Psoriasis Update: Part 3

Comorbidities and Cardiovascular Status of Psoriasis Patients

Craig Leonardi, MD

In this final session of the psoriasis discussion, Dr Leonardi discussed co-morbidities and the cardiovascular status of patients with psoriasis.

Metabolic Syndrome and Psoriasis

Psoriasis patients are at an increased risk for the metabolic syndrome. There are meta-analyses that have been performed that have shown that these patients have an increased risk for type 2 diabetes, hyperlipidemia, hypertension, and obesity.

Myocardial Infarction (MI) in Patients with Psoriasis

Joel Gelfand and colleagues conducted a cohort study of 130,976 to determine the risk of MI in psoriasis patients. The results showed that patients with severe psoriasis had a marked increase of MI as compared to those patients with mild disease.

Why do psoriasis patients have increased cardiovascular risks?
  • The use of dyslipidemic therapies, such as corticosteroids, acitretin, and cyclosporine
  • The increased prevalence of associated and/or independent risk factors: smoking, obesity, hypertension, and alcohol misuse
  • Uncontrolled inflammation leading to endothelial dysfunction and dyslipidemia
Does the treatment of a chronic inflammatory disease reduce cardiovascular risk?

A retrospective cohort study demonstrated that the use of methotrexate reduces the incidence of cardiovascular disease in patients with psoriasis. It is also shown that treatment with TNF blockers decreases the mortality risk in patients with rheumatoid arthritis. In psoriasis, TNF-inhibitor treated patients had a 48 percent reduction of MI risk.

What about CV risk in the setting of IL 12/23 inhibition?

Briakinumab’s Phase III demonstrated an increased number of CV events ( 5 compared to 0 in placebo) and MACE signals were also seen in the ustekinumab phase III trial as well.

Association between biologic therapies for chronic plaque psoriasis and cardiovascular events- a meta-analysis

This study looked at 19 high quality studies. In the TNF studies, only two MACE events were reported (one in treated/one in untreated). In the 12/23 inhibitors, there were 10 events compared to 1 in placebo. Statistics show that the TNF antagonists are not associated with MACE.

In the JAMA article that was published, the conclusions (above) had to be tempered. Tzellos et al re-looked at the data and published a re-analysis of the data using different statistical modeling (they used the PETO method), they found no increased risk of MACE events.

Risk of MACE in IL 12/23 Psoriasis Trials
  • Background rate of MACE 0.0012/pt-yr, which was based on the aggregated rate in the placebo group for all 22 studies.
  • Rate in the IL-12/23 studies was 0.012 (10 times the background rate)
What are some of the next steps that need to be taken?
  1. Pay attention to the issue
  2. Emerging therapies-need to wait for phase III data (blocking 12/23 downstream)
  3. Pay attention to Amgen’s development efforts on brodalumab in which brodalumab and ustekinumab are involved in a comparator trial
  4. PSOLAR (Janssen registry) may provide data
Final Comments

American Academy of Dermatology Guidelines Recommends Monitoring; Basic CV screening includes:

Laboratory evaluation

  • Fasting comprehensive metabolic panel
  • Fasting lipids
  • Blood pressure
  • Assessment of overweight/obese status

Inquiry

  • Alcohol
  • Smoking
  • Depression
  • Arthritis

Ustekinumab: recommendations for use

  • Consider all options when selecting a biologic
  • Know that psoriasis pts typically have multiple cardiac risk factors
  • Consider starting with low (45mg) dose regardless of patient weight
  • Consider adding ASA 81mg QD
  • Await further analysis (FDA, EMA, Abbott, Janssen, Amgen)
  • Remember that all new drugs are ‘new’

Consider additional specialty care for psoriasis patients

 

Psoriasis Update: Part 2

Pipeline Psoriatic Arthritis Therapies that Have Efficacy in Psoriasis

Arthur Kavanaugh, MD

There are many potential therapies currently under development for the treatment of psoriatic arthritis (PsA) and appear to fall under two categories: biologic agents and oral agents (kinase/enzyme inhibitors).

Th Cell Development

Th17 cells are elevated in PsA patients. One of the exciting areas of research now is that of additional subsets of Th cells. This is leading to the development of new products in the pipeline for inflammatory diseases such as PsA.

