Clinical Pearls: What to do with patients on systemic steroids?

At MauiDerm NP+PA Winter, Dr Zone provided the audience with some key takeaway points regarding systemic therapy….

What Does Dr Zone do with his Patients on Systemic Steroids??

Patients on systemic corticosteroids should be tested (prior) and monitored for hyperglycemia and hypertension—many patients’ blood pressure will skyrocket on systemic corticosteroids. Gastric ulcer protection may be provided with H2 blocker or PPIs as many patients will get ulcerative changes in their stomachs. These patients should be monitored every two to three weeks.

Dr Zone also utilizes osteoporosis prophylaxis for patients on systemic corticosteroids. That should include bisphosphonates, calcium calcium carbonate plus D, calcitriol, estrogen, or testosterone.  The reason for this—if you start a patient on prednisone today, there is an excellent chance that the bones will start to demineralize immediately. When prescribing corticosteroids, start high to get control of the disease or symptoms, and then begin to minimize the dose. Give entire dose in the morning or bid early in the day. Alternate day therapy prevents adrenal suppression but NOT osteoporosis.

Taper oral corticosteroids in order to avoid rebound in cases of short-term treatment….In long-term management, slow tapers are important for dealing with adrenal suppression—the last 5mg is the crucial time for coming down slowly.

What about? Intramuscular triamcinolone—Dr Zone has been using this more in his practice. He finds that the patients have fewer side effects; sometimes they have trouble sleeping.

MauiDerm News Editor-Judy Seraphine


Psoriasis: Update on Emerging Systemic Therapies

Craig Leonardi, MD

At MauiDerm 2014, Dr  Craig Leonardi, Clinical Professor of Dermatology at Saint Louis University, presented us with the latest data on emerging systemic therapies for the treatment of psoriasis. According to Dr Leonardi, “the psoriasis space is going to move very quickly over the next year/year and a half…”

Dr Leonardi comments that many of our 2nd generation biologics were developed with these cytokines in mind (see below).

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Remember that drugs come and go and many fall by the wayside; what’s important to us, as practitioners, is finding the best medicine for our patients.

Certolizumab Pegol (CZP)

CZP is a peglyated Fab fragment. It was initially approved for Crohn’s disease and subsequently approved for the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. In 2005, there was a large phase II psoriasis trial of 176 patients with 10 percent BSA and PASI 12. It was conducted in Germany and France to look at CZP for the treatment of psoriasis. There were three treatment arms: 200mg sc qeow, 400mg sc qmonth, and placebo. PASI 75 results demonstrated 75 percent, 83 percent and 7 percent, respectively. PGA results (clear-almost clear) showed 53 percent, 72 percent and 2 percent, respectively among all treatment arms. There were no unexpected safety issues. This data tell us that CZP is both efficacious and safe for the treatment of moderate to severe plaque psoriasis. The fact that it is approved for PsA is also important to patients with PsO/PsA. This data was presented in 2007 at the American Academy of Dermatology and published as a paper in 2012. It appears that currently, UCB, the maker of CZP, has again taken an interest in this medication, as there is some development effort and we should be seeing a psoriasis trial quite soon.

Targeting the IL-12/23 Pathway

Both ustekinumab (IL-12) and briakinumab (IL-23) block the shared p40 subunit. When you block IL-12, you down-regulate a set a cytokines from the Th1 pathway, including INFy, IL-2 and TNF-alpha.  When you block IL-23, you down-regulate IL-17 alpha, IL-17f, IL-6, TNF-alpha, IL-21 and IL-22.

