Dr Kavanaugh, a leading Rheumatologist, provides us with the top ten topics in vasculitis from his perspective.
There has been substantial change in the nomenclature for systemic vasculitides. Wegener’s granulomatosis is now being called GPA (granulomatosis with polyangiitis) and Churg Strauss syndrome is now being called EGPA (eosinophilic granulomatosis with polyangiitis). The 3rd similar systemic vasculitis is microscopic polyangiitis (MPA), which is distinct from polyarteritis nodosa (PAN).
GPA, EGPA and PAN are sometimes known as ANCA associated vasculitides because of their potential association with anti-neutrophil cytoplasmic antibodies (ANCA).
In addition to vessel size and ANCA, other factors relevant for vasculitides include the extent of involvement (limited vs diffuse) and the response to treatment.
Systemic Vasculitis can have diverse manifestations. The skin is involved in approximately 40-65% of patients with GPA, EGPA, MPA and PAN.
Internal organ involvement can be severe and serious and affect multiple organs. However, most areas of involvement will be apparent with only a directed history and physical examination, and a few straightforward laboratory tests and imaging procedures.
ANCA testing can be of value, but results MUST be interpreted in the correct clinical context. The quality of the lab is very important.
ANCA testing should not be relied upon as a predictor of disease activity for individual patients.
Treatment options for systemic vasculitides include methotrexate for many more limited disease manifestations, and cyclophosphamide for more severe disease. Treatment often must be continued to prevent relapses.
Rituximab has gained increasing attention as an effective therapy for severe systemic vasculitis.
There are mimics of vasculitis that clinicians should be aware of.
https://mauiderm.com/wp-content/uploads/2013/10/Kavanaugh-Photo.jpg520782Maui Derm Newshttps://mauiderm.com/wp-content/uploads/2013/04/MD-WebLogo.jpgMaui Derm News2014-01-29 09:37:222014-02-20 17:53:48Top 10 Topics in Vasculitis from a Rheumatologist’s Perspective
In this presentation, Drs Bhatia and Rosen bring us the latest information on drugs that are, or will be available to the practicing dermatologist.
Apremilast is an inhibitor of PDE4 and is currently in phase III trials for ankylosing spondylitis, psoriasis, and psoriatic arthritis along with orphan status for Bechet’s disease. A published case report for apremilast for lichen planus (Paul et al. JAAD, 2013) demonstrated that 30 percent of the patients experienced a 2-grade improvement. This study was, however, small in numbers, treatment time and dosages.
As Dr Tsao mentioned in his presentation, omalimuzab has demonstrated promising results for the treatment of chronic idiopathic urticaria.
Dr Bhatia commented on the new treatments for onychomycosis, and feels that we have a “flood year of antifungals this year.” What we need to know:
Naftifine 2% gel—tape strips show stratum corneum residual after 4 weeks
Luliconazole is approved
Efinaconazole and Tavaborole are not
Itraconazole 200 mg tablets with new dosing protocol
Ketoconazole gel (Xolegel) and Itraconazole tablets (Onmel) are back
Econazole Foam is coming
In a Phase II study of luliconazole cream 1 percent for the treatment of interdigital tinea pedis, the researchers found that complete clearance was 26.8 percent and 45.7 percent in subjects in the two-week and four-week treatment group, two weeks post-treatment. Four weeks post-treatment complete clearance rates were 53.7 percent and 62.9 percent, respectively. A phase II study of efinaconazole for toenail onychomycosis also demonstrated favorable efficacy. Tavaborole, representing a new class of anti-fungals, met all primary and secondary endpoints in the treatment of nail fungus when compared to ciclopirox lacquer.
Ketoconazole gel 2 percent has the same side effect precautions as oral products, on label, but these are doubtful. It’s important to remember that the brand name in some markets may be cheaper than the generic. Also of importance, rates of mycological cure and effective treatment (secondary efficacy endpoints) were observed in the Econazole Nitrate Foam 1% group relative to the Foam Vehicle in both phase 3 studies (P<0.001). Itraconazole (200 mg) (OMNEL) is available with a new dosing protocol. In a study, 200 mg tablets were found to be noninferior to itraconazole 100-mg capsules at 52 weeks. The safety profile of Omnel is not statiscially different from that of itraconazole.
Dr Rosen began his section of this presentation discussing Pliagils (Lidocaine 7% + Tetracaine 7% Cream). Pliaglis is a topical, local analgesia for superficial dermatological procedures. It is applied 20-30 minutes for most minor procedures and 60 minutes for more major procedures and is available in 30,60 and100gm tubes.
Sitavig (acyclovir 50mg Buccal) is indicated for recurrent oro-labial HSV. The technology is a natural polymer derived from milk which adheres to the mucosa; therefore leading to high local drug concentration, but minimal blood levels. It is one tabe, applied within one hour of prodrome onset and reduces the duration of an attack by 0.5 days based upon a randomized controlled trial of 775 patients. Another advancement includes the approval of carbinoxamine maleate susp (Karbinal ER), which is a mildly sedating H1 antihistamine in an extended release formulation. It is used for the treatment of allergic rhinitis and conjunctivitis, uncomplicated urticaria, angioedema, and dermatographism. Aurstat Anti-itch hydrogel was also approved in early 2013 to treat the symptoms of atopic dermatitis and various dermatoses.