Ustekinumab in PsA

This data was just presented a few months ago at the American College of Rheumatology looking at ACR scores and PASI scores both of which demonstrated improved response versus placebo.  It is important to keep in mind the effect of weight therapeutic response as heavier patients experience a lower response in therapy. Obesity seems to be very pro-inflammatory and it effects how people are responding to their current therapies.

What do we do with patients who have been on TNF inhibitors already and are not responding?

This group of patients is tough and demonstrates the need for more research.

Emerging Molecules Under Development for Psoriatic Arthritis
  • Secukinumab (IL-17a receptor)
  • Abatacept- (T cell inhibitor)-in PsA, you don’t see a great response, particularly in those who have been previously exposed to a TNF inhibitor
  • Tofacitinib-quite effective and lots of data for the RA patients; Safety issues are of concern
  • Apremilast-physicians want patients to do the best that they can on the drug; there are rather respectable results with apremilast; skin response was significantly better (about 20% at PASI 75); few discontinuations due to mild AEs (laboratory parameters appeared rather normally. Lab tests probably won’t have to be done as a part of reevaluation)
CZP in PsA

Data on certolizumab was presented at ACR and it appears to work well in PsA patients who have previously been on a TNF inhibitor.

Final Thoughts
  • Obesity is a major issue in PsA patients and encouraging patients to lose weight is important to therapeutic response
  • Biosimilars (CT-P13) will be coming soon and seem to demonstrate similar efficacy, safety, and PK similar to infliximab

 

Psoriasis Update: Part 1

Emerging Therapies

Craig Leonardi, MD

Dr Leonardi began this session with an update on what’s new in the first quarter of 2013 with regards to biologic therapy. So, where have we been? Our first set of drugs was T-cell inhibitors. This was a wonderful rationale, but since then these drugs have fallen by the wayside for a number of reasons. For example, alefacept (withdrawn from market in 2012) was probably one of the least efficacious drugs approved. Efalizumab had serious infections (PML) and was taken off the market in 2009.  Our attention then drifted over to cytokines and cytokine inhibitors for the treatment of chronic inflammation. Our 2nd generation biologics are what Dr Leonardi characterizes as the TNF-alpha inhibitors.

Etanercept, in its usually approved dose, achieves a 45-50% PASI 75 response and you can get even more improvement with the double dose. Infliximab, three infusions in the first six weeks, will carry patients up to about 82% PASI 75, and then you will see a slow loss of response over time; however, still about 65% PASI 75 responders over the long term. Adalimumab achieves a 71% PASI 75 at week 16.

Third generation drugs include ustekinumab and briakinumab (withdrawn). Phase III data on Ustekinumab was positive in both the PHOENIX 1 and PHOENIX 2 studies, and demonstrates that it is a high performance drug blocking IL-12 and IL-23 showing a sustained PASI 75 response of over 80% as compared to placebo. Ustekinumab also has a nice, durable effect.

What about breakthrough early on with ustekinumab? It’s very common to see patients who have some return of disease, but just encourage patients to continue and hold on to see the positive effects.

Ustekinumab Safety Data

The 5 year safety data show that over time, adverse events on ustekinumab such infections are low and stable over time, and SAEs that lead to discontinuation seem to be low and stable as well. One caveat to keep in mind is that in any long-term safety signal monitoring study like this, patients are coming out of the trial because they either are not responding or are not tolerating the drug well.

New Development Efforts

There are several new drugs currently in development of the treatment of psoriasis. These therapies target IL-12, IL-23, and IL-17.

Ixekizumab, an IL-17 inhibitor, appears to be a very promising drug in the pipeline with almost 50 percent of patients in the studies achieving a PASI 100. As far as adverse events (AEs) are concerned, there were no serious AEs and this is extremely comforting.

The IL-17 receptor blocker, brodalumab, was studied in a variety of different dosing strategies. Brodalumab showed about an 80 percent PASI score, demonstrating a very high performance. There were a couple of serious adverse events (four), but they seemed to be unrelated to medication and no serious infections or cancers were reported.

The data on secukinumab is  difficult to explain as the studies are rather disjointed, in that, as a dermatologist, you have to look past the published data. The higher dose of secukinumab (150mg) was selected for the phase III trials because of its PASI response of approximately 81%. There were no serious adverse events with secukinumab.

