A look at new and exciting advances in the field of dermatology.

Another year has brought several new and exciting advances to the field of dermatology. This review will highlight new and pertinent knowledge of the pathophysiology and treatment of skin diseases as well as regulatory developments that will affect your practice. Categories that will be discussed include infectious disease, acne, psoriasis, photoprotection, pediatric dermatology, cutaneous neoplasms, contact dermatitis, biologics and cosmetics. Topics explored include new medications and products relevant to the field of dermatology, as well as updates to medication labels, and pertinent news in the field.

Infectious Disease

Ulesfia

Benzyl alcohol lotion 5% (Ulesfia) has been approved by the FDA as the first prescription medication that kills head lice by asphyxiation without neurotoxic side effects. Pediculosis capitis is spread by head-to-head contact and by fomite transmission.1 Resistance to traditionally used permethrin and malathion is well documented.2 Thus, the availability of a new head lice treatment is welcome.

In two studies of more than 600 people with active head lice infestation, Ulesfia was compared with placebo. Subjects received two 10-minute treatments of either Ulesfia or placebo where treatments were separated by a week. Greater than 75% of subjects who had applied Ulesfia were clear 14 days after the second treatment. Only 26% of patients who used placebo were free of lice.3 Ulesfia is approved for children 6 months and older. Intravenous administration of benzyl alcohol–containing products have been associated with an entity known as neonatal gasping syndrome, which has been found in preterm, low birth weight infants and is defined by severe metabolic acidosis, gasping respirations, progressive hypotension, seizures, central nervous system depression and death.4 Thus, it is feasible that Ulesfia could induce neonatal gasping syndrome in this population and should only be used in patients 6 months of age and older, as per FDA requirements. Side effects include eye irritation and contact dermatitis. In the two clinical trials and one open-label study that have been performed with Ulesfia, side effects were noted in 478 patients. Only 2% of patients had application site irritation, 2% reported application site anesthesia, and 1% noted pain at the application site. Other side effects in those who did not experience these prior to Ulesfia application included pruritus 12%, erythema 10%, pyoderma 7% and ocular irritation 6%. Ulesfia is pregnancy category B.4

Possible Off-Label Use for Zoster Vaccine

The herpes zoster vaccine is currently licensed for immunocompetent individuals 60 years and older. At a recent conference on pediatric infectious diseases sponsored by the Children’s Hospital in Denver, Dr. Myron J. Levin suggested that the herpes zoster vaccine should be given to children who are or who are about to be immunocompromised, such as those awaiting a transplant.5 Patients who receive the zoster vaccine should have already had chicken pox. This will avoid giving the vaccine to a naïve person, thus avoiding serious side effects from the vaccination. Current recommendations are that the vaccine should be avoided in the severely immunocompromised.

Vibativ

Theravance, Inc., and Astellas Pharma, Inc., have received FDA approval to market a new antibiotic for hard-to-treat skin infections, such as methicillin-resistant Staphylococcus aureus (MRSA), in the United States. The FDA approved telavancin in September as a once-daily infusion and it will be called Vibativ. Telavancin is a rapidly bactericidal lipoglycopeptide and has multiple mechanisms of action. One mechanism of action Telavancin exhibits is concentration-dependent inhibition of bacterial cell wall synthesis and disruption of the functional integrity of the cell membrane.6 Side effects reported include taste disturbance, nausea and vomiting.

Telavancin includes a “black-box” warning for pregnant women, as adverse developmental outcomes have occurred in three animal species (rats, rabbits, and minipigs) at clinically relevant doses; no human pregnancy data is available. Telavancin is labeled pregnancy category C. Serum pregnancy test should be performed before administration.7

Telavancin is an important addition to the armamentarium against serious infections caused by resistant Gram-positive cocci, especially infections produced by MRSA.