Old Drugs, New News:
Adapalene/BPO 1.2%/2.5% (Epiduo®)
Now FDA approved down to age 9
Desoximetasone 0.25% (Topicort®)
Now available as a spray
Ketoconazole 200mg tab (Nizoral®)
Severe limitations on use due to liver and adrenal toxicity, as well as drug interactions
Certolizumab pegol (Cimzia®)
Now approved for psoriatic arthritis
In conclusion, clinicians should pay special attention to the Nizoral FDA warnings published in July of 2013. (www.fda.gov) If you use it and there is any hepatotoxic event, that could cause a great problem as a practitioner.
In summary, the dermatology landscape is continuing to grow with promising new drugs and it is imperative to stay on top of the latest data.
Remember that acne can be categorized by age, i.e., neonatal (0-6wk), infantile (0-1), mid-childhood (1-7), preadolescent (7-12), and adolescent (12-19). Dr Eichenfield emphasizes that for dermatologists, mid-childhood (age 2 – 7) acne is the most worrisome. It can be associated with premature adrenarche, Cushings Syndrome, CAH, gonadal/adrenal tumors, and precocious puberty. Mid-child acne is very uncommon and dermatologists may want to consider a referral to an endocrinologist. 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.
What do the new guidelines say?
These guidelines were developed by the American Acne and Roseacea Society and endorsed by the American Academy of Pediatrics, which is the first time that the Academy has a set of guidelines for the management of acne. One of the main reasons this was done was to address the gap between pediatric dermatologists and pediatricians. It’s important to know that pre-adolescent (7 ≤ 12 years) acne is common and may precede other signs of pubertal maturation. Work-up beyond history and physical is generally unnecessary unless there are signs of androgen excess, polycystic ovarian syndrome, or other systemic abnormalities. There is evidence that acne, and possibly puberty, are now occurring at an increasingly earlier age.
A recent analysis of the National Ambulatory Medical Care Survey (NAMCS) database assessed trends in the age of children seeking treatment for acne. NAMCS data from 1979 through 2007 were analyzed for all physician visits in which acne vulgaris was listed as a diagnosis in children aged 6 to 18. The analysis revealed a significant decrease in the mean age of children seeking treatment for acne over this period.
Over the past several years, clinicians have noted an earlier onset of acne—that is, the appearance of acne in patients as young as 8 or 9 years. Indeed, it has been suggested that 12 years of age should no longer be considered the low end of the “normal” range for the onset of acne.
Acne may be the first sign of the onset of puberty in children aged 7 to 11 years. The general clinical impression of earlier puberty is, in fact, supported by epidemiologic data in the US and elsewhere. In general, the trend toward earlier puberty is stronger among girls than among boys. In any event, the earlier onset of acne has mirrored the downward trend in puberty timing.
Acne Guidelines: Highlights
Topical retinoids 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 ages. It is important to remember that topical antibiotics are not recommended as monotherapy and if a topical antibiotic treatment is to be used for more than a few weeks, topical benzoyl peroxide should be added, or used in combination products. The guidelines also suggest that fixed-dose combination topical therapies may be useful in regimens of care for all types and severities of acne. With regards to oral antibiotics, they are appropriate for moderate to severe inflammatory acne vulgaris at any age. Tetracycline derivatives should not be utilized in children 8 years of age and below. Second generation tetracyclines are sometimes preferred to tetracycline because of ease of use, fewer problems with absorption with food and minerals in vitamins and other supplements, and less frequent dosing. It’s very important that patients are educated and monitored for potential adverse events when utilizing oral antibiotics for acne. Combined oral contraceptives may also be useful as second-line therapy in regimens of care in pubertal females with moderate to severe acne; however, tobacco use and family history of thrombotic events should be assessed. Due to concerns about growth and bone density, many recommend withholding OCs for acne until one year after onset of menstruation. Isotretinoin is recommended for severe, scarring, and/or refractory acne in adolescents and may be utilized in younger patients. Remember that extensive counseling, particularly regarding the avoidance of pregnancy, as well as careful monitoring of potential side effects and toxicities, is recommended.
In this first presentation at MauiDerm 2014, Dr Tsao, a leader in Dermatology, provides us with an update on the latest hot topics in the field.
Melanoma
Dr Tsao begins with a short case study of a 45 year old man who presents with:
SSM- 0.80mm/Clark level IV
Mitotic rate: 2 per mm2
Lymphovascular invasion
Ulcerated
TILs present
As a dermatologist, would you recommend a sentinel lymph node biopsy? According to Dr Tsao “there has been a shift in the utilization of sentinel lymph node biopsies.” Han and colleagues conducted a study with a large data set of patients (N = 5,125) with sentinel lymph node biopsies and found that in patients with thin melanomas, thickness and ulceration are the most predictive features of a positive sentinel lymph node. This report can be found in the Journal of Clinical Oncology.
Dr Tsao’s key takeaway messages:
Among thin melanomas, increasing thickness and ulceration most predictive of positive nodal status
Rate is still low (~5%) and survival high (91% positive)
MSLT-1 OS: 90% negative vs. 72% positive
Among patients with 0.75mm/ulcerated lesions, if knowing the difference between 91% and 98% 5-year survival is important, then SLNB is reasonable
Cellulitis
A recent study from the New England Journal of Medicine looked at the use of penicillin for the prevention of recurrent leg cellulitis. The researchers found that prophylactic penicillin (250 mg p.o. BID) reduced the risk of cellulitis recurrence by approximately 50 percent. The duration of the benefit; however, is still unknown. Future studies for penicillin-allergic patients and cost effectiveness need to be performed.