Conclusions
  • We have seen an explosion of biologic drugs that are mostly targeting the IL-23 pathway
  • There are a variety of novel small molecules that are under investigation
  • JAK inhibitor may be a new topical approach
  • Short and long-term safety issues exist for therapy
  • Assess benefit/risk ratios when deciding on appropriate treatment strategies

Small Molecules For Psoriasis

Kenneth Gordon, MD

Small molecules were the mainstay for systemic psoriasis therapy for about forty years. Many patients would say that they prefer small molecules to a shot and, in fact, sometimes physicians feel more comfortable with a pill as well. In the last decade; however, all attention with regards to the treatment of psoriasis has been given to the biologics.

How will these small molecules impact our practice?

Methotrexate (MTX) is the small molecule standard and, for the most part, well tolerated. Unfortunately, some of the first studies for MTX were conducted poorly. Overall, we can expect to achieve a PASI 75 of about 40 percent with relatively aggressive MTX dosing when compared to biologics.

Apremilast

Apremilast, an inhibitor of PDE4, is currently under development for the treatment of psoriasis. In Phase II studies, apremilast (30 mg  PO BID) has achieved a PASI 75 score of about 41 percent. More than 96 percent of adverse events (AEs) were not serious. The early phase III results have not yet been released, yet a recent press release said that the studies met their clinical endpoints. Overall, apremilast seems to be well tolerated, but we don’t have the results to date.

The JAK/STAT Pathway

Tofacitinib is a novel, oral JAK inhibitor currently being investigated as a treatment for psoriasis among other indications. Although tofacitinib is a small molecule that binds to a specific area, it may have a wide range of effects; therefore, targeting various phases of the inflammatory process.

The phase II data on tofacitinib (15mg BID and 5 mg BID) demonstrate a PASI 75 response of 67 percent and 40 percent at week twelve, respectively; therefore, showing that this could be quite effective for the management of psoriasis. The issue that we have with this therapy is the overall tolerance of this medication.

When looking at some of the data that we have in rheumatoid arthritis, we see changes in baseline in hemoglobin and also lymphocyte changes. An FDA briefing document states that as the dose of tofacitinib increases, as does the risk of malignancies, this also seems to be true for lymphoma and infection. While this medication has a broader immunosuppressive effect, there may be more issues with side effects and that is something, as dermatologists, that needs to be considered.

Conclusions
  • Small molecules are again being developed for systemic psoriasis therapy
  • While they have exciting mechanisms of action, it remains to be seen if efficacy will be superior to methotrexate
  • Small molecules, since they work on multiple areas of the immune system, can have a very significant effect on the immune system

 

 

Pediatric Acne

Lawrence Eichenfield, MD

Lots of new studies have been conducted with regards to pediatric acne along with some updates to The American Acne and Rosacea Society’s Pediatric Guidelines, which have also been recently endorsed by The American Academy of Pediatrics.

For dermatologists, mid-childhood (age 1 – 7) acne is most worrisome. It can be associated with premature adrenarche, Cushings Syndrome, CAH, gonadal/adrenal tumors, and precocious puberty. The evaluation for mid-childhood acne includes testicular size (males), hirsutism, clitoromegaly, androgenetic alopecia, increased muscle mass, and deepening of the voice (males).  If the acne is persistent, severe, or virilizing, tests/examinations include a growth chart, evaluation including bone age, tanner stage, Total/Free testosterone, DHEAS, androstenedione, LH, FSH, prolactin, and 17OH-progesterone. Dermatologists should also consider a referral to an endocrinologist.

Pre-adolescent (7 ≤ 12 years) acne is common and may precede other signs of pubertal maturation. A complete work-up beyond history and physical is generally unnecessary unless there are signs of androgen excess, polycystic ovarian syndrome, or other systemic abnormalities

How should we manage preadolescent acne?

It’s important to remember that comedones are often early common on the forehead and mid-face and the truncal area is much less common. This may precede other signs of puberty. For the most part, it correlates with sebum output and sebaceous follicle numbers. P. acnes colonization is a key thing to keep in mind. **The prevalence of severity of acne of acne correlates with advanced pubertal maturation.

