certain areas that clinicians must pay a particular interest in, e.g. the glabella. It is important to watch the skin as you inject. You should aim superficial and medial, and aspirate. Regarding treatment of a pending area of necrosis if you identify sudden blanching of the skin following injection is to immediately apply warm gauze, repeatedly tap the injected area, apply nitro paste to the treatment site immediately while the patient isin the office and heparin treatment (low MW, SQ). Regarding impending necrosis, hyaluronidase in multiple stabs along and perhaps into the adjacent artery has shown to be a novel treatment. It is very important as a healthcare provider to intervene immediately and not “wait and see what happens” in the cases of impending necrosis.

Sudden blindness has also been reported with different injectable agents around the eyes. Healthcare providers should inject shallow in this area and be extremely careful, keeping the facial arteries in mind.

The risk of sensitivity with the newer agents is extremely low.

In conclusion, clinicians must pay careful attention to the injection site area, take all precautions, and talk to their patients in order to set realist expectations.


  1. Karen JH, Hale EK, Geronemus RG. A simple solution to the common problem Ecchymosis. Arch Dermatol. 2010;146(1):94-95.

Update in the Management of Rosacea

Panelists: James DelRosso, MD; Alan Shalita, MD; Guy Webster, MD, PhD

The diagnosis of rosacea is based upon clinical findings; there are no specific diagnostic tests. The National Rosacea Society Expert Committee on the classification and staging of rosacea has developed provisional diagnostic guidelines for rosacea.1

The guidelines recommend the presence of one or more of the following primary features:

  • Flushing (transient erythema)
  • Non-transient erythema
  • Papules and pustules
  • Telangiectasia

In addition, one or more of the following secondary features often appear with the primary features listed above, although can occur independently in some patients:

  • Burning or stinging
  • Plaque
  • Dry appearance and scale
  • Edema
  • Ocular manifestations
  • Peripheral location
  • Phymatous changes

 

 

 

 

 

Case 1

The panel was presented with the case of a 41 year old white female with a 6-7 year history of waxing/waning facial redness that waxes and wanes and is associated with red bumps and pustules on the nose, cheeks and forehead.  She has “sensitive skin” which is often dry and flaky. Her skin improved on an oral antibiotic for a respiratory infection. She is seeing you to “get rid of the condition”.

It is important to identify the subtype of the disease as that will help dictate the response to treatment. Clinicians should recognize that these patients have increased transepidermal water loss (TEWL) from the central face. Dermatologists need to understand the importance of appropriate skin care in order to address the symptoms and, ultimately reduce the baseline symptoms. Studies have demonstrated that the skin characteristics of patients with rosacea show that about half of the patients scale and become itchy, about one third of the patients experience stinging and burning and these patients do not always have seborrheic dermatitis.

Etiology of Rosacea

The etiology of rosacea is unknown, although research suggests that symptoms are exacerbated by factors that trigger innate immune responses, such as the release of cathelicidin antimicrobial peptides. Studies have shown that patients with rosacea express abnormally high levels of cathelicidin in their facial skin and the proteolytically processed forms of cathelicidin peptides found in rosacea are different from those present in normal individuals. These cathelicidin peptides are a result of a post-translational processing abnormality associated with an increase in stratum corneum tryptic enzyme in the epidermis.2

Therapeutic Options: Topical Agents for the Treatment of Rosacea

 Metronidazole works through the inhibition of ROS generation from neutrophils. Azelaic Acid also works through the inhibition of ROS generation from neutrophils. Azelaic Acid also has decreased KLK-5 activity (serine protease activity); therefore,  decreasing the cathelicidin. It also downregulates the Toll-like receptor 2 (TLR2), similar to topical retinoids.

Retinoids also have a variety of ways in which they can modulate the disease, for instance they work through the inhibition of ROS generation from neutrophils and also have the downregulation of TLR2 and modulation of MMP activities, i.e., repair of dermal matrix degradation.

The tetracycline derivatives have a variety of down-regulating properties that appear to help with rosacea. They reduce inflammatory cytokines: IL-1b, IL-6, and TNF-1-a. They inhibit the serine protease activation of catheclicidin. They inhibit MMPs collagenase-8, -13, gelatinase -2, -9, elastase -12 and pro MMP activation and protect TIMP. Tetracyclines also inhibit nitric oxide activity and the arachidonic acid pathway.