Kidney Transplant
A report by Verneuil and colleagues found that in kidney transplant patients, donor kidney cells have been found in squamous cell carcinoma. SCC arising in kidney transplant patients. In another report by Xiao and colleagues, who looked at 69 studies which reported 104 donor transmitted cancers, they found that renal cell cancer, melanoma, and lymphoma were the most common. The cancer was usually diagnosed within one year from transplantation. For most non-renal cancers, cancers are metastatic at the time of diagnosis. Additionally, immunosuppression is stopped in most instances.
What are Dr Tsao’s key takeaway points?
Although rare, secondary malignancies from kidney transplants have been reported
Provides biologic evidence of secondary metastases
Renal cell cancer, melanoma and lung cancers may be most common- could be reporting bias since they may most likely cause death
Recent malignancy is an absolute contraindication for organ donation
Remember that a solid metastases can create another metastases from a different host.
Basal Cell Carcinomas (BCCs)
According to a 2013 study by Erits and colleagues, topical imiquimod five times a week for six weeks exhibits the greatest efficacy against BCCs. This was a single-blind, non-inferiority, randomized controlled trial looking at photodynamic therapy (PDT) versus topical imiquimod versus topical fluorouracil for the treatment of superficial basal cell carcinoma. The researchers found that imiquimod appears to be superior to PDT in efficacy but also appears to be associated with more side effects and 5-FU was intermediate in terms of efficacy and side effects. Of note, the limitations of the study include short follow-up times (12 months) and lack of cost-effectiveness analysis.
GNAQ
Shirley and colleagues reported, in the New England Journal of Medicine, that an activating mosaic mutation in GNAQ (R183Q) is associated with anomalous skin and brain tissue in Sturge-Weber Syndrome. Its important to know that the variant is not as biochemically activating as the Q209 mutation observed in ocular melanoma. The R183Q variant occurs in 0.7 percent of the general population as a germline variant. Definitive proof of this mutation requires functional verificaton, e.g. model systems.
Spitz Tumors and Spitzoid Melanomas
Recently, Weisner and colleagues found that kinase fusions are frequent in Spitz tumors and spitzoid melanomas. We know that molecular diagnostics are continuing to advance and the paucity of point mutations that are identified in spitzoid neoplasms could be accounted for by gene translocations. Remember that pediatric tumors may be more susceptible to translocations while adult cancers may reflect accumulation of carcinogen-mediated point mutations. Kinase fusions offer new opportunities for treatment, though the market for metastatic spitzoid melanoma is small.
Urticaria
Let’s consider a 35 year-old woman who has had a three-year history of chronic urticaria. A 2013 study demonstrated that omalizumab reduces
https://mauiderm.com/wp-content/uploads/2013/10/Hensin-Tsao-Photo-e1665435947736.jpg12011201Maui Derm Newshttps://mauiderm.com/wp-content/uploads/2013/04/MD-WebLogo.jpgMaui Derm News2014-01-28 07:24:342014-02-20 18:03:02Dermatology Year in Review: 2013
On Day two of MauiDerm 2014, our panel of experts in the field of Acne presented new insights and new data that may help the practicing dermatologist improve the overall outcomes of patients in their practice.
Isotretinoin Issues
Written by Judy Seraphine
Dr Guy Webster lead off the discussion by discussing some of the hot papers in acne in 2013 that help with either the understanding of acne or the treating of it. The first paper, published in JAMA Derm, discusses high dose isotretinoin and whether or not it is safe and effective. Traditionally, data demonstrated that the 120 mg/kg dose has a 20% relapse rate. One thing that we have figured out is that if someone has really bad acne as a child, they will most likely have a relapse later and likewise, patients who had really severe acne on isotretinoin will likely relapse. Two recent studies showed that the more accutane than we typically use may decrease the relapse rate. Another paper, a retrospective study, looked at patients on a really, really high dose isotretinoin versus those on high dose isotretinoin and the researchers found the really high dose had a lower relapse rate, but it was still somewhat high. As dermatologists, we have to consider that there may be a difference in how we define relapse and prospective head-to-head studies need to be done.
Another paper, published by Drs Webster and Leyden in the JAAD, looked at a new form of isotretinoin that doesn’t require a dietary adjustment. We have known for years that isotretinoin requires a fatty meal as there is decreased absorption on an empty stomach. Dr Webster feels that the most common cause of isotretinoin resistance is due to patients taking the drug on an empty stomach. Data exist demonstrating that high-fat meals enhance the absorption of the drug, yet this new form of isotretinoin may be a viable alternative with regards to dietary change and acne outcomes.