Acne Guidelines: Recommendations and Highlights

Acne Categorization by Age

  • Acne in neonates- 0-6 wk
  • Infantile – 0-1
  • mid-childhood 1-7
  • preadolescent 7-12
  • adolescent 12-19

 

Initial Therapy: recommendations regarding initial therapy

OTC products such as benzoyl peroxide as a single agent, topical retinoids, or combinations of topical retinoids, antibiotics, and benzoyl peroxide as individual agents or fixed-dose combinations

Topical retinoids (tretinoin, adapalene, tazarotene) may be used as monotherapy or in combination products and in regimens of care for all types and severities of acne in children and adolescents of all age

Topical Antibiotics

  • Topical antibiotics (clindamycin, erythromycin) are not recommended as monotherapy
  • If topical antibiotic treatment is to be prolonged for more than a few weeks, topical benzoyl peroxide should be added, or utilized in combination products

Oral Antibiotics

  • Oral antibiotics are appropriate for moderate to severe inflammatory acne at any age
  • Second generation tetracyclines (doxycycline, minocycline) are sometimes preferred to tetracycline because of ease of use, fewer problems with absorption, and less frequent dosing

Fixed Dose Combination Treatment

  • May be useful in regimens of care for all types and severities of acne

Hormonal Therapy

  • Second-line therapy in regimens of care in pubertal females with moderate to severe acne. Tobacco use and family history of thrombotic events should be assessed.
  • Due to concerns about growth and bone density, many experts recommend withholding OCs for acne unassociated with endocrinologic pathology until one year after onset of menstruation

Isotretinoin


  • Isotretinoin is recommended for severe, scarring, and/or refractory acne in adolescents and may be utilized in younger patients
  • Extensive counseling particularly regarding the avoidance of pregnancy, as well as careful monitoring of potential side effects and toxicities, is recommended

What about off-label treatment?

Below is a summary of some recent studies that look at off-label therapy for pediatric acne.

Tretinoin 0.04% micro-gel

  •  8-12 mild to moderate acne
  • Mean 59 lesions (9 inflammatory)
  • 12 weeks: 48% lesion count decrease
  • Tretinoin 0.04% vehicle controlled 8-11 yrs
  • Ada 0.1/BP2.5% vehicle-controlled 9-11 yrs

Retinoids

111 pt 9-11 yr olds, Retin A 0.04% micro db, vehicle controlled study, 12 wks

  • 66% prepubertal; 65 lesions (9.5 inflammatory)
  • 44% Non-inflam lesion count (vs 30%)

285 pt 9-11 yr olds, Ada .1-BP 2.5, db vc 12wks

  • 54 lesions (15 inflammatory)
  • 47% clear/almost clear (vs 15%)
  • App 50% Total lesion count decrease (vs<10%)

Oral Antibiotics

Short-term combination therapy and long-term relapse prevention in the treatment of severe acne vulgaris.

Doxycycline (DCN) and (Adapalene 0.1% – benzoyl peroxide 2.5%) = (A/BPO) or vehicle qd x 12 weeks, then A/BPO vs vehicle

  • 76% lesion count decrease

What about Isotretinoin-induced flares?

  • Appears to be a dose-related phenomenon, so start at a low dose to avoid this problem

What about prevention?

  • Systemic cyclines for anti-inflammatory effects (e.g. Mino or Doxy q day x 2 weeks)
  • Patient monitoring

 

Acne and Rosacea: Part 1

Our panel of experts in the field of Acne and Rosacea presented interesting case studies and new data that may help the practicing dermatologist improve the overall outcomes of patients in their practice.

Isotretinoin Issues

Guy Webster, MD, PhD

What are the reasons that 20% of patients do not respond to isotretinoin?

  • Inadequate dosing
  • Virilization
  • Taken on an empty stomach
  •  Young patient with bad disease

Dr Webster feels that the most common cause of isotretinoin resistance is due to patients taking the drug on an empty stomach. Data exist that demonstrate that high-fat meals enhance the absorption of the drug. A new isotretinoin, 4-oxo-isotretinoin, (brand name Absorica) demonstrated 2 times greater absorption on an empty stomach (83%) that that of the standard isotretinoin in the absence of food.

Adverse Events

Common AEs include dry skin, dry lips, high TGs, acne flare. Uncommon AEs include elevated CK, elevated AST and ALT, dry eyes, decreased night vision, depression and acne fulminans.   Acne fulminans is uncommon yet, devastating. This is most often seen early in treatment in patients with moderate to severe chest acne. To avoid this you can start with low dose, (e.g. 10mg/day or 20 mg/day) and give prednisone 20 mg/day for the first month.

Bowel disease has also been talked about in association with isotretinoin for the last thirty years. Studies found that the bowel disease was as common in the isotretinoin group as in the antibiotic group, yet both groups were higher than placebo. This could be related to the acne itself, not necessarily the medication.