Function of Th17 Effector Cytokines


•Expressed by memory NK and T cells

•Increased in psoriatic skin

•Subcutaneous injection à neutrophilia

•Enhances inflammation

•Enhances angiogenesis


•Expressed in high levels by Th17 cells

•Increased in psoriasis (skin and plasma)

•Levels correspond to disease activity

•Induces keratinocyte hyperproliferation (in vivo, in vitro)

•Stimulates keratinocytes to secrete antimicrobial peptides

Ustekinumab is a high-performing drug for psoriasis patients. The data at week 28 in both the PHOENIX 1 and PHOENIX 2 studies, show about 70-79% of patients are achieving a PASI 75; this is a huge achievement for these patients.

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New Development Efforts

Ustekinumab was recently approved for the treatment of PsA, based upon its efficacy data with regards to an ACR 20 response at week 24.

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However, when you compare these numbers with the other TNF antagonists, ustekinumab does not appear to work as well in PsA. It remains to see how our rheumatology colleagues will regard this drug over time. It may be used as a second- or third-line drug for PsA.

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3rd Generation Biologics

There is a down-stream effect from anti-IL-23 blockade feeding into IL-17 and down-regulating IL-22. Many pharmaceutical companies have been studying this pathway; there are two, possibly three, IL-23 inhibitors currently in trial, there are two anti-IL-17 inhibitors, an IL-17 receptor antagonist, and there was an IL-22 blocker that came and went…this is a very rich developmental pathway with many promises.

IL-17 Antagonists

The phase II studies of secukinumab (Novartis) a human IgG1 monoclonal IL-17A antibody demonstrated that the 150mg and 300mg doses were statistically significant as compared to placebo at week 12. This is an incredibly high-performance drug, i.e., in the 300mg dose, between 80 and 90 percent of these patients were achieving a PASI 75. According to Dr Leonardi, “this is absolutely remarkable when you think about the world of chronic inflammation”.

The results of secukinumab’s pivotal phase III data was released this fall at EADV.  Dr. Leonardi reported that the ERASURE study evaluated secukinumab doses of 150 mg and 300 mg in a placebo controlled study.  PASI-75 response rates in the secukinumab groups reached a peak at week 16 (80% – 90% range).  IGA scores of “clear or almost clear” were reported in the 60% to 75% of patients. Treatment benefit was maintained through week 52 on q4 week injections following an induction period. Other phase 3 trials included the FIXTURE study included etanercept as an active control.  In this comparator study patients showed a more rapid response to secukinumab vs etanercept (3 vs 8 wks) to achieve a PASI 50 and greater number of patients achieving PASI 90 (72.4% vs 41.5%). The third secukinumab Phase 3 trial SCULPTURE compared fixed-interval q4 weeks maintenance dosing with an “retreatment-as-needed” regimen. Data from follow-up to week 52 showed fixed interval therapy with SEC 300 mg and 150 mg q4wks sustained significantly greater PASI 75, 90 and 100 clearance rates over 1 year compared to “retreatment-as-needed”. “Retreatment as needed” is not a good regimen for any biologic”, says Dr. Leonardi.

We haven’t seen any of the safety results from the secukinumab phase III trials; however, the drug was well tolerated overall according to the phase II data according to Dr. Leonardi.

Ixekizumab (Lilly), is another anti-IL 17 monoclonal antibody, is another high-performance skin-clearing drug based upon its phase II data. Studies looking at 10, 25, 75 and 150 mg demonstrated that at the two highest doses, 80 percent of patients were at the PASI 75 range. There were no serious adverse events in this trial and the drug had a “remarkable safety profile” according to Dr. Leonardi.

The biostatisticians at Lilly, the makers of ixekizumab, utilized Youden’s Index to create a sensitivity and specificity assay. They determined that if they looked at the PASI 50 response at week four, they could make accurate predictions on the chances of success downstream. The likelihood of achieving PASI 75 and PASI 90 correlated with the PASI 50 response.