What about P. Acnes? Dermatologists should remember that there are many strains of P. Acnes that have subtle differences, but there was no difference in where they developed. A recent paper reported that they found two strains of P. Acnes. The type 1a strain of P. Acnes predominates in inflammatory acne lesions and 1b in non-inflammatory. Some strains are associated with inflammatory acne; however, this association is a trend and not an absolute. The question is whether this is due to ecology or virulence? There are two possibilities: 1a is more pathogenic and can survive better in an inflamed mileu. It’s important to look at how strain 1a is different from strain 1b.
https://mauiderm.com/wp-content/uploads/2013/04/MD-WebLogo.jpg00Maui Derm Newshttps://mauiderm.com/wp-content/uploads/2013/04/MD-WebLogo.jpgMaui Derm News2014-01-28 07:17:042014-02-01 09:41:34Acne: Part 1
Dr. Gold spends a lot of his time in Asia and, in this presentation, he shares some of the knowledge that he has acquired overseas with regards to toxins. The neuromodulator market is huge and the global medical aesthetic market is expected to post growth of 10.8 percent per year from 2010 to 2015.
Medical Insight, Inc. “Global Aesthetic Market IX Research Report April 2011”, “Facial Injectables Report July 2011” ,“EU Facial Injectables Report July 2011
As mentioned in Dr Cohen’s presentation, it is extremely important to remember that the goal, when using neuromodulators, is a natural and relaxed look for your patients.
Data on Neuromodulators
When looking at the Xeomin clinical trials, dermatologists should remember that responders at maximum frown at day 30 had to have an improvement of two points on a four-point Frown Wrinkle Scale (FWS) compared to baseline by both the investigator as well as the patient. Neither Botox nor Dysport required assessments by both parties. So while the data on the 2-point responders did not look quite as compelling, the numbers for the 1-point responders appeared good.
Mentor, which was purchased by Johnson & Johnson, has completed their clinical trials on a new botulinum toxin, PurTox. Many are hopeful that J&J will submit this data to the FDA in which case we will see this product at some point in the future. Of note, both Xeomin and PurTox are pure toxins. Whether that actually makes a big deal clinically, Dr Gold does not think so; however, it is a wonderful marketing point.
Medy-Tox , which was purchased by Allergan in 2013, is the company that developed a product called Neuronox. It is currently approved in South America and Korea for blepharospasm and tortilcollis. Dr Gold and others feel that Neuronox will not come to the United States market anytime soon. A double-blind, multi-center trial of 173 patients compared Neuronox to Botox in patients with hemifacial spasm. The efficacy evaluation was similar between both groups. A recent clinical study demonstrated the proven efficacy and safety of Neuronox on glabellar frown lines.
Another Korean company, Hugel, makes Botulax. Dr Gold mentions that this company is at many of the meetings to which he goes and they claim to have the Korean version of an FDA approval.
ChinaTox is a product made by Lanzhou Biological Products Institute. It is important to know that many of the other toxins are actually fake ones. An open label study between Botox and ChinaTox looked at 785 patients with focal spasm and dystonia. They found that ChinaTox was less powerful than Botox; therefore, higher doses were required. There were also five cases of skin rashes seen in the ChinaTox group. ChinaTox is; however, cheaper than Botox. Of note, the strain of clostridium botulinum type A was donated from the University of Wisconsin to Dr Yinchun Wang. ChinaTox was approved in China in 1989 and by 2002 the drug has been exported to several foreign countries and is currently in Brazil for both clinical and cosmetic use. ChinaTox has several different names in other countries. This is important to keep in mind as you’re reading various pieces of literature.
Prosigne-Brasil
Redux-Peru
Lantox-Russia
Lanzox-Indonesia
ChinaTox demonstrates similar efficacy as far as other neuromodulators. In Asia, calf hypertrophy is an issue. ChinaTox has shown positive benefits when injected into the calf muscle.
In Russia, there is a toxin, Relatox, with the “Russian FDA-approval.” It was produced at the Federal State Unitary Enterprise Research-Division of Microgen of Russian Ministry of Health. It is available in two dosages, 50µ and 100µ. Relatox is indicated for blepharospasm, cervical dystonia, and facial wrinkle correction and is recommended only for adults. A published article claims that Relatox is comparable to other toxins.
A topical toxin has been developed by Revance using a proprietary platform that enables transcutaneous flux. The first commercial applications will be topical BoNTA in lateral canthal lines and hyperhidrosis. The product is well tolerated and demonstrates up to 89 percent response rate. The median duration of effect is 113 days.
In the US, Myoscience is developing a hand-held medical device for the treatment of facial wrinkles. Essentially, the device uses cold-induced modulation of facial nerves. This has demonstrated promising results in difficult patients and is a new option for toxin-averse patients.
Clinical Pearls
Physicians should only use branded products that are FDA-approved in the US or CE marked in Europe, or products that have received regulatory approvals in your country. There have been instances in the US where non-approved Botox was used and patients ended up paralyzed in the hospital. Physicians are also subject to major sanctions, fines, loss of license, etc. There are many fake products out there….this important to keep in mind as there are serious issues involved with the use of unlicensed botulinum toxins.
https://mauiderm.com/wp-content/uploads/2013/10/Michael-Gold-Photo.jpg1038819Maui Derm Newshttps://mauiderm.com/wp-content/uploads/2013/04/MD-WebLogo.jpgMaui Derm News2014-01-08 11:34:422014-02-20 17:57:16Toxins: What’s New, Are There Differences Among Toxins, and What We Have Learned
In this presentation, Dr Cohen, a leader in aesthetic dermatology, discusses where we are right now in terms of botulinum toxin. Currently, there are three FDA-approved botulinum toxins type A; these are Botox (Allergan), Dysport (Medicis/Galderma), and Xeomin/NT201 (Merz). Neuromodulators that are on the horizon include PurTox, Neuronox, and China ToxThe three approved botulinum type A products are approved for the use of glabellar lines; however, they are used off-label for other aesthetic purposes.