Data shows that twenty-week acne therapy with isotretinoin does not affect bone. Regarding depression, there was identical risk for suicide and depression on isotretinoin as seen in that of patients on antibiotics in a very large well-powered study.

Rosacea

Hillary Baldwin, MD

We know that facial diseases cause a great deal of emotional distress. Rosacea is linked to depression and suicide and an improvement in rosacea is linked to improvement in quality of life (QOL). While teaching camouflaging/make-up techniques takes time, it does result positive effects. Many brands are available and also are accessible and affordable and in reality, minimal training is required.

Why then is it that some patients do not use makeup?

  • 53% don’t know how to use makeup
  • 29% fear it will get worse
  •  9% didn’t feel they needed it

After the use of makeup:

  •  99% made noticeable improvement
  •  99% continued to use it
  • 75% felt that it contributed to relationship with others
  • Overall improvement of QOL

Dr. Baldwin’s take home point….get familiar with a someone who knows how to do makeup and send your patients to them. It will certainly improve their QOL.

Why isotretinoin in rosacea?

It’s efficacy was first noted in 1981. There are numerous doses from 0.1-1.0 mg/kg/day. Isotretinoin improves papules, pustules, ocular disease, halts the progression of developing rhinophymas, and can lead to a reduction in erythema.

Continuous low-dose isotretinoin (10-20mg/day)

This may provide long-term control and is an alternative to antibiotics; however, appropriate monitoring necessary. Patients still have to follow iPLEDGE rules which can be difficult because they have to return monthly.

In a study with 573 patients with moderate PPR or rosacea that compared isotretinoin to doxycycline, the isotretinoin 0.3mg/kg/day dosing was found not to be inferior to doxycycline (100mg) and both were found to be superior to placebo.

Conclusions
  • In severe, refractory or recalcitrant patients, dermatologists should consider the use of isotretinoin
  • Cosmetic camouflage/makeup does work and has shown to improve patient QOL

Interesting Cases

Alan Shalita, MD

In this presentation, Dr Shalita reviewed interesting cases of acne and possible management strategies to overcome these challenging patients.

The Patient with Sandpaper Comedones

This is a rare condition that is often times difficult to treat. Dermatologists can try compounded tretinoin solution (0.05%), which can be very, very irritating but effective and possibly TCA peels, with the right concentration. Laser abrasion may be effective if you have access to a CO2 laser. Another technique that can provide some relief is what Dr Shalita refers to as “vacuum suction.”

What about chin acne?

Chin acne is typically found in young adult women and may involve the mandible and adjacent neck. Chin acne may or may not be hormonal, but frequently improves with the use of a combination of  both oral contraception and spironolactone. Oral antibiotics can also be helpful. Topical therapy is often times too irritating for patients.

Patients with Nodulopustular Acne

Many dermatologists withhold isotretinoin treatment for too long. If this is the case, you may occasionally need I&D. It is recommended to start on low isotretinoin (target: total dose 120-150 mg/kg) and you may need to culture if the patient is not responding.

Primary Irritant Reaction

This is more common in fair skin, but can occur in all skin types. In many cases, it was a common reaction to topical retinoids; however, it can also result from peels and cryotherapy. Dr Shalita finds that topical tretinoin is effective.

Summary
  • Take time with your patients
  • Topical retinoids should be used in all but he most severe forms of acne
  • Benzoyl peroxide reduces or eliminates less sensitive organisms
  • Antibiotics: Minocycline>Doxycycline>Tetracycline- (forget erythromycin)
  • Isotretinoin: Start low; consider adding steroids to avoid acne fulminans
  • Don’t be afraid to use hormonal therapy

Infectious Disease Update: Year in Review

Andrew Blauvelt, MD

Dr Blauvelt presented an update on important information and data on infectious diseases that were published in some of the top tier medical journals in 2012 and their clinical implications for the practicing dermatologist.