Brodalumab (Amgen) is an anti-IL-17 receptor antibody, which blocks not only Il-17A but also IL-17E and IL-17C.  It is another high-performance drug for the treatment of psoriasis. The phase II studies, which were completed some time ago, demonstrated positive efficacy results along with a good safety profile. The long-term maintenance of clinical response with brodalumab has been demonstrated through week 96 of an open-label extension study. The one caveat with this open-label extension study is that it is an observed analysis, not an intent-to-treat approach to the data. Remember that the patients who came out of the trial are those who are not doing well so as you move through the trial, the population will continue to improve.

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Positive results were also seen with sPGA over 96 weeks.

Interleukin 23

Remember that the p19 subunit is NOT shared; therefore, an anti-P19 molecule will block just IL-23. Tildrakizumab, a novel anti-IL23p19 monoclonal antibody, demonstrated good results in a 16-week phase IIB trial. There were four doses at weeks 0 and 4 (5mg, 25mg, 100mg, and 200mg) versus placebo.  PASI 75 was achieved in 35, 65.5, 67.1, and 76.2 percent of patients, respectively versus 4.9 percent in the placebo arm and PASI 90 was achieved in 11.9, 24.4, 38.2, and 51.2 percent of patients versus 2.2 percent in the placebo arm. Tildrakizumab appears to be generally safe and well tolerated.

Small Molecules

Apremilast (Celgene)is a novel, small molecule that inhibits PDE-4. It has a variety of immunosuppressive effects, in that it reduces TNF-alpha, IL-2, IFN-γ and several leukotrienes. In Phase III studies (ESTEEM I and II), apremilast (30 mg BID) has achieved a PASI 75 rate of 33 percent. Importantly, scalp, nail and pruritus scores were superior in the apremilast patients compared to controls. Phase III results also demonstrated greater improvements from baseline Dermatology Quality of Life Index versus placebo.  The majority of adverse events (AEs) were not serious and included mild gastrointestinal side effects: nausea 16% and diarrhea 19%.

According to Dr. Leonardi, apremilast also has phase III PsA results that are statistically significant versus placebo although not quite as robust as the TNF inhibitors.  (FDA approval for apremilast for the treatment of PsA was announced during the winter AAD).

Tofacitinib (Pfizer), a novel, oral JAK inhibitor approved for the treatment of rheumatoid arthritis, is currently being investigated as a treatment for psoriasis among other indications. At week 12, PASI 75 response rates were significantly higher for all tofacitinib twice-daily groups: 25% (2mg), 40.8% (5 mg) and 66.7% (15 mg), compared with placebo (2%). It appears to work about as good as methotrexate. Of note, in rheumatoid arthritis, the FDA approved only the 5mg dose. The phase II safety data reported five serious adverse events (SAEs), three of which (atrial fibrillation, pyelnephritis, and urosepsis) occurred in one patient on the 2mg BID dose. There was a mild increase in Hgb levels that was greater in the 15mg BID group. There was a transient decrease in PMNs in the 5mg and 15mg BID groups and there were dose-related increases in both HDL and LDL. In the rheumatoid arthritis trials, the FDA found that the numerical increase in malignancy incidence over time was of particular concern and is consistent with a scenario where increasing exposure to tofacitinib increases the risk of malignancies. The FDA also stated that opportunistic infections, including TB, were “not uncommon.” In the RA program, 14 out of 15 patients who died due to infection were on tofacitinib. There were 34 patients with opportunistic infections, all of whom were on tofacitinib. Despite the immunological differences between rheumatoid arthritis and psoriasis patients, this is remarkable data and something that we, as dermatologists, need to pay particular attention to.


In conclusion, we can see an explosion of new biologics in the marketplace with most of the drugs targeting the IL-23 pathway. We still have an unresolved issue with regards to major adverse cardiovascular events (MACE).  Some feel that there is a signal at the IL-12/23 blockade level, it will be interesting to see if the MACE signal populates the IL-17 blockers…there may be more information coming out on that.  We are also seeing a wide variety of novel small molecules demonstrating moderate to robust efficacies and the safety profiles for some of these products are promising.  There has also been a move to explore the JAK inhibitor in a topical formulation to treat psoriasis.