Data on minocycline show the suppression of serene protease activity. Specifically, when patients were on minocylcine, the serene protease activity decreased, when they stopped it increased, and when they went back on the minocycline, it again decreased. (Yamasaki et al. Nature Medicine (2007) Aug 13 (8) 975-80)

As far as oral therapies for the treatment of rosacea, the tetracyclines are used; however, they are not FDA approved and there is reason to believe that dermatologists only need to use the subantimicrobial doses in order to garner the anti-inflammatory effect. These doses have widespread use and years of clinical experience. There are multiple pharmacokinetic and microbiologic studies. They are FDA-approved with large pivotal trials. Data exists with regards to the combination with topical therapy. Their efficacy is comparable to doxycycline 100 mg daily and there are potential safety advantages.

With the use of doxycycline (40mg Extended Release, QD) once can see demonstrated efficacy in papulopustular rosacea, there is a lack of antibiotic effect, efficacy is the same as that of doxycycline 100mg/QD, and there is a favorable safety profile. One 12-week study looking at doxycycline 40mg demonstrated that by week 4, close to half of the patients achieved clear or near-clear skin and by week 12, about 75% of the patients achieved clear or near-clear skin. The data were similar to that of patients utilizing add-on therapy in addition to doxycycline.

In conclusion, healthcare providers should be aware that there are a lot of data that show the efficacy of these agents for the management of papulopustular rosacea.

When comparing doxycycline 100mg to doxycycline 40mg, the effects were essentially the same based on one trial. Patients do not need to be exposed to changing their bacterial flora unnecessarily by starting with this treatment first, and; therefore, patients are not exposed at an antibiotic effect.

Case 2

The second case presented to the panel was a 42 year-old White female presents with a 7 year history of central facial (nose/malar eminences/chin) redness which waxed and waned in intensity over the years but is now persistently red There is central facial predominance.  She does not relate ever having any “red bumps” or “pus bumps” developing on her face, including during flares.  She has “sensitive skin”. She occasionally complains of itching and burning. She is interested in the correct diagnosis and treatment. Her health history is unremarkable otherwise.

Medical Treatments for the Redness of Rosacea

Erthematotalngiectatic rosacea (ETR) is more common than papulopustular rosacea. Available therapies include topical agents, such as metronidazole, azelaic acid, and oral agents such as the tetracyclines all of which improve primarily perilesional erythema. These products can occasionally help patients with their rosacea, but the background redness type does not always respond very well.  The critical issue is the presence of persistent telangiectatic mats in the affected areas.  The telangiectasias can be reduced when treated with laser/light devices.  Topical vasoconstrictors that can be used to reduce erythema (Oxymetazoline and Brimonidine) are in clinical trials and have shown excellent clincial responses during these clinical trials.

 

References:

1. Wilkin, J, Dahl, M, Detmar, M, et al. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol 2002; 46:584.

2. Yamasaki K, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. 2007. Nat Med;13(8)975-980.

 

 

Non-invasive Fat Removal and Tissue Tightening: What’s the Truth?

Mathew M. Avram, MD, JD

Non-invasive Fat Removal

This is a technique with limited, but real efficacy. It is important that Dermatologists critically assess these technologies in this emerging field. There are many different technologies for fat removal, the first of which is Focused Ultra Sound, known commercially as “Ultra Shape”.  This is mechanical, non-thermal energy. It is currently not FDA approved.  The initial study looked at 30 patients treated at 3 monthly sessions. The researchers did bilateral treatments, with no control, of thighs, abdomen, and flanks and achieved a circumference reduction of 2-3 cms.  LFTs, lipids, & liver ultrasound showed no adverse systemic effects and there were similar findings in a subsequent study.  The problem that clinicians face is that there was no untreated control so it is difficult to ascertain the true degree of efficacy.  Circumference, when subject to mathematical analysis, is an inherently imprecise measure of improvement.  MRI could provide a more objective improvement; however, it was performed in this study.

A subsequent study in Hong Kong using this device treated 51 subjects, with 3 monthly treatments. They didn’t see any significant change in ultrasound, circumference or caliper measurements and it resulted in poor patient satisfaction.

High-Intensity Focused Ultrasound is commercially known as Lipo Sonix, was recently FDA-cleared. This features rapid heating of adipocytes producing coagulative necrosis and cell death in adipose tissue.  There is a published retrospective study that looked at 85 patients with1 treatment session. On average a 4.6 cm decrease in waist circumference was seen after 3 months and lipids, LFTs, and CBC were within normal limits. Temporary adverse effects in 11.8% of patients (4-12 weeks) included prolonged tenderness, ecchymosis, nodules, edema, and procedural pain in one patient that required discontinuing the procedure. Unfortunately, this was not an ideal study because it was retrospective and diet was not controlled. Dr Avram felt that this, in fact, undermines the findings of the study.