 Clinical Pearls
  • Look for Staph. Aureus infection in and around implantable electronic devices-these were associated with hematomas and wound healing; recommended treatment was complete removal of the device and antibiotic therapy
  • Be aware of possible bacterial contamination in antiseptic products in the office; of note, antiseptic products are NOT required to be manufactured under sterile conditions (currently under review by the FDA)
  • Erythema migrans in persons with a history of Lyme Disease most likely represents reinfection and not recurrent disease
  • Tattoos may be infected with mycobacteria contaminating the tattoo ink. Tattoo ink does not have to be manufactured in sterile conditions. M. Chelonae was found recently in a batch of tattoo ink. Diagnose, treat, and report accordingly
  • Travel history is important for a sick patient with cutaneous abscesses.  Meloidiosis, a disease caused by environmental (in soil) gram-negative bacillus Burkholderia pseudomallei, presents with multiple cutaneous abscesses and pneumonia. It has a 40% mortality rate.
What about viruses?
  • Adults born from 1945-1965 should receive one time testing for the hepatitis C virus without prior assessment of HCV risk (recommendation from the CDC)
  • All persons identified with HCV infection should receive brief alcohol screening/intervention as indicated followed by an appropriate referral to a specialist
  • Clinical data and ex vivo experiments that show pre-exposure prophylaxis with anti-HIV drugs can block subsequent infection; however, controversy exists over ethics, practicality, and cost
  • Genital herpes simplex virus 2 (HSV-2) enhances sexual transmission of HIV
  • Antiviral medication for the treatment of HSV-2 using short courses of high-dose acyclovir and valacyclovir (1 gram TID) may decrease outbreaks, but does not prevent  subclinical HSV-2 genital shedding of the virus.  The therapy does decrease shedding by about 50% but the rate of breakthrough shedding was 16-20 episodes/year. Novel therapies need to be developed to block shedding
More Clinical Pearls
  • Live vaccines may be safer in the setting of biologic therapy than previously believed.  In a study of MCR patients receiving biologics, 633 patients were inadvertently vaccinated with the herpes zoster vaccine. None developed varicella or zoster.
  • In addition to previously identified in EVER1 and EVER2 genes, epidemodysplasia verruciformia may be caused by a genetic defect in RHOH which leads to T cell defects
  • Injectable corticosteroid products may be contaminated during the compounding or manufacturing process
  • Natural disasters can lead to unusual medical conditions.  Mucormycosis, caused by infection with ubiquitous molds in soil and decaying wood, resulted in 13 cases of mucormycosis resulting in 5 deaths in storm affected areas. The median number of wounds through which the mold penetrated was 5.
  • Bilateral leg lymphedema, which can lead to elephantiasis verrucosa nostra, is associated with obesity (and not filariasis in non-endemic areas).  The average BME was 51.4.
  • Topical 0.5% Ivermectin lotion is a promising new therapy for head lice. In two large studies, a single application of 0.5% ivermectin applied to dry hair, left for 10 minutes, and then washed off resulted in nearly 75% of patients being louse free at day 15.  Nit combing in not necessary because ivermectin if both pediculocidal and ovacidal.
Aditya Gupta, MD, PhD

Dr Gupta, one of the leading authorities in the world on fungal infections, provided the audience with an update onychomycosis and how dermatologists can improve upon the management of this condition.  Dermatologists should be aware of the prevalence of onychomycosis and this may help practitioners understand why patients may fail certain therapies. There are various therapies available for onychomycosis including oral therapy, topical therapy, and devices.

Oral Therapy

Terbinafine is probably the gold standard for the management of onychomycosis. Dr Gupta and his colleagues studied various terbinafine dose regimens and found that 2 pulses 250mg/day 4 weeks on/4 wks off/4 wks on appeared to have the best outcomes; however, there was not a significant difference between continuous and pulsed regimens.  It is important that dermatologists understand the existing data on the various antifungal medications currently available in order to apply this information into clinical practice.

Topical Therapies

The nail plate is the greatest barrier when treating fungal infections. Currently, ciclopirox is the only topical therapy approved in the United States. However, there are emerging therapies currently under investigation.

Device Therapy

There are lots of questions about laser therapy. Podiatrists seem to use laser therapy quite often; yet, dermatologists continue to raise questions about their effects and how they actually work. Laser therapy poses the same challenges as those of topical therapies. To date, there is only one published trial (n=13) and the study demonstrates an efficacy rate of 51%. More studies are needed to determine if laser treatment is effective.

In conclusion, dermatologists need to recognize the importance of the choice of agent for onychomycosis and identify other important management strategies that may help to improve the outcomes of their patients.