Psoriasis patients are now the “model” of choice for chronic inflammatory disease and we are getting these drugs earlier now than ever before.  Remember that many of the drugs have fallen by the wayside for efficacy and/or safety issues. We need to select drugs that are good for our specialty and for our patients. As dermatologists, we need to consider that short- and long-term safety issues do exist; however, the benefit/risk ratio appears to be favorable overall.

Our treatment paradigm has shifted from a stratified approach, i.e., patients must fail the previous “step” of therapy before initiating a more “aggressive” therapy to an approach whereby the choice of therapy depends upon individual patient characteristics.


MauiDerm News Editor- Judy Seraphine


Hair Today Gone Tomorrow

Jerry Shapiro, MD

Dr Shapiro, an expert in hair loss treatment, provided the audience with a practical approach to treating hair loss. Dr Shapiro practices in Vancouver, Canada and New York, New York. In Canada, he sees 60-70 patients per day and 70 percent of his patients are female. 35 percent are PHL and telogen effluvium, 30 percent are alopecia areata, and 35 percent are cicatricial alopecias.

Hair Loss in Women: Part 1

It’s important to know that at least one third of women experience hair loss and the effect of hair loss on patients’ emotions is often greatly underestimated by physicians. As a clinician, you almost need to act as a detective to find out the cause of the hair loss. It is imperative that you spend a good amount of time talking to your patients about their hair loss, trying to assess an approximate duration of time since their hair loss began. Of note, the youngest cases of MPHL and FPHL that Dr Shapiro has seen is age eight and it happens suddenly versus gradually.  Ask your patients whether or not their hair loss was sudden or gradual. Another important step in evaluating hair loss is to assess the pattern. We should all be familiar with the Ludwig classification of Female Pattern Hair Loss ranging from classes I to III. Also of importance is to address whether the hair loss is thinning or shedding. The key question for shedding is to ask “is there hair on your pillow?” and “is there hair in your food? or on the stove? Is there hair in the fridge?” Keep in mind that you need to lose 50 percent of scalp hair to notice any change clinically. So, someone who has 100,000 hairs and someone who has 50,000 hairs look exactly the same, you can’t necessarily see that clinically.

The next step in the evaluation is to determine whether the hair is falling out from the roots or whether it is breaking. Hair loss from the roots can be associated with AGA, telogen effluvium, or alopecia areata; hair breaking with tinea capitis, cosmetics/trichotillomania, or hair shaft abnormalities. A thorough evaluation also includes taking a good family history. Remember that family history includes siblings, aunts, uncles, and grandparents—not just the mother and the father. Hair care practices are also very important, i.e., how often do they go to the hair dresser, how often do they shampoo, what products do they apply to their scalp? There are sorts of hair care practices that can cause hair loss.

When talking to your female patients, you need to address any systemic illnesses, recent childbirth, recent surgery and any psychosocial stressors. Psychosocial stressors such as bereavement, break-up/divorce, and bankruptcy can initiate a telogen effluvium. New medications can initiate hair loss within one to three months. (Some of these medications include acetretin, heparin, interferon alfa, isotretinoin, ramipril, and many more.)

Factors that might indicate androgen excess and thus can contribute to hair loss include seborrheic dermatitis, acne, hirsutism, and irregular menstrual cycles. Other important questions include signs of hypo or hyperthyroidism, heavy menstruation, and a vegetarian diet.

Five Stages of the Clinical Evaluation

  1. Distribution of hair loss—where is it on the scalp? We tend to think that this is just on the top, but that’s not the case.
  2. Inflammation, scale and erythema
  3. Scarring vs. non-scarring—you may have to use your dermatoscope in order to see the ostia.
  4. Quality of hair shaft—determine how much they have grown and whether or not the hairs are broken. Are there new hairs growing in? This can tell you whether or not the treatment is working…patients like to hear that there is regrowth.
  5. Pull test—tug at 60 hours in order to see how many hairs you can get. Make sure that patients have not shampooed that day because the results can give you a false negative.