In a recent poster presentation, diet was controlled and there was a statistically significant circumference improvement at 12 weeks in treated patients versus sham patients. Yet, it was unclear how circumference measurement was validated.

Adverse events were more common than in the published study and included procedural pain in 90% of patients, post-treatment pain in 57%, bruising in 66%, and swelling in 9%.

Monopolar radiofrequency has been shown to produce lipoatrophy in some patients and is still awaiting clinical studies. Bipolar radiofrequency which is combined with infrared light and vacuum massage, is FDA approved; however, its efficacy is yet to be determined.

Low level light therapy (LLLT), which is, FDA-cleared, is a multiple head low-level diode laser at 635 nm. An LLLT study (blinded bi-lateral treatments) looked at 59 patients who received three treatments per week for 2 weeks some improvement was reported however, at a minimum, further study is needed.  There were no data of efficacy more than 2 weeks out. There were no data on ultrasound or other non-invasive evidence of decreased fat layer and no histology.

Cryolipolysis is a technique that was developed at Massachusetts General Hospital and is FDA-approved for non-invasive fat removal.

Cryolipolysis is the non-invasive cooling of fat to selectively cause fat cell death without damage to surrounding tissue types. It is based on the concept of the clinical phenomenon of “popsicle panniculitis”.  The mechanism of action involves the selective crystallization of lipids in fat cells at temperatures above freezing. This results in apoptotic fat cell death followed by slow dissolution of cells and gradual release of lipids; therefore, causing an inflammatory process resulting in fat layer reduction over 2-3 months. After the animal studies, there was a human study where 32 subjects in the “love handle” group were analyzed. One side was treated and there was a contra-lateral side untreated control. The parameters ranged from CIF 33 (-64 mW/cm2) for 60 minutes to CIF 42 (-72 mW/cm2) for 45 minute. The researchers evaluated efficacy 4 months post-treatment utilizing visual assessment as primary a endpoint, as well as ultrasound and histology. Ultrasound showed a   22.7% decrease in fat layer thickness. Post-procedure side effects included redness that lasted for a few minutes to a few hours, bruising and temporary dulling of sensation in treated area. There were no changes in pigmentation and type VI skin types have been successfully treated.  No laboratory abnormalities were detected. A  rare side effect (1 in 1,500) is the report of significant pain lasting about 2 weeks and resolves without sequelae. The mechanism for this side effect is unknown.

Treated and Control Side

In conclusion, the data regarding cryolipolysis (Zeltiq) indicates clear, but limited non-invasive fat removal. It not a replacement for liposuction and is not a weight loss device. It is best suited for local fat removal resistant to exercise in relatively fit patients. The best areas to treat are the love handles and lower abdomen. It is important that clinicians recognize that patient selection is crucial.

We can see that non-invasive fat removal is here. It cannot be compared to liposuction. There are several different technologies presently available. Proper patient selection is important as some devices work, and others do not.

Tissue Tightening

Many different technologies exist for tissue tightening.  They all attempt to tighten skin laxity by the deposition of heat.

The temperature-related effects will differ depending on the amount of heating that one chooses to perform:

42-52 ºC reversible injury, heat shock
> ~52 ºC cell apoptosis, necrosis
> ~68 ºC type I collagen denaturation
> ~100 ºC vaporization

The mechanism of action  is tissue contraction; therefore, each device produces heating of the dermis in order to cause significant shortening of collagen structures.  The devices also want to achieve a secondary wound healing response with collagen deposition. This has been demonstrated using monopolar radiofrequency (Thermage technology) using animal histology.

Tissue Tightening Technologies

The good news is that these technologies can achieve a certain degree of tissue tightening and they are continuing to improve and, for the most part, they are rather safe. The bad news is that the results can be unpredictable and in many cases are not seen. Each patient has to be looked at individually and they must realize that the results can take months before they are actually manifested. These treatments can often be painful and quite expensive and many times patients may require multiple treatments. It is important that physicians counsel patients and give them a proper sense of potential results.

Ablative Fractional Resurfacing

Ablative fractional resurfacing can produce some modest tissue tightening.  However it is very important to resist the temptation to be aggressive in order to maximize the clinical benefit.  Hypertrophic scarring of the neck has been reported with ablative fractional resurfacing.  (Avram MM, Tope WD, Yu T, Szachowicz E, Nelson JS. Hypertrophic scarring of the neck following ablative fractional carbon dioxide laserresurfacing. Lasers Surg Med. 2009 Mar;41(3):185-8.)