 

 

 

Emerging Technologies in Dermatology

Rox Anderson, MD

In this presentation, Dr Anderson reviewed some of the emerging technologies in the field of dermatology. Topics discussed included:

  • Microscopy
  • Epidermal blister transfer blasting
  • Restoring elastic recoil
  • “Targeting” sebaceous glands

“Optical tools are used quite often in diagnostics in the field of dermatology and the ability to get true microscopic cross-sectional imaging is coming our way.” For example, Optical Coherence Tomography (OCT), an exciting clinical advancement, will soon be hands of dermatologists providing practitioners with the ability to conduct true microscopic tomography of the skin.

How can one practically conduct epidermal blister grafting?  Dr Anderson’s group has been researching a process for replacing radiation-damaged skin with non-damaged epidermis of the same patient. This process has shown to be both cost-effective and timely, in that, significant improvement was seen in six months. This process could potentially be applied to conditions such as vitiligo, radiation injury, field cancerization, wounds, ulcers and other dermatologic disorders.

“One of the problems with aging is that we lose our elastic recoil.” This year, there has been some interesting information on the role of fractional lasers and the loss of elastic dysfunction. Can you artificially restore the elastic of the skin? These processes are in the pipeline and may one day be available.

Whatever benefit we get from sebaceous glands is outweighed by acne. What would happen if we move sebaceous glands? In the 1990s, research thought that most likely, there would be no acne and the process would be analogous to laser hair removal. Could lasers used at a certain wavelength selectively kill sebaceous glands? The answer is yes, if you have access to a laser at 1720 nm.  The histological results are good and perhaps in the future scientists will develop a laser that will be capable of treating acne.

 

 

 

Debunking the Myths of Sunscreen

Curtis Cole, PhD

Dr Cole, VP of R&D at Johnson and Johnson Consumer Products reviewed some of the facts and myths about the use of sunscreen.

Currently, there is lots of confusion about the use of sunscreen. Many believe that sunscreen use is doing more harm than good due to hormone disruption, “nano” materials, and organic versus inorganic filter-based products.

We know that ultraviolet radiation from the sun is the major cause of skin cancer and sunscreens diminish the amount of UV rays that are exposed to the skin.

Common Questions

Are physical blockers really different from chemical filters? It’s important to know that ZnO and TiO2 have a semiconductor energy band gap and really act as absorbers and work like chemical filters.

What about sunscreen re-application? Do they need to be applied every two hours? Sunscreens will keep working indefinitely as long as they are photostable; however, re-application does help increase the protection and it is mandatory labeling by the FDA.

“Broad spectrum” is determined by critical wavelength. What do critical wavelengths really mean? Dermatologists should remember that critical wavelength does not necessarily imply protection. The new FDA labeling has changed what critical wavelength actually means.

Do SPFs greater than 50 provide more protection? Dr Cole reminds us that protection is directly proportional to the SPF number. Therefore, a higher SPF number is better protection for many conditions. Additionally, he presented data demonstrating that sunscreen application of a higher SPF  (SPF 85) provided superior protection when applied sparingly compared to lower SPF (SPF 30) sunscreens.

Summary
  • Sun protection has improved immensely over the last ten years
  • Sunscreens are only part of a multi-layer defense
  • Sunscreen use will do far more good than harm

 

 

 

 

 

What’s New in Bullous Disease?

John Zone, MD

Dr Zone, a leading expert in immunodermatology, presented some of the latest data on the management of bullous diseases.

Therapies discussed included:

  • Rituxumab (off label) -Pemphigus/mucus membrane pemphigoid
  • IVIg (FDA approved)-Pemphigus/Pemphigoid
  • IVIg (FDA approved)-Controversial for Toxic epidermal necrolysis (TEN)/Stevens-Johnson syndrome (SJS)
  • IVIg (off label)-Scleromyxedema
  • IgE and Omalizumab (off label)

Rituximab has demonstrated positive efficacy for the treatment of both pemphigus and mucus membrane pemphigoid.  Intravenous Immune Globulin (IVIg) is FDA now approved for a variety of dermatologic disorders, and because of the thousands of donors, it is rather accessible.   The efficacy of high dose IVIg in the treatment of TEN has been studied and it has demonstrated positive results in adults; however, it is important to keep in mind that IVIg is not benign and adverse effects can occur.

What about scleromyxedema? Scleromyxedema is a rare disease with mucin deposition in the skin and other organs with monoclonal IgG protein. In a case series report, the data on IVIg therapy for scleromyxedema was positive. Finally, Dr Zone feels that in the next ten years IgE will really “catch on.”  Omalizumab can treat diseases such as urticaria, pemphigoid, atopic dermatitis and many more disorders.