Diagnostic Tools

There are several new diagnostic tools available for the scalp and these include dermascopy (10-fold magnification), videodermascopy (50-100-fold magnification), and folliscope that magnifies the scalp 50-100 times. This can count how many hairs the patient has per square centimeter and determine how wide the hairs are. It will tell you how many microns each individual hair is and give you an average at the end. Patients really appreciate this, they see you do this in front of them and they feel that you are doing something very useful. Dr Shapiro feels that because of this, he has been able to reduce the number of biopsies because he can now make a diagnosis frequently using trichoscopy or the folliscope. Usually you want your hairs more than 60 microns in hair shaft diameter on the average, if they are less than 30 then you know there is significant miniaturization.

Hair Loss: Part 2: How does Dr Shapiro treat some of these conditions?

Alopecia in women can be categorized as Female Pattern Hair Loss, alopecia areata, and cicatricial alopecia: lichen planopilaris. In patients with Female Pattern Hair Loss, this is a crucial time to utilize the Ludwig Classification for FPHL.

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Female Pattern Hair Loss

When assessing women with Female Pattern Hair Loss, it is important to test for any signs or symptoms of androgen excess. If there are no signs or symptoms, you can determine the class of hair loss based on the Ludwig stage. If there are signs or symptoms of androgen excess, an endocrine work-up should be performed in order to rule out polycystic ovarian syndrome, some kind of adrenal hyperplasia, or another form of androgen excess. You may want to consider referral to either an endocrinologist or a gynecologist. From there, you can assess the Ludwig stage.

If the patient has Ludwig stage III, a hairpiece could be considered, as that is typically their only option.  Prices on hairpieces and wigs can vary so that is an important consideration for patients. If you think that the condition will go away, you can suggest a more inexpensive wig/hairpiece from a department store.

Ludwig stages I or II can be treated with topical minoxidil solution (5%) for one year. Topical minoxidil solution is typically used twice per day; however, there are more and more studies demonstrating that a once a day treatment of minoxidil five percent may be as efficacious as minoxidil two percent bid. Women typically do not like the morning application, so Dr Shapiro will use the 5% solution or foam.

What does Dr Shapiro tell his patients?

Dr Shapiro prefers the solution to the foam because it is more precise. He instructs his patients to make five parts and put five drops in each part and spread it with their fingers afterwards. It should not take more than 90 seconds. If a patient complains that it is taking them a long time, ask them exactly what they are doing.

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Prevention is key, there is a 65 percent chance of doing so with five percent minoxidil solution.

If there is no improvement, you may want to add:

  1. antiandrogen therapy + OCA (if childbearing age)
  2. Hair transplation if donor area dense
  3. Hair prosthesis
  4. Hair cosmetics

When it comes to antiandrogen therapy for women, Dr Shapiro uses a lot of spironolactone. He starts at 50mg twice per day for one to two months and then goes to 100mg twice per day if the patient can tolerate it. He always checks their potassium at baseline, one month, and every three months after that. Dr Shapiro also checks their sodium levels. It is important to check all of their electrolytes. There are reports of dilutional hyponatremia with spironolactone and you can end up in trouble. In the elderly population, be sure to check their kidney function as that can also be affected by spironolactone. Of note, spironolactone is approved for women whereas we don’t have a track record with all of the other antiandrogens.

With regards to Propecia (finasteride), Dr Shapiro always warns female patients that he is unsure of what it could do to the breasts, ovaries or uterus 20 to 30 years down the road. We don’t have the long-term data. We do know that it works. Dr Shapiro will use the 2.5mg per day in women; however, keep in mind that this is a Class X drug and spironolactone is a Class D drug so you must warn patients about pregnancy.