Bioguard Barrier Dressing

The Bioguard Barrier Dressing offers an effective and affordable novel option to aid in the battle against Methicillin-resistant Staphylococcus aureus (MRSA). The FDA has cleared Bioguard as the first barrier dressing. Bioguard is a gauze-based dressing that has been shown to kill 99.999% of MRSA.8 The dressing has a non-leaching bond between the dressing substrate and the active agent. Bioguard contains a nimbus cationic biocide, which is permanently bonded to the gauze. This biocide helps to keep bioguard from depleting in the presence of wound fluid and bacteria, while killing microbes that are drawn into the absorbent dressing.

Acne/Rosacea

Epiduo

A fixed combination of adapalene 0.1% and benzoyl peroxide 2.5% (Epiduo) was approved by the FDA in December 2008 for acne.9 This combination of acne treatments targets different aspects of the pathogenesis of acne through different modes of action. This dual action has the potential for better results than monotherapy. Adapalene is anticomedogenic, comedolytic and anti-inflammatory. Benzoyl peroxide has antimicrobial actions. In a multicenter, randomized double-blind controlled study involving 517 patients, fixed-dose combination of adaplaene and benzoyl peroxide was shown to be more effective than adapalene or BPO alone.10,11

Triaz

The Triaz line adds to its treatment options against acne vulgaris with benzoyl peroxide 6% foaming cloths (Triaz Foaming Cloths).12 The packaging of a single cloth for one-time use allows for ease of use and convenience.

Acanya

Clindamycin phosphate 1.2% and benzoyl peroxide 2.5% (Acanya Gel) was approved in October 2008 for acne vulgaris.13 (See Figure 1.) In two double-blinded multicenter randomized studies where 2,813 patients with moderate or severe acne were treated with clindamycin-BP 2.5% vs. either active ingredient vs. vehicle gel, the clindamycin-BP 2.5% group showed significant reduction in acneiform lesions compared to the other groups.14

Roche and Accutane

In June 2009, Roche announced it would no longer be selling isotretinoin (Accutane) due to losses as a result of generic sales. Isotretinoin will now be available only in generic form.15 Generic isotretinoin is available through the following companies: Mylan Pharmaceuticals, Inc., (Amnesteem); Ranbaxy Laboratories, Inc., (Sotret); and Barr Laboratories, a division of Teva (Claravis).16 Isotretinoin is sold only under the IPLEDGE program, a program approved by the FDA due to the teratogenic effects of isotretinoin. Unfortunately, at this point, no patient assistance program is offered for generic isotretinoin through Mylan, Ranbaxy, or Barr Laboratories.

Solodyn

Minocycline HCL (Solodyn) was FDA approved in February 2009 in 45 mg, 90 mg, and 115 mg extended release tablets. In July 2009, two new strengths of Solodyn, 65 mg and 115mg, were approved by the FDA,17,18 making it now available in five strengths. Solodyn is approved for moderate to severe acne vulgaris in patients 12 years and older. It is the only oral minocycline that is branded approved for once-daily dosage. Although no studies have been published with this 90 mg tablet of Solodyn, a study in 2006 showed that an extended-release minocycline formulation that delivers consistent levels of drug at a 1 mg/kg dose reduces dose-dependent acute vestibular adverse events while reducing inflammatory lesions and improving the overall appearance of patients with acne vulgaris.19 This potential for a single dosing regimen may also lead to improved compliance.

Psoriasis

Simponi for Psoriatic Arthritis

The anti-TNF-α monoclonal antibody, golimumab (Simponi), was approved for treatment of active psoriatic arthritis, as well as moderately to severely active rheumatoid arthritis, and active ankylosing spondylitis.20 Simponi has been shown to improve active psoriatic arthritis and associated nail and skin findings of psoriasis.21 Simponi is a once monthly subcutaneous injection for adults with the above diseases.

Scytera

Coal tar foam 2% (Scytera) is a new treatment for psoriasis. Scytera, a 10% coal tar topical solution, is available in a 3.3 oz can. It is the first coal tar formula in an aerosol foam vehicle.22 Coal tar has been used for years in the treatment of psoriasis. Coal tar treatment of psoriasis results in a reduction in the overproduction of skin cells, a reduction of itch and a promotion of healthy skin. Coal tar products of the past have had limitations due to their strong odor, potential to stain and unappealing texture.23 Scytera brings the efficiency of coal tar, while improving upon its unpleasant aspects.