 

 

 

 

Pediatric Dermatology

Our expert panel of pediatric dermatologists reviewed various topics in the field of pediatric dermatology including, hemangiomas, nail diseases, atopic dermatitis, inflammatory disorders, and skin lesions.

Drs Friedlander and Frieden began the pediatric dermatology session with a discussion on infantile hemangiomas (IH). Dermatologists need to continue to understand the incidence and pathogenesis of IH and when to recognize when intervention is required. A large prospective study showed that overall 4.5% of infants were affected by IH. Where do infantile hemangiomas come from? There are three theories: 1. Placenta embolization; 2. Somatic mutation in gene mediating endothelial cells (VEGF); 3. A hypoxic location elicits production of HIF.

How do we treat IH?

Over the last four years, Beta Blockers have emerged as a novel therapy for the treatment of IH. Guidelines were recently published for the use of propranolol in patients with IH. (Drolet et al. Pediatrics 2012 December 24. Epub ahead of print) A recent systematic review compared the improvement of IH with propranolol versus steroids and the results were 98 percent and 71 percent, respectively. The adverse events were also higher in the steroid group versus the propranolol group. All patient vital signs should be monitored when given propranolol; the most frequent side effect is hypoglycemia.

What if propranolol is not an option? The topical beta blocker, Timolol (which has been use for years in glaucoma patients with great safety), has encouraging results and appears to be well tolerated. This has been effective in facial lesions particularly around the eye.  For lesions near the eye in neonates 1 drop BID is the generally accepted dose.

Other therapy for IH includes corticosteroids, systemic therapy, pulsed dye laser, cryotherapy and Imiquimod.  An important concept with the overall management of hemangiomas is that management is not a “one size fits all” approach and therapy needs to be individualized.

Hand-Foot-Mouth and Beyond…

Over the last few years, atypical cases of HFMD have been reported to the CDC. Many of these cases looked like eczema herpeticum, but oral erosions and palmar lesions looked like HFMD. Coxsackie A-6 infection seems to be a virus that is now appearing in clinical practice. Fortunately, multiple PCR panels are commercially available and can aid dermatologists in the detection of these worrisome viruses.

What about onychomycosis?

Dermatologists need to remember that fungal nail infections DO affect children and the incidence may be increasing due to occlusive foot lifestyle and genetics. **Utilizing a curette is a good way to obtain a nail specimen in a child without provoking fear or fuss. Terbinafine 5mg/kg/d is an effective systemic therapy used to treat onychomycosis as well as fluconazole. Data has also shown that that children, with Onychomycosis not involving the matrix, can be effectively treated with topical ciclopirox lacquer.

Atopic Dermatitis

Dr Eichenfield addressed atopic dermatitis in the pediatric population. Key takeaway messages included:

What is the association between filaggrin and AD? Not all patients have filaggrin mutations and fillagrin mutations vary in AD patients from country to country. However, filaggrin expression decreases with inflammation even in AD patients without filaggrin mutations. When treating these patients, address the barrier, i.e., hydration.   How do we best treat pediatric AD patients? Anti-inflammatory treatment is effective and proper education can help to improve therapeutic outcomes.  It is also important to remember that microbes are not just bacteria, inflammation decreases diversity and increases staph infection; bleach baths and other products can be used as reasonable adjuvant therapy.  Mental health conditions, such as ADHD, are associated comorbidities among AD patients. Family attention and appropriate screening may be necessary.  In conclusion, don’t forget about allergy in AD patients; selective testing for foods may be beneficial.

Inflammatory Disorders

Dr Cordoro discussed inflammatory disorders in pediatric patients and what to do when creams aren’t enough to effectively manage these conditions. Because of the lack of data and treatment guidelines currently available for the pediatric population, managing these disorders with systemic and biologic therapies can be challenging for dermatologists. Different factors can affect and determine the appropriate therapeutic choice.

Practical Pearls for the Use of Systemic Therapy in the Pediatric Population
  • Let explosive –onset psoriasis evolve a bit before committing to systemic therapy
  • When you need speed, choose cyclosporine
  • Oral retinoids are often the best initial choice for sever guttate and pustular psoriasis in children
  • Is there a place for biologic therapy in children with psoriasis? The answer is yes.
  • Remember to assess which is worse: the disease or the treatment. Do not withhold treatment because “nothing is approved for use in children”