All three products contain a core neurotoxin protein (150 kD BoNT/A), this is where the mechanism of action lies. Botox and Dysport are wrapped in protein, which is part of the neurotoxin complex Xeomin, however, lacks these accessory proteins.All three products have demonstrated efficacy and have established good safety profiles.
Xeomin
Xeomin has both medical and aesthetic studies. In 2005, Benecke and colleagues published a double-blind non-inferiority trial of 463 patients comparing Xeomin to Botox and concluded that Xeomin is at least as effective and safe in treating cervical dystonia as compared to Botox. Of note, one of the criticisms of a non-inferiority trial is that it utilizes two timepoints, and you don’t know where the subsequent timepoint ends.
In 2006, Roggenkamper and colleagues published a double-blind, phase III trial comparing the efficacy and safety of Xeomin with Botox in patients with blepharospasm. No significant differences were found between the formulations and the non-inferiority of Xeomin compared to Botox was concluded.
It is critical to understand the changes and differences in the FDA requirements in the studies for neuromodulators. When Botox was approved, a one-grade improvement was required. With Xeomin, a two-grade improvement was required. This is an important concept to keep in mind when looking at responder rates over various studies.
Two recently published, identical randomized, double-blind, multi-center, placebo-controlled trials looked at 547 patients. 366 patients received 20µ Xeomin and 181 patients received placebo. Success was defined at a two-grade improvement on a four-point scale. The median onset of effect occurred within seven days after injection and the duration effect was typically up to three months. Single and repeat treatment was well-tolerated. The majority of adverse events were mild or moderate with headache being the most common. There was a 0.2 percent incidence of blepharoptosis following a single treatment.
Sattler, et al published a non-inferiority trial comparing Xeomin to Botox in the treatment of glabellar frown lines. The independent rater and patient assessment among both products were very similar at weeks four and 12. Because this was a non-inferiority study with two timepoints, you can miss the “duration of efficacy” and the “waning effect.” The authors concluded that Xeomin is equally as effective as Botox and both preparations were well tolerated.
A small study of 21 patients by Prager and colleagues compared Xeomin to Botox for the treatment of Crow’s feet. Both products demonstrated high efficacy and good tolerability at a dose ratio of 1:1 with no statistically significant differences between the two. Also of note, the high response rates observed after four months suggest a good effectiveness beyond this observation period.
Conversation Ratios
It is important to remember that the three neuromodulators approved for aesthetic use are separate products; therefore, there is no TRUE or EXACT “conversion ratio”. Dr Cohen emphasizes the importance of learning how to use each product differently in clinical practice. The injection techniques are similar; however, there are no direct specific conversion ratios. Regulatory agencies around the world have recognized that these are different products, and there is no interchangeability among botulinum toxin neuromodulators.
Controversies
It is also important to keep in mind that combination same-syringe delivery (e.g. botulinum toxin-A and hyaluronic acid filler ”mixed together”) can be imprecise on many levels from not uniformly mixed to potential unintended spread of one of the agents.
Another big controversy is that of zinc supplementation on botulinum toxin treatments. A publication in 2012 advocated a proprietary zinc formulation to “extend the durability of botulinum toxin” and “make non-responders, responders.” Dr Cohen found that there were HUGE problems with this study. Zinc deficiency does not seem to be an issue with healthy aesthetic patients, and the article assumes that basically everyone is zinc deficient. Another major issue with this study is that the only physician who injected the product has a financial interest in the product, identified all of the patients for the study, and was an active participant in the study design. In summary, the effect of zinc supplemation with a phytase has yet to be clearly elucidated.
Dosing
When looking specifically at dosing, aesthetic physicians have historically used high-dosages in the forehead, which often caused them to look completely “flat”. “It is important to understand the importance of achieving a relaxed and natural look. Over the years, Dr Cohen and many colleagues colleagues have found that they can basically cut the forehead dose in half. This helps in achieving a natural look, softens the musculature and maintains brow shape and positioning, which is very good for patients. There are published consensus statements and recommendations on how much product to use and how best to use it for each of the products available.
Botulinum Toxin has also shown to improve facial wound healing. Dr Cohen has incorporated its use when performing Mohs closure. This leads to less tension in the scar; therefore less scar spread and a better overall aesthetic look through “chemo-immobilizaton” (Mayo 2006, Flynn 2009)– similar to what has been described peri-procedure with peri-ocular resurfacing (Carruthers) and peri-oral resurfacing (Kadunc).
Dueling
There are many attempts in the literature to try to compare the various neuromodulators. This started from an article published in 2008 in the Journal of Cosmetic and Laser Therapy looking at patient satisfaction with different botulinum toxin type A formulations in the treatment of moderate to severe upper facial rhytids. The patients were switched from Botox to Dysport and, by and large, the patients wanted to go back to Botox. Unfortunately, when studies like this are introduced, Dr Cohen comments that there is a tremendous amount of bias. Often time we see “novelty bias.” Patients return after a second injection and they don’t see the “wow” effect, and there could be “recall bias” as well in trying to remember the effect of the first treatment versus subsequent treatments.