Stelara

The FDA has approved ustekinumab (Stelara). (See Figure 2.) This new drug was approved September 2009 by the FDA for the treatment of moderate to severe psoriasis in adults (18 years or older) who are candidates for phototherapy or systemic therapy.24

A human monoclonal antibody, Stelara blocks interleukins 12 and 23 by binding to the p40 protein subunit. Stelara is administered by injecting it under the skin once every 12 weeks after two initial doses. The recommended dose for patients under 220 lbs is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. For those > 220 lbs, the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. Two large phase III trials in patients with moderate to severe plaque psoriasis showed that patients who received 45 or 90 mg of subcutaneous Stelara achieved a 75% improvement on the Psoriasis Area and Severity Index (PASI 75) score at 12 weeks in comparison to placebo. Physician’s global assessment of clinical response at week 12 also favored Stelara over placebo. Phase II trials showed patients with active plaque psoriasis and psoriatic arthritis had improved symptom control when compared to placebo at 12 weeks based on the proportion of patients achieving a 20% improvement in American College of Rheumatology response criteria or PASI 75.25

Stelara may increase the risk of infections and may reactivate latent infections. Patients must be evaluated for tuberculosis prior to initiation of treatment. There may be an increased risk of malignancy and reversible posterior leukoencephalopathy syndrome in ustekinumab-treated patients. Patients should not receive live vaccines while on ustekinumab.

Vectical

The FDA has approved calcitriol ointment (Vectical), a vitamin D analog, for topical treatment of mild-to-moderate plaque psoriasis in adults 18 years of age and older. Calcitriol, is the naturally occurring active form of vitamin D3. It has been used in other countries for many years for the treatment of psoriasis and now is approved in the United States under the trade name Vectical. Two randomized, double-blind clinical trials, showed that twice-daily application of calcitriol ointment for 8 weeks was more effective than vehicle in psoriasis. Patients using Vectical resulted in clear or minimal residual psoriasis in approximately 34% of patients, compared with 12% to 22.5% of patients treated with vehicle ointment.26

Photoprotection

EltaMD now Paraben-Free

Parabens, which have been used as preservatives in medications and over-the-counter preparations for many years, are a well-known cause of contact dermatitis. EltaMD has now created sunscreens that are paraben-free, thus offering a new UV protection option for those with sensitive skin.27

Best-Rated Sunscreens 2009

Consumer Reports studied the protection of sunscreens against ultraviolet A and B radiation as well as how long sunscreens remained on volunteers who were immersed in water for 40 minutes or longer. Consumer Reports noted that most products tested protected well against UV. However, Banana Boat Kids Tear Free SPF 50 was only fair in UVA protection, was difficult to rub in and left white debris on the skin. All products tested for UVB protection met their SPF claim with the exception of Neutrogena’s Ultra Sheer Dry Touch SPF 70;28 although it was shown to come within 10% of its claim, this was the most expensive sunscreen tested. No sunscreens lost more than 10% of UVB protection after water immersion. Aveeno’s Continuous Protection Spray SPF 45 did not lose any in the study. Consumer Reports’ best performers were lotions and sprays, but sprays were noted to be less reliable due to the possibility of windy days.

Cutaneous Malignancy

FDA Accepts New Drug Application for New Imiquimod Product

The FDA has accepted a new drug application for imiquimod 3.75%.29 Currently the 5% imiquimod formulation (Aldara) is indicated only for the treatment of nonhyperkeratotic, nonhypertrophic actinic keratoses on a very limited area of the skin, less than 25 cm,2 for 16 weeks of treatment. The goal of the clinical studies conducted with the new 3.75% imiquimod formulation is to evaluate a new treatment regimen for actinic keratoses patients with extensive disease (5 to 20 AK lesions over the full face or scalp) over a shorter time period.30,31

Peplin Initiates Final Phase III Clinical Trial for PEP005 Gel in AK

Inogel mebutate, also known as PEP005, is a diterpene ester that is extracted and purified from the plant Euphorbia peplus. Inogel is being evaluated as a topical therapy for actinic keratosis.32 The mechanism of action of this inogel is localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, scaling and crusting.