Radiofrequency

There are monoploar, bipolar and fractional bipolar radiofrequency devices. The mechanism of action of monopolar radiofrequency devices is that the current runs through the dermis but does not conduct well in the fat however it conducts along the septae in the fat causing heating of the septae and surrounding fatty tissue. Monopolar radiofrequency devices that are combined with a superficial radial cooling component (Thermage device) allows the user to change cooling and heating parameters to deliver heat to the deeper tissue in a given targeted area while protecting the epidermis with the cooling system. There is also no patient recovery time. It often takes up to 3-6 months to see the results.

Biopolar radiofrequency consists of two electrodes.  The heat runs between them and many of these devices are coupled with a suction device to maximize the tissue between the electrodes allowing clinicians to achieve deeper penetration. It may provide a mild benefit for tissue tightening.

Fractional bipolar radiofrequency utilizes a fractional pattern of bipolar RF heating that is delivered by a micro-needle electrode array directly into the deep dermis .It provides real time dermal temperature monitoring.  The treatment is painful and requires significant anesthesia.  However, its efficacy is yet to be determined.

Focused ultrasound (US) allows for deep, non-invasive treatment at any tissue depth. US can treat far below the dermis.  Treatments are guided by real time imaging.  The key to success and avoiding complications is to target carefully using imaging to guide the treatment of the skin and SMAS.  It is important to remember that one should avoid targeting any arteries or nerves.  It has great potential for not only targeting tissue for aesthetic purposes but for other medical therapies.

Skin Imaging Slide

Skin Imaging

Issues around US include clinical questions regarding pattern, depth, density and the number of necessary treatments. US looks like a promising technology; yet, its efficacy still requires more proven results.

Its important to remember that there are limits to tissue tightening technologies. It is important to discuss these issues with patients and consider that the current treatment paradigm may need to be approached in a different manner. Perhaps dermatologists need to consider restoring elasticity, rather than tightening. We do know that tissue tightening can improve non-invasive skin elasticity, the results are unpredictable, this should not be looked at like a face-lift and patient education and communication is key its the success.

Psoriasis Update 2011: Psoriatic Arthritis (PsA)

Arthur Kavanaugh, MD

In this presentation, Dr Arthur Kavanaugh, of UCSD, discusses the newest concepts in the management and treatment of patients with psoriatic arthritis (PsA).

A major question still exists among healthcare professionals…Is methotrexate (MTX) effective among our PsA patients? Dr Kavanaugh states that in a room full of Rheumatologists, everyone would agree that MTX is effective; however, the data doesn’t necessarily indicate its effectiveness, as it is somewhat lacking.

For more information on the history and data around MTX, Dr Theodore Pincus recently published a study in Clinical and Experimental Rheumatology focusing on the use of MTX in various disease states, including skin disease and PsA.

There are very few studies utilizing MTX in psoriatic arthritis and little support for its use in PsA patients. There were a total of 4 double-blind, placebo-controlled randomized clinical trials in the published literature.

There is not a lot of support for MTX in patients with active PsA. A number of studies utilized higher doses of MTX; therefore, we can see a dose effect, (patients taking over 15mg/week of MTX) in patients with psoriatic arthritis, which shows that there is some benefit to its use.

The MIPA study, a 6-month, double-blind placebo-controlled trial, was based out of the UK. The entry criteria required one swollen joint. The researchers were able to recruit only 221 patients over the course of eight years.  There were lots of drop-outs and in conclusion the results were questionable as to the value of MTX in patients with active PsA. There are a few issues with this study and the researchers reported that healthcare providers need to see the full data and the question still remains:  is the 15mg dose of MTX really effective?

Dr Kavanaugh recently participated in a PsA panel that was organized through EULAR (European League Against Rheumatism), with the intent to develop guidelines for the management of PsA. The panel concluded that patients with active PsA should be on MTX before one would be given a biologic. This recommendation would be questionable to many US dermatologists, and, in turn, the EULAR panel did revise their statement to allow for patients in “exceptional” cases to be started on a biologic.  It is really up to the clinician and patient to decide on the appropriate therapy based upon the data, quality of life, benefits and risks.

Data do exist around the efficacy of TNF inhibitors plus MTX in Rheumatoid Arthritis patients; yet, the data are limited in patients with PsA.  A systematic review of the TNF inhibitors demonstrated a risk ratio response of about 11 for an ACR 50 and a risk ratio of 17 for a PASI 75.