What about oral contraceptives?

The oral contraceptives can be categorized as excellent, very good, good, or bad depending on the estrogen component. Products containing drospirenone and cyproterone acetate (available in Canada and other parts of the world) are excellent choices. Very good options include those with norgestimate, desogesterol, and norethindrone acetate. Don’t stop them, because once you stop and start another you can elicit a telogen effluvium or you can unmask or accelerate their androgenetic alopecia even more. If they are on levonorgesterol (a good option), it’s fine, just leave them on it. Stopping and starting birth control pills can create havoc. Norgesterol and norethindrone are bad progestogens. If a patient is on these, Dr Shapiro will get them off of it and change to something else.

Around six months, it is important to assess patient satisfaction with the current treatment. If they are satisfied, that’s great. If they are not satisfied, you may want to consider hair transplantation if the donor area is dense. One in three women have very poor donor areas and you usually cannot do a hair transplant on them.  Dr Shapiro usually does strip harvesting in women, you don’t need to do follicular unit extraction because they usually have long hair and don’t care if they have a scar in the back; if they do, you may have to go to follicular unit extraction. For men, you want to do follicular unit extraction because they usually have short hair. For women, Dr Shapiro will take a strip usually around 15-20cm long and usually 1.3cm in width. You then stitch it up and make holes in the front of the scalp and insert them in the holes.

Alopecia Areata

As dermatologists, we are all familiar with how to diagnose and treat this condition to some extent. For centuries, non-specific crude treatment has been used to treat alopecia areata. In the 1800s, they believed that treatments that irritated the scalp seemed to work. To quote Batemen from 1817 “the more caustic a substance and the application of a blister are often extremely successful” and “ointments of oil of mace, turpentine, mustard and black pepper.” Is what they used much different from what we use now? This is how Dr Shapiro treats alopecia areata…

First of all, he looks at the age of the patient. If they are less than ten years old, he will use minoxidil 5% solution with or without a topical corticosteroid or short contact anthralin. If the patient is over ten years old, then Dr Shapiro will look at the extent of scalp involvement. If there is less than 50 percent involvement, he uses intralesional corticosteroids plus or minus minoxidil 5% solution, plus or minus a topical steroid or short contact antralin. In his practice, Dr Shapiro will use 5mg/cc of triamcinolone acetonide and a maximum of 20mg triamcinolone acetonide per month. He feels that is safe and has never had any problems over the last 25 years. If a patient has a large area to be injected, he will go down to 2.5mg/cc and there didn’t seem to be much of a difference. If you have to do the whole scalp, he will use 25mg/cc for a total of 8ccs and he will do 80 injections.

What about topical corticosteroids? A study of 28 patients demonstrated that clobetasol propionate 0.05% under occlusion was effective for the treatment of alopecia totalis/universalis. Dr Shapiro began using clobetasol on his patients and there was a difference regarding hair regrowth. Anthralin one percent for one-hour daily (many times combined with five percent minoxidil) has also shown to be efficacious.

When someone has more than 50 percent of scalp involvement, Dr Shapiro uses contact immunotherapy. He usually uses DPCP and achieves a 78 percent response rate in non-totalis/universalis, but a 17 percent response rate in totalis/universalis. There is a high relapse rate of 62 percent and only half of these patients respond to therapy. Dr Shapiro has bottles in various concentrations and sensitizes not on the arm, but on the scalp. He then applies two coats on half of the scalp initially on the anteroposterior direction, then in the lateral direction, again only on half of the scalp. Make sure that you protect yourself when it is applied because this is extremely immunogenic.