Onset and Duration
The original Dysport trials demonstrated that median time to onset ranged from two to four days. This data; however, was not captured in the original Botox trials. A subsequent JDD trial did actually capture the effect of Botox starting to “kick-in” within the first few days as well.
It is imperative that clinicians be critical of study designs when they are comparing these various products. A meta-analysis looked at the Botox duration effect in the treatment of glabellar lines. Overall, the effect was about four months in 50 percent of patients.
Repeat injections in the same area tend to extend the duration of the product. This has been demonstrated in several studies among all three of the approved neuromodulators.
Summary
Overall, we have good safety and efficacy data among these three products demonstrating that people respond and seem to have better self-esteem (Dayan). Data suggest that, overall, patients look and feel better.
In this presentation, Dr Tsao discusses fractional resurfacing and its efficacy in clinical practice. A lot of information has become available to clinicians regarding improving the aging process for their patients. Fractionated resurfacing technologies have been designed to provide benefits for many aspects of aging by taking the best of the ablative and non-ablative technologies. In comparison to other non-ablative technologies, fractional non-ablataive resurfacing demonstrates greater efficacy. It is important to remember that fractional resurfacing is safer for non-facial areas.. It is also safer for darker skin phototypes. , Fractional resurfacing demonstrates a safer side effect profile when compared to traditional ablative devices.. The recovery time is markedly reduced and there are no permanent lines of demarcation to date.
There are a number of fractional technologies available; however, dermatologists should remember that there is not one particular laser that can target all of the concerns regarding photoaging. When you are thinking about these devices, you need to consider what you are actually trying to target. Dr Tsao comments that the ultimate goal in fractional resurfacing , is to create a localized thermal injury. Thermal injury is thought to be the key for tissue repair. Heat-induced inflammation results in immediate collagen shrinkage and tissue contraction and, subsequently, fibroblast stimulation and neocollagenesis. This concept, Dr Tsao mentions, is very similar to the ablative devices; however, the side effects and down time are much less. There is a zone of irreversible thermal damage and its associated inflammation which must heal before re-epithelialization begins. Prolonged inflammation due to infection, hypersensitivity, or extensive thermal damage due to vigorous treatment can result in complications.
How do fractional resurfacing devices work?
As previously mentioned, there are a number of fractional ablative and non-ablative technologies available,. It is important to match treatment depth and treatment parameters with the clinical indication(s), i.e., are you targeting pigment (superficial to mid dermis), mild rhytids (mid reticular dermis), moderate rhytids (deep reticular dermis) or surgical scars, burn scars and acne scars (deep remodeling). This is the real learning curve with these devices…you need to know what you are targeting and whether or not you may need a combination of these therapies to achieve your clinical goals.
Each of the devices has a different way of administering the microthermal zones. These devices include continuous motion scanning and traditional lens array stamp pattern, which can be a little bit harder to administer because of the potential of overlap or skip regions.
Non-Ablative Fractional Resurfacing
Every pulse creates a localized injury or, microthermal zone (MTZ). You are actually creating columnated areas of heat inflammation. The depth and diameter depend on the type of device that you are using, as well as the parameters selected for treatment. The fractional non-ablative devices create the columnated thermal injury while leaving the normal intact skin in between; therefore, retaining viable stem cells in between the microthermal zones of injury. This allows for the skin to repopulate much faster, resulting a limited healing period.
Fractional non-ablative laser treatment results in complete re-epithelialization in 24 hours. In human tissue, you can see clear collagen denaturization from papillary dermis into mid reticular dermis. The healing occurs from viable tissue and the zones of spared tissue which contain clusters of epidermal stem cells and Transit Amplifying (TA) cells. What is unique about the non-ablative technologies is that they leave the epidermis intact. The downtime for most of these technologies is about three days of some redness and swelling. This is a very manageable outcome for most patients.
Dr Tsao also comments that over the past two or three years, we have been very fortunate to have a new fractional non-ablataive device available at 1927 nanometers which matches one of the water absorption peaks in the mid infrared spectrum . This wavelength absorption is stronger than most non-ablative wavelengths and weaker than ablative wavelengths. This device fulfills the role to more selectively target lentigines, pigmentation, actinic keratoses and seborrheic keratoses
Ablative Fractional Resurfacing
These devices work exactly like the non-ablative devices in that they create microthermal zones; however, the big difference is that the epidermis is shed along with a portion of the dermis. This creates more thermal damage, requiring a longer recovery time. Replacement of the skin surface requires about one week. Patients must be aware of the longer downtime with the fractional ablative devices. Ultimately, what you are aiming to achieve is a healthier more youthful epidermis and dermis.
How does this translate clinically?
If a patient does not want surgery or ablative treatment, then fractional non-ablative or ablative resurfacing could be a viable option. It is important to set realistic expectations with your patients as far as achievable outcomes. Non-ablative fractional devices will provide improvement of superficial rhytids and dyspigmentation, but not likely provide significant benefit for deeper rhytides. The fractional non-ablative devices provide marked improvement of atrophic and acne scars. The fractional ablative devices provide greater benefit for moderate to deep rhytides and dyspigmentation, especially perioral rhytids.
Downtime
It makes a tremendous difference to patients if you can have photos available to show them the expected downtime so that they can make a more informed decision regarding their treatment.