Is there synergy when utilizing MTX plus a TNF inhibitor in PsA? It is known in Rheumatoid Arthritis patients, yet it is unknown among our PsA patients.

The RESPOND study compared MTX (15mg/week) to INF (5mg/kg)+ MTX (15mg/week) and showed that the patients in combination did better than those on MTX alone.

Assessing Psoriatic Arthritis

When assessing PsA, it is imperative that healthcare providers look at each patient individually. It is important to consider peripheral arthritis, and look at swollen joints and the composite scores; clinicians need to consider axial arthritis, quality of life, radiographs, skin disease and other issues such as dactylitis (swelling of the entire digit) and enthesitis.

The CPDAI (Clinical Psoriatic Disease Activity Index) is a new instrument for disease activity and various clinical domains of PsA. This has been borrowed from the GRAPPA group, and broken into its individual domains. When we have these tools, we can then begin discussing remission. It’s important to consider all of the different facets of this disease (skin, joints, spine dactylitis, etc…) The important thing to consider regarding patient management is that each patient has to be looked at individually, as it is not an algorithmic treatment/management strategy.

Video: Treatment Options for AKs

The Science of Aging Skin

Michael Gold, MD

How do we look at all of the skincare products available? What does it mean to our patients? It is important that clinicians recognize what drugs and therapies work for dermal aging. Sunscreens, i.e., those with UVA and UVB protection, can prevent melanin production and collagen and elastin degradation. Dermatologists need to be aware of what ingredients are in these various sunscreens. Retinoids have also changed the management paradigm of aging skin showing a clinical improvement in skin texture, wrinkles, and pigmentation. Hydroquinone is probably the most effective inhibitor of melanogenesis. It exerts its depigmenting effect by selective action on melanocyte metabolism which results in more even skin tone and reversal of abnormal pigmentation. Hydroquinone helps prevent/reduce PIH and has been proven safe and effective by the FDA for over forty-five years. Many clinicians use hydroquinone in conjunction with retinoids.

Because of the increasing aging population, there as been a consumer demand for anti-aging products. The average patient is 30 to 55 years old and well educated. Because of the number of products available, there is also a lot of confusion around choosing what products would be the most efficacious and safe.

What is a Cosmeceutical?

According to Dr Al Kligman, the physician who termed this word, it is “something between a cosmetic and pharmaceutical”. They are topical cosmetic products that exert a pharmaceutical, but not necessarily a biologic, therapeutic benefit. Their use is mainly for anti-aging purposes, designed to improve the appearance of lines and wrinkles, skin discoloration and other defects.

How do we evaluate these various compounds? Healthcare providers know that a biologically sound rationale exists for their cutaneous effect. The therapeutic concentration range of the ingredient is known, the formulation science stabilizes the ingredient in the product, and the trans-stratum corneum delivery science for the ingredient is incorporated into the formulation. However, we need more clinical blinded trials conducted by third-party companies in order to better represent the data, as clinicians want to see patient satisfaction.

What Cosmeceuticals Exist?

Pierre Fabre

Pierre Fabre has a water-based dermocosmeceutical that hydrates the skin and has many uses as a moisturizer and anti-inflammatory agent. One of the company’s products, Retrinal™, comes in three doses for hypersensitive skin and the eye area, all skin types, and intensive skin rejuvenation. Clinical studies show that these retinoid products, which can be purchased OTC, are as effective as prescription retinoids. Another one of their products, Gel d’eau Thermale, is a water-based gel that can be used in post-laser procedures such as laser hair removal and has an immediate cooling effect, and analgesic effect, and a soothing, anti-inflammatory effect. Pierre Fabre also has positive data around its product Avene Thermal Spray Water. Glytone, a vitaceutical facial serum, provides all day anti-oxident protection through its continuous release of free Detla-Tocopheryl. Six month studies on photodamaged skin showed efficacy.

Recently, the European Journal of Dermatology published a series of peer-reviewed papers showing the clinical efficacy of these water-based products in in photoaged skin as well as disease states such as eczema and psoriasis.

Neocutis

Neocutis has many products using multiple fetal fibroblast cell lysates. Several papers have been published discussing how this novel human growth factor and cytokine skin cream and improve skin surface topography of aged facial skin.