In a recent study, patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. The partial clearance rate for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel. The complete clearance rate was also significantly higher for patients in the ingenol mebutate gel.33,34 Inogel is being developed as a new treatment for actinic keratoses. This completes enrollment in the last of four pivotal trials planned for the submission of the new drug application for AK.

Indoor Tanning

AAD Commends Reclassification of Tanning Beds as Carcinogenic — The International Agency for Research on Cancer (IARC) re-categorized indoor tanning devices as carcinogenic to humans. The AAD commended the IARC on this change. This classification places indoor tanning in the highest cancer risk category afforded by the IARC, a division of the World Health Organization.35,36

Tanning Laws — Legislation that would newly restrict the indoor tanning industry or strengthen existing laws were introduced in 21 states, adding to the 29 states that already have laws on the books regulating tanning by minors, according to the National Conference of State Legislatures.37 In March, Arkansas and Mississippi signed a new law that restricts access for minors under the age of 14 years old to go to tanning beds. Texas legislation requires that anyone under the age of 18 present a doctor’s note to use a tanning bed, as well as have a written consent from and be accompanied by a parent. Ohio presented a proposal to prevent people under the age of 18 from using tanning facilities unless they present a prescription for UV radiation treatments from a licensed physician. This spring, Arkansas and Mississippi each passed legislation requiring that minors have signed parental consent for use of tanning facilities. Wisconsin prohibits any child under age 16 from using tanning facilities. Illinois, New Jersey and New York prohibit children under 14 from tanning.38

UK Survey Supports Need to Protect Children — A recent survey taken in the UK showed that young patients were more likely to be sunburned, reaffirming the importance of sunprotective education to this population.39

Pediatric Dermatology

Propanolol for Infantile Hemangiomas

Corticosteroids have been the main treatment for severe infantile hemangiomas, while interferon and vincristine have been used as second- and third-line treatments. These medications are all limited due to their side effects and limited efficacy.

A case series in France of 32 patients showed that propranolol is effective in treating severe infantile hemangiomas.40 The hemangiomas in the case series responded dramatically to propranolol with overnight softening and color change after one dose. In the published French case, a positive effect on the growth of hemangiomas was noticed among infants treated with beta-blockers for hypertension. At Johns Hopkins Medical Center, the director of pediatric dermatology, Dr. Cohen, had good results as well. Propranolol has shown consistent, quick efficacious benefits in infantile hemangiomas.41,42 Larger studies are needed to confirm these results. If confirmed, propranolol could become first-line treatment for infantile hemangiomas.

Cosmetic Dermatology

Latisse

Bimatoprost 0.03% solution (Latisse), a prostanoid F2alpha receptor agonist, was FDA approved for daily use on the upper eyelid to increase the length of eyelashes. The effect of enhanced eyelash growth was noted by glaucoma patients using the drug (known as Lumigan).43 Latisse adds an option for enhanced eyelash growth in the general public. A single nighttime application to the top eyelids allows for ease of use.

Dysport

AbobotulinumtoxinA (Dysport) is an acetylocholine release inhibitor and a neuromuscular blocking agent indicated for adults with cervical dystonia and temporary improvement in glabellar lines. This is the second botulinum toxin drug approved by the FDA for wrinkle treatment. Dysport is made from Clostridium botulinim toxin type A.44,45

OnabotulinumtoxinA (Botox/Botox Cosmetic) and AbobotulinumtoxinA (Dysport) and RimabotulinumtoxinA (Myobloc) are the three current FDA-approved botulinum toxins. Botox Cosmetic is FDA-approved for temporary improvement in the appearance of moderate to severe glabellar lines, while Dysport is indicated for cervical dystonia and temporary improvement in the appearance to moderate to severe glabellar lines. Both drugs contain the same main ingredient, botulinumtoxinA. Dysport is administerd via injection as is Botox. Initial reports suggest that Dysport may act more quickly than Botox, but that Botox may last longer.46,47