Microlaser peel- 7 days of peeling, 2 weeks of pink hue
Fractionated non-ablative
1410nm- 1 day mild erythema and edema
1550nm- 2-3 days erythema and edema
1927nm- 4-5 days erythema and edema and pinpoint crusting; 1 week of pink hue
2940nm- 7 days erythema and edema, 2 weeks of pink hue
Fractionated ablative- 1-2 days pinpoint bleeding, 7 days erythema and edema; 4-6 weeks of pink hue
Ablative-14 days erythema and edema; 2-3 months of pink hue
Clinical Pearls
When treating the eyes, you have to be extremely careful to prevent ocular damage. Less aggressive treatment is necessary to prevent ectropion formation. It is also important to use metal protective eyeshields when treating the eyelids. Proparacaine anesthesia and erythromycin ointment to coat the eyeshields can be used for lens placement. It is also important to use particular caution in patients with prior surgical procedure history, such as a prior facelift or blepharoplasty, as the facial anatomy may be altered .
With regards to darker skin phototypes, less is more (fluence, density, passes). You may want to consider a laser test site. You should also stress the need for strict photoprotection and discuss the increased risk for PIH. , You may consider pre-treatment use of retin-a or hydroquinones. You should also use greater cautionwhen using ablative fractional devices, as the risk of side effects is greater.
Remember that when you apply these treatments to non-facial regions you have to be very cautious as there are not as many pilosebaceous units to assist in re-epithelialization, resulting in an increased risk of scar formation when treating these areas with both fractional non-ablative and fractional ablative devices.
https://mauiderm.com/wp-content/uploads/2013/12/sandytsao.jpg145135Maui Derm Newshttps://mauiderm.com/wp-content/uploads/2013/04/MD-WebLogo.jpgMaui Derm News2013-12-28 22:08:332014-02-20 17:59:11Fractionated Laser Technologies: Just the Fracts…
The tattoo removal market is projected to grow significantly in North America. In 2004, there were 19,900 tattoo removal procedures at an estimated cost of $5.9 million and by 2009 there were 33,900 procedures estimating $14 million demonstrating a 21 percent increase in the market. There are two major market drivers for the procedure, the first being tattoo popularity. A study at Northwestern University published in the JAAD in 2006 reported that 23 percent of people in the United States have at least one tattoo (69,000,000 people). This was a 30.4 percent increase over the 2003 Harris Interactive study that reported that 16 percent of the US population had at least one tattoo. The second market driver is “buyers remorse” coming from “tattoo regret”-driven by changes in life and/or circumstances. “Tattoo regret” ranges from a reported 15 to an estimated 50 percent of tattoo wearers.
There are multiple, low-cost treatment options for tattoo removal. These include:
Cryogenics, i.e., cryotherapy
Acids of various kinds
Topical retinoids
Hyfercation
Continuous Wave Lasers
Bleaching agents
Surgical excision
Abrasives with or without chemicals
Dermabrasion or salabrasion
However, these methodologies come with many complications such as scars, permanent pigmentation changes, residual tattoo pigment, wound infection, ineffective overall treatment, and can be a painful and slow process.
Laser Tattoo Treatment
There are several advantages to laser tattoo treatment. It is a non-invasive procedure with less pain that produces optimal clearing. With laser treatment, there is a lower risk of scarring and reduced hypo-pigmentation. There is also no change in skin texture, minimal post-operative care and the healing usually takes about one to two weeks. However, there are disadvantages to laser treatment. Pain is the number one issue (it hurts a lot more to remove a tattoo than to get one), but topical and injected analgesia can be used in conjunction with the laser. Realistically, it is important to let customers know that as many as 10-15-20 treatments may be required to “satisfactorily” remove a single tattoo (the tattoo will lighten 30-50 percent with each treatment). It is extremely important to set appropriate expectations with you customers and their patients. The treatments can result in hypo-pigmentation, routinely resulting in redness and swelling and punctate bleeding is also a possible (but “normal”) side effect.
As with ANY laser treatment, other more serious side effects are also possible, including–hypo-pigmentation, burns, blisters & scarring.
Pigmented Lesions
The market for pigmented lesion removal is also projected to grow significantly in the coming years. These lesions include epidermal lesions (sun spots, age spots, and melasma) as well as dermal lesions (nevus of Ota/Ito and blue nevi).
Treating Pigmented Lesions with Lasers
Dr Gold comments that both the alexandrite 755 nm lasers and the Nd: YAG 1064 nm lasers are both effective lasers for pigmented lesions. There are several advantages to treating pigmented lesions with lasers, these include the fact that it is a fast procedure; it is a simple treatment technique with minimal discomfort. DCD may or may not be required, depending on the device being used. It usually requires one to four treatments and the lesions darken for five to ten days before they exfoliate. There is improved efficacy with laser treatment because of the thermal effect and the photoacoustical effect.
Several lasers exist for the treatment of both tattoos and pigmented lesions. For pigment, long-pulsed alexandrite lasers are good; Q-Switched lasers are the treatment of choice for tattoos and most pigmented lesions. It is important to remember that tattoos should NOT be treated with IPLs. Recently picosecond lasers have become available which show, in clinical studies, reduces the treatment time for the overall improvement of tattoos.