Blanche

Blanche Skin Lightening Cream with Melaplex represents a novel and first time approach to target the pathway of melanin formation at multiple levels. Blanche contains a prescription strength Hydroquinone (4%) for effective skin lightening when used with Melaplex, which is a unique skin-brightening complex that is used to restore the youthful appearance of even skin tone. In a head to head study Blanche produced equivalent results to Triluma in the treatment of dyspigmentation.

Perle

Perle is a Skin Brightening Cream with Melaplex. Many clinicians do not like to utilize hydroquinone, and some of these newer products, such as Perle, are well-tolerated and hydroquinone-free. A 45% reduction in pigment was found after a 12 week study protocol. Many clinicians have used hydroquinone products for 12 weeks and then switch to hydroquinone-free products. The advantage of this product is that there is no restriction on how long you can use this product and it can be used safely in pregnancy.

Both of these products have enabled clinicians to help block the pathway of melanin formation.

Syneron

Elure, which is a skin-lightening product, is based on Melanozyme containing lignin peroxidase (LIP). LIP is a naturally occurring enzyme deriving from a tree fungus. For many years, LIP has been identified as the enzyme that breaks down lignin in decaying trees, causing rapid decolorization. Because the molecular structure of lignin is similar to that of melanin, recent research confirmed that LIP also has the potential to improve the appearance of skin by reducing eumelanin. Data suggest that Elure is significantly more efficient that 2% hydroquinone.

Looking ahead, Dr Gold stated: “In 2011 pigment will be the new wrinkle.”

Biopele Growth Factors (GFs)

GFs work as chemical messengers between cells to turn on or off specific cellular activities. They can be derived from a number of sources, including epidermal cells, placental cells, colostrum and plants. GFs promote fibroblast and keratinocyte proliferation and induce extracellular matrix formation. SCA Biorepair technology (Tensage) is a novel fibroblast growth factor. Secretion of the snail Cryptomphalus aspersa (SCA) is an active, glycosaminoglycan secretion generated by the snail during times of stress such as exposure to radiation, burns, etc. SCA is shown to repair the snail’s skin in as little as 48 hours and eliminates concern expressed over VEGFs. Data suggest that this product shows marked improvement in skin texture and moisture, enhanced collagen deposition, increased hyaluronic acid content and a reduction in solar elastosis.

Biopele also makes non-prescription retinoids to counteract the effects of photoaging.

It is important that dermatologists realize that we now have the opportunity to change the function of skin. Cosmeceuticals are showing a great improvement in this ability.

Obagi

ELASTIderm is a topical eye treatment that is clinically proven to show increased elasticity and a reduction in visible wrinkles.

Obagi’s Nu-Derm System is an OTC product designed to be used in conjunction with a prescription retinoid to transform damaged skin cell functions in order to reverse photoaging. The data suggest that Nu-Derm System demonstrates a superior efficacy at 2 weeks as compared to other therapies.

The 4-step Obagi hydroquinone/tretinoin-based skin care system helps to correct premature skin damage, reduce future skin damage. Care in customizing the system to the individual is important. The sequence of application of component products is:

  1. Skin preparation (cleanser + toner)
  2. Skin correction (4% hydroquinone + exfoliant)
  3. Skin stimulation (4% hydroquinone + 0.05% or 0.1% tretinoin)
  4. Skin protection (sunscreen)

The published data suggests that there are benefits of using a hydroquinone/tretinoin skin care system for patients particularly when used in conjunction with light based devices such as IPL.

Coffeeberry

CoffeeBerry® is the fruit from the coffee plant (Coffea arabica), from which the commonly known coffee bean is derived. When harvested at a sub-ripe growth stage, the flesh of the CoffeeBerry® fruit is at peak antioxidant concentration. RevaleSkin utilizes coffeeberry and has shown a decrease in the appearance of fine lines and wrinkles.

Priori Skincare

Priori now has their own coffeeberry line, the Priori Coffeeberry Natureceutials with all of their products designed to improve skin renewal and decrease fine lines and wrinkles. Idebenone is another product of Priori’s, again showing a reduction in pigmentation and rosacea.

Allergan

Allergan’s product, Vivite, which combines glycolics and antioxidants, has shown improvement in the appearance of fine lines/wrinkles, skin roughness and hyperpigmentation after 8 weeks of treatment.

LATISSE®

LATISSE® is the first and only FDA approved therapy for the treatment of hypotrichosis of the eyelashes. LATISSE works by increasing eyelash growth including length, thickness, and darkness. The exact mechanism of action for LASTISSE® is unknown. LATISSE® solution is a structural prostaglandin analog that exerts its action by selectively mimicking the effects of naturally occurring prostamides. The physiochemical properties of LATISSE® solution favor its effective skin absorption into the dermis where the hair follicles reside.