Boxed Warnings Required for Botulinum Toxin Products

The FDA announced in April 2009 the need for safety label changes, including a boxed warning, for all botulinum toxin products. This action was taken after reports that the effects of the botulinum toxin could spread from the area of injection; these findings were reported mostly in cerebral palsy patients injected with botulinum toxin for muscle spasms.48 The spread of the toxin reportedly caused botulism-like symptoms including loss of strength, muscle weakness, hoarseness, urinary incontinence, dyspnea, swallowing trouble, diploplia, blurred vision and drooping eyelids.

Botox, Myobloc and Dysport are approved by the FDA for the treatment cervical dystonia. Botox Cosmetic and Dysport are approved by the FDA for dermatologic use in the temporary improvement in the appearance of glabellar lines. Botox is also approved for the treatment primary axillary hyperhidrosis, strabismus, and blepharospasm.

Impruv Line

In March, Stiefel released a new line of dry skin products called Impruv at Walgreens. Impruv Natural Repair products contain six botanicals — coconut oil, palm oil, olive oil, wheat germ, soy and shea butter — to help improve dry skin and restore the body’s natural moisture.49

Radiesse

BioForm Medical introduced two more economical forms of Radiesse. Radiesse, a wrinkle filler that is implanted subdermally, is FDA-approved for correction of moderate to severe facial wrinkles and folds.50 The 1.3 cc Radiesse dermal filler syringe has been replaced by the 1.5cc Radiesse Volume Advantage syringe, which supplies 15% more of the filler at no additional cost. Another size, the 0.8 cc Radiesse Moderate Fill syringe, has been listed for $199 to physicians. This 0.8 cc Radiesse enables physicians to use Radiesse less expensively without needing other products with less volume.

Kerafoam 42

In May 2009, Onset therapeutics launched a 42% urea emollient foam (Kerafoam 42), which is a higher concentration urea foam indicated for smoothing hyperkeratotic skin conditions. This new Kerafoam product is alcohol-free, fragrance-free and odor-free.51 Kerafoam 42 provides an alternative for patients who require a higher concentration of urea; it not only helps exfoliate hyperkeratosis, but also restores the natural skin barrier function.

Refissa

A new 0.05% tretinoin cream (Refissa) entered the dermatology world. It is fragrance-free and contains an emollient moisturizing base. Refissa is indicated for aiding fine wrinkles, dyspigmentation, and skin roughness. Refissa is available in a 40g tube.52,53

Sculptra Aesthetic

In July 2009, the FDA approved Poly-L-Lactic Acid (Sculptra) as aesthetic treatment to correct nasolabial fold rhytids and other facial rhytids. Sculptra Aesthetic is an implant of poly-L-lactic acid microparticles. It has been approved for lipoatrophy in HIV patients since 2004.54,55

Evolence

In a November 3 announcement, Ortho announced its “intention to discontinue the manufacture and marketing of Evolence products.” The announcement included reassurance about the safety and efficacy of the product for approved indications, and made clear the company’s continued support “for medical inquiries and adverse event reporting, in accordance with regulatory requirements.”

Biologics

Updated FDA Warnings for TNF Blockers

Increased Risk of Cancer — In August 2009, the FDA updated warnings on TNF blockers infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi) to include increased risk of lymphomas in children and adolescents treated with TNF blockers.56 The update also included reports of leukemia in adults and children. The FDA concludes from the malignancy reports that children and adolescents treated with a TNF blocker for an average of 30 months have an increased risk of malignancy.57 About half of the cancer cases were lymphomas. The prescribing information already warned about the increased rate of lymphomas in the adult population.