R20 Tattoo Removal
R20 involves performing three to four laser treatments in one session. The result of the R20 method is 50 to 85 percent clearing in a single session without any additional side effects. Laser Tattoo removal treatments form tiny vapor bubbles in the skin (frosting) that looks like fine white powder. Ordinarily, this frost refracts the laser beam preventing it from penetrating the skin. After 15 to 20 minutes, the frost disappears making it possible to do another treatment or “pass”. Dr Gold states that the R20 Tattoo Removal method simply waits for this to happen and lets us treat clients three to four times in one visit. Combining three to four laser tattoo removal treatments during one office visit lets the laser reach deeper than with a traditional single-pass treatment. One R20 treatment would be sufficient to completely remove an amateur black tattoo or for lightening a tattoo for a new one. For professionally applied black tattoos however, about 50 to 75 percent fading will occur. This is significantly more fading than expected from three to four conventional treatments. Using the R20 method will cut the total time for removal by half or more.
Conclusions
In conclusion, we know that 25 million people in the US have a tattoo. There are 250,000 women being tattooed each year. Approximately 50 percent of people who have a tattoo look to have them either removed or augmented. The average age of procuring a tattoo is eighteen, often leaving the tattoo as a permanent reminder of their poor decision to get one in the first place. A clinical pearl that Dr Gold tells all of his patients is that it costs more money to remove a tattoo and it hurts more to remove a tattoo then it does to get one.
In this section, Drs Frieden and Friedlander reviewed coxsackie onychomadesis, the treatment of onychomycosis in children and a how to best obtain nail specimens in kids.
Healthcare providers should be aware that onychomadesis is a sequela of HFMD and fairly commonly seen after coxsackie A-6 infection. With onychomadesis, you typically see shedding of the fingernails and toenails within one to two months after HFMD. Onychomadesis can appear in the form of exaggerated Beau’s lines. It is not surprising that this happens with infection, but why can it occur with mild disease? Osterback R et al obtained shed nails from two siblings with onychomadesis who had HFMD eight weeks before the nail shedding. The nail clippings were enterovirus positive by RT-PCR and one case was identified as CVA6. Dr Frieden believes that this may, in fact, be an infection of the nail matrix and not merely a physiological response of stopping nail growth.
Onychomycosis
Fungal nail infections are more common in adults; however, they DO affect children (0.16%). The incidence of fungal nail infections in children may be increasing due to occlusive foot lifestyle. While families want their children to be “perfect”, they are reluctant to put their children on prolonged systemic therapy, and do they want their children to undergo lab studies. It is important to keep in mind that children have thinner nails and; therefore, grow faster.
How do we best approach fungal nail infections in children? A study by Lawry MA, et al. showed that the best approach to diagnosing fungal nail infections is through PAS and culture and the second best approach is PAS.
Clinical Pearl: Dr Frieden comments that one of the best ways to get a diagnosis of onychomycosis in a small child is by using a disposable curette. Kids are not as afraid of this versus a scalpel because this instrument is blunt and looks more like a spoon. This is a great technique for a KOH or culture specimen.
How do we treat children?
Benign neglect (this is certainly still a reasonable approach)
Ciclopirox, amorolfine lacquer, bifonazole-urea
Griseofulvin 20/kg for at least 6 months; don’t exceed 1 gram (compliance can be difficult as well as side effects)
Terbinafine 5mg/kg/d don’t exceed 250mg; FN 6 wks; TN 12 wks (Families can get a month supply for $3-$6)
Fluconazole 6mg/kg/week once a week; FN 12 weeks; TN 26 wks
Dermatologists should know that onychomycosis does not always require systemic treatment for a cure. Dr Friedlander and her colleagues conducted a prospective trial of forty children with non-matrix nail disease. 30 patients (25 male and 15 female with a median age of 9.8) were placed on active topical ciclopirox lacquer and 10 patients on vehicle. The lacquer was applied daily and nails were trimmed weekly for 32 weeks. If the patients had a poor response, they were rolled over to active treatment at week 12. The only known AE was a transient discoloration of the nail.
The graph above shows that 77 percent of these patients had mycologic cure, 71 percent had effective treatment and 34 percent had a complete cure. These numbers are much higher than what we see in adults. These patients were followed over one year and the vast majority of them did not relapse. When asked about quality of life and whether or not the patients would undergo this treatment again, over 90 percent responded “definitely yes” or “probably yes.” (Friedlander SF et al. Ped Dermatology. 2012;Dec28)
This trial was just a a small pilot study, and thus needs to be repeated. Non-lunula nail disease can remit without medication (n =2); and topical therapy appears to work better in young nails than in adult nails. This data suggests that topical therapy may be a reasonable option as first-line therapy for some children with fungal nail disease.
There are new products currently being studied for the treatment of nail disease. Nuvail, for example, is an innovative approach in that it is a poly-urethane vapor permeable substance. It is currently marketed for dystrophic/brittle nails. A small prospective study of Nuvail in 62 patients demonstrated 60 percent improvement in six months and a 62 percent mycologic cure in six months. Stay tuned for more information….
https://mauiderm.com/wp-content/uploads/2013/04/MD-WebLogo.jpg00Maui Derm Newshttps://mauiderm.com/wp-content/uploads/2013/04/MD-WebLogo.jpgMaui Derm News2013-12-17 11:44:032014-01-13 08:31:09Pediatric Dermatology: Nail Diseases