LATISSE® is associated with enhanced eyelash growth and most subjects in clinical trials noticed favorable changes in their eyelashes.

NIA24

The NIA company uses a Pro-drug system that turns into an active within the skin. The company utilizes iacin in order to improve skin function. Pro-Niacin has shown to dramatically strengthen the skin barrier, improve cell turnover/differentiation, improve moisture retention and increase sun protection. Its visible improvements include increased smoothness and firmness, improved texture and tone, reductions in the appearance of fine lines and wrinkles and improvements in chin and jaw firmness.

Skin Medica

TNS is another Growth Factor. Its work has been verified time and time again, by seeing improvement in fine lines and skin elasticity. TNS is unique for several reasons: patented advanced manufacturing process; physiologically balanced growth factor mixture; stability of a high concentration of growth factors; proven safety of growth factors over time.

Clinical studies have demonstrated the efficacy of TNS and it has an excellent safety profile with over 7 years of use.

Recently, SkinMedica has come out with TNS Essential Serum that is both a Recovery Complex (same TNS) and a Corrective Complex. It is an interesting synergy of the products and several independent studies have verified its effectiveness in skin texture roughness, peri-ocular wrinkles, smoothness and skin tone.

SkinMedica also makes a variety of antioxidants and retinoids. In comparator studies the Tri-Retinol performed as well as tretinoin .025% in the treatment of photoaging but with less irritation.

Anti-redness Products

According to Dr. Gold, in addition to pigment disorders, another “huge” area being targeted by the cosmeceutical companies is redness. There are lots of reasons that patients become red in their skin. Some of the most common reasons are blushing, acute redness/flushing, which can be due to sun exposure, cosmetic procedures or drug-induced as well as chronic redness associated with skin disorders such as acne, rosacea or atopic dermatitis. Most of the products being developed in this space target prostaglandin E2 (PGE2) that is a bioactive molecule in the prostanoid family of lipids responsible for vasodilation. It is elevated by a number of stimuli including UV exposure, chemical exposure, neuronal and hormonal stimuli and inflammatory skin conditions such as rosacea.

CalmPlex is a novel product containing patented ingredients and has shown its effect on skin redness. Most cosmetic products hide redness or temporarily reduce blood flow to the skin using vasoconstrictors. However, CalmPlex prevents UV and chemical induced release of inflammatory mediators, especially PGE2. Several studies have shown its effectiveness in reducing skin redness.

Summary

It is important to know what products your patients are already using at home to avoid patient confusion. Patient education and staff education are keys to the success of these products and patient satisfaction. Aestheticians must spend a lot of time with patients going over their regimens in order to achieve success. Taking lots of before/after photographs can help your patients, build confidence and trust and it serves as a nice cross-referral.

Evolving Landscape of Therapeutics for Actinic Keratoses (AKs)

George Martin, MD

George Martin, MD

Watch video of Dr. Martin’s full talk

At the podium during Maui Derm 2011, I discussed the evolving landscape of therapeutics for actinic keratoses (AKs).  In the US nearly 60% of “at risk” individuals over the age of 40 have at least 1 AK.  Therapy for AKs has resulted in over 5 million office visits with an estimated healthcare burden of over 1 billion dollars.

As healthcare initiatives examine and reward patient therapeutic “outcomes”, the clear lack of efficacy of cryosurgery as a “field therapy” for patients with numerous AKs will cause a shift in therapeutic algorithms toward field therapies.  However; field therapies, when performed according to the package insert, are associated with prolonged side effects that dramatically affect patient compliance.  As a result, small investigator initiated studies examining short course, combination and interval therapy in efforts to enhance patient compliance while maintaining efficacy are becoming more prevalent in the literature. Additionally new drugs such as the plant derived ingenol mebutate gel are ready to be brought to the marketplace and new formulations of existing drugs such as imiquimod 3.75%, which employs a more “user friendly” protocol compared to 16 weeks of twice daily 5% imiquimod, have been introduced.