New-onset Psoriasis — An update to the adverse events section included reports of cases of new-onset psoriasis that occurred in patients who had not reported psoriasis before. In about half of the cases, patients’ new-onset psoriasis was the pustular or palmoplantar form.58 In most, once treatment was stopped, the psoriasis improved. After reports of progressive multifocal leukoencephalopathy (PML) in three patients with psoriasis treated with Raptiva in the absence of any other concurrent immunosuppressive agents arose, the manufacturer voluntarily withdrew this drug from the market.58

Risk of Fungal Infections — The FDA recommended that the manufacturers of Humira, Cimzia, Enbrel and Remicade update the existing Warnings and Precaution sections of the drugs’ prescribing information and Medication Guides on the risk of developing opportunistic fungal infections.59 Since the initial approval of these four TNF blockers, prescribing information included information about the risk of serious infections, but, based on FDA-reviewed reports, healthcare professionals were not consistently recognizing invasive fungal infections, leading to delays in treatment and death. Patients on TNF blocker drugs with fever, cough, shortness of breath or fatigue should be told to contact their physician immediately.

Contact Dermatitis

Contact Allergan of the Year — The American Contact Dermatitis Society named mixed dialkyl thioureas Contact Allergen Of The Year.60 Mixed dialkyl thioureas are a mixture of two thiourea chemicals used for rubber acceleration and in the manufacturing of neoprene.61

Current Events

Healthcare Reform

President Barack Obama has clearly explained that he wants a healthcare reform bill by the end of 2009.62 There will likely be many changes to all of health care. How it will affect the practice of dermatology is yet to be shown.

H1N1 Swine Flu

No cutaneous manifestations of H1N1 swine flu have been reported to date. The vaccine made available to high-risk groups in October was still in relatively short supply at press time. The government plans to track possible side effects when mass flu vaccinations begin. In the ongoing clinical studies, the FDA reports the vaccines have been well tolerated. Potential side effects of the H1N1 vaccines are expected to be similar to those of seasonal flu vaccines including soreness at the injection site, mild fever, body aches and fatigue for a few days after the inoculation. For the nasal spray vaccine, the most common side effects include runny nose, nasal congestion, sore throats and fever in children.63

GlaxoSmithKline Completes Acquisition of Stiefel

GlaxoSmithKline has now acquired Stiefel. This merger is expected to help GSK diversify and grow. Currently, Stiefel makes the following medications for dermatological use: Stiprox, Olux, Olux-E, Evoclin, Revaléskin, Brevoxyl, Oilatum, Luxiq, Duac, Versafoam and Mimyx.64

Vitamin D Controversy

UVB radiation is necessary for the synthesis of vitamin D in the skin. As dermatologists, we advise avoidance from the sun, sun protective clothing and sunscreens to prevent future cutaneous carcinogenesis. Yet over the past several years, the new evidence has shown that vitamin D has important effects on health and disease. This has raised the concern that by protecting ourselves from the sun’s UVB and depleting vitamin D, we may be at risk for other diseases.65,66

Vitamin D deficiency is well known to cause rickets and osteoporosis. Evidence has also suggested that vitamin D may have a role in preventing malignancies, particularly colorectal cancer. In a recent study published in the Journal of Clinical Oncology, the medical records of 872 patients with melanoma were reviewed. Patients with higher levels of vitamin D had thinner melanomas and a lower rate of relapse suggesting a protective nature of vitamin D.67

Thus, there is significant controversy between medical specialties with respect to vitamin D and how to obtain it. The AAD currently recommends supplementation: 400 or 1000 IU of vitamin D daily with or without calcium or in a multivitamin;10,000 IU weekly or every 10 days; or 50,000 IU monthly with maintenance of sun protection. Foods high in vitamin D, such as fortified cereals and fatty fish are also recommended as part of a balanced diet. Vitamin D levels should be monitored for appropriate increase with supplementation. Ongoing investigation will continue with respect to vitamin D and its effects on health.

Summary

This ends this year’s Year in Review. Hopefully, this review has highlighted for you important updates in dermatology and will aid you in your practice. Here’s to 2010!

Dr. McNamara is with the Department of Dermatology at Wake Forest University School of Medicine, Winston-Salem, NC.

Disclosure: The author has no conflicts of interest to disclose.