I presented the work of Prof. Eggert Stockfleth of Charite Hospital in Berlin who has published compelling molecular data on the role of human papilloma virus (HPV) 21 as a co-carcinogen along with UV.  The role of HPV 21 is analogous to the role of certain oncogenic HPV sub-types in cervical cancer.  HPV 21 has been found in 95% of AKs and 100% of cutaneous SCCs in Prof. Stockfleth’s study. Tumour-inducing effects of HPV 21 have been attributed to its production the viral protein E6.  E6 interacts with pro-apoptotic Bak-protein and the p53 protein resulting in inhibition of apoptosis.   A vaccine directed against the HPV 21 is in early stages of development. Because of the increased risk of SCC development in organ transplant patients  (>20x the rate of SCC development compared to non-immunocompromised individuals) the efficacy of pre-operative immunization in preventing AKs and SCC in this high-risk group will be studied first.

Figure 1: Fluorokinetic Analysis

Figure 1: Fluorokinetic Analysis

ALA PDT has come a long way from its lengthy 14 – 18 hr. incubation times in efforts to become user friendly.  However, I presented data that the shorter 1-hour ALA incubation times may have sacrificed significant efficacy for convenience.  Based on fluorokinetic data on the accumulation of the photosensitizer protoporphyrin IX (PpIX) inside AKs following ALA application (Figure 1) and patient observation, we now regularly treat patients using a minimum of 3-hour ALA incubation period to allow more PpIX accumulation inside AKs.  In patients with “stubborn” AKs we pre-treat with 5-FU daily for 7 days on the face and 10 days on the scalp and extremities followed by PDT using 1 – 3 hour incubations.  Lastly, for the patient with extensive AKs on the face and scalp who I never seem to get close to clearing, pretreating with 3.75% imiquimod for 1 week followed by ALA PDT using a 3 hour incubation has produced remarkable sustained clearance not achieved in either ALA PDT alone or in combination with 5-FU.

Figure 2: Therapeutic "Downtime"

Figure 2: Therapeutic “Downtime”

I addressed the issue of pharmaco-economics involving our currently available field therapies.   Medicare insurance covers the cost of ALA PDT, which is a decision factor for cash strapped seniors unable to afford the several hundreds of dollars for topical field therapies.   In terms of downtime for working individuals, ALA PDT affords the least amount of downtime (generally 1 week) compared to other field therapies (Figure 2).

5-FU remains a cornerstone of  field therapy in most our practices.  I was noted that phase III data on 0.5% 5-FU showed that 1 week of daily use of 0.5% 5-FU cleared nearly 75% of individual AKs.    I think that it is time that we should re-examine the scorched earth policy of 4-week 5-FU therapy!

Figure 3:  AK of the Lip

Figure 3: AK of the Lip

What’s been overlooked for actinic chelitis?   3% diclofenac gel applied twice daily for 3 months is particularly effective for this problem. It is very tolerated and results in excellent clearance data with over 80% of individual lesions clearing and patient satisfaction was rated as very high.  (Figure 3) For those patients not wishing at least 2 weeks of downtime following any of the current modalities ranging from PDT, CO2 laser resurfacing, 5-FU or imiquimod this is a tolerable option that allows people to continue socializing.  Recent data on 3% diclofenac has shown significant long-term clearance during the phase IV study involving 1-year follow-up evaluations.

The evolution of imiquimod therapy for the treatment of AKs has undergone an evolution since the introduction of 5% imiquimod applied twice weekly for 16 weeks.  While the efficacy of this regimen is significant, the tolerability and patient compliance is wanting.  In Europe the use of 5% imiquimod 3-times weekly 4 weeks followed by a 4-week rest period and repeated produces excellent clinical and histologic clearance long term (1 year) clearance but is once again associated with significant patient downtime.  Limiting therapy to only 4 weeks results in only <30% clearance compared to two cycles that result in approximately an 85% clearance.  The introduction of 3.75% imiquimod applied daily for 2 weeks-2 weeks off- 2 weeks on has resulted in better patient tolerance and impressive individual lesion clearance (>80%). Long-term complete clearance (1 year) data for those phase III study patients initially completely clearing was 40%. In light of the role of HPV 21 as a co-carcinogen responsible for the development of AKs and cutaneous SCCs, the use of imiquimod as an immune modulator used either alone or in combination would seem to have a therapeutic advantage.

Finally, ingenol mebutate 0.015% gel when applied for 3 consecutive days during phase III studies, produced very nice and consistent clearance data (80% range) as a field therapy for the head area (face and scalp).  The 3-day topical therapy had excellent patient compliance, which is a major challenge for other field therapies.  Downtime following ingenol mebutate was on average 2 weeks.  It will be interesting to see how this drug will be used as a field therapy because of the inability to “titrate” its response following application.  Likely most of us will begin using it a “limited area” field therapy. However the future seems very bright for this latest pending addition to our therapeutic toolbox.