Remember that there is no cure for alopecia areata. Sometimes certain areas do not respond and you may have to combine treatments, just like in psoriasis when you may use polytherapy. Dr Shapiro will inject the areas that are not responding once a month with triamcinolone acetonide and in three out of four weeks they will get the DPCP or dyphencyprone. Dr Shapiro will do the eyebrows as well if he sees that it has worked on the scalp. Problems with this include eczema, blisters, and marked edema. Make sure that your institution will cover you in the event that there are any problems as this is not FDA-approved. Patients need to sign an informed consent. Lymph node enlargement can also occur and the safety of this is unknown; however, Dr Shapiro has never had a case of lymphoma in over 20 years. The only case of lymphoma that he ever had from alopecia areata was a patient who was on cyclosporine. When you are dealing with dark-skinned individuals, be careful with hypopigmentation. NEVER give this to a patient to take home.

If people respond, then the treatment is continued. If they don’t respond, you can consider minoxidil 5 percent solution plus or minus a topical corticosteroid or short contact anthralin, and PUVA. Methotrexate has demonstrated some efficacy at a dose of 20-25mg per week. Dr Shapiro will use 25mg per week for six months and has seen some benefit in patients, especially for the eyebrows.

Lichen Planopilaris

There are different types of lichen planopilaris, i.e., classic lichen planopilaris and frontal fibrosing alopecia. Most dermatologists are only familiar with the classical type and when we look at it under trichoscopy we can see sometimes many hairs coming up out of one hole. We are starting to see more and more of frontal fibrosing alopecia, in fact, Dr Shapiro sees at least two or three new cases per day. It usually occurs in post-menopausal women; however, he has seen it in young women as well, the youngest case being in an eighteen year-old. These patients will start to lose their eyebrows, the hairline will start to recede, and it can also go around the whole scalp.

How do we treat these individuals?

This is all based on experience, as there is no evidence. Dr Shapiro classifies the patients based upon the extent of the condition. If it is less than ten percent hair loss, then he will use clobetasol lotion plus injections with triamcinolone acetonide 10mg/cc for a total of 2ccs. If he sees improvement, he will continue with prn. If there is no improvement, he will treat the patient as if they had more than ten percent hair loss utilizing doxycycline 100mg two times per day or hydroxychloroquine 200mg two times per day, plus or minus ultra-potent topical steroids, plus or minus the injections. Dr Shapiro may also bridge things with prednisone 40mg per day over eight weeks. If there is improvement, he will taper to the lowest effective dose and if there is no improvement there are other options to consider. These options include topical tacrolimus, cyclosprorin A, griseofulvin, mychophenolate mofetil, low-dose isotretinoin, or alefacept.

It has been suggested that these individuals have low PPAR gamma in the scalp. Actos®, a PPAR gamma, did help with symptoms; however, there is an FDA black box warning for bladder carcinoma. This is worrisome for clinicians; however, many of the patients want the treatment. If the patient is aware of the warning and wants the product, Dr Shapiro will give 15-30mg per day.

Take-home Message

When it comes to cicotricial alopecia, they are trichologic emergencies. Early intervention can potentially avert scarring and secondary complications. The diagnosis must be made with a biopsy. Remember that disease-directed medical therapy is only indicated in those with active disease. Adjunctive agents, such as topical minoxidil and hair transplantation, can improve cosmesis.


There is a new medication, N-acetyl-cysteine, that has shown a decrease in obsessive compulsive behavior in patients who take 1200-2400 mgs per day. There are hardly any side effects and it can be found in any healthcare store.

In conclusion, it is important to remember that patient education is crucial. There are websites available such as, and

MauiDerm News Editor: Judy Seraphine





Clinical Pearls-Dermal Filler Complications

Wm. Philip Werschler, MD

It is important to keep in mind that complications can occur when using dermal fillers in clinical practice…It’s important that you:

  • Recognize complications and promptly treat them
  • Not hesitate to see patients in follow-up and refer them if necessary
  • Are truthful with your patients and stay in close contact with them

What about impending necrosis? Remember that impending necrosis as a proposed MOA and patient’s actions may have an impact on the development of impending necrosis…Dr Werschler provides us with some practice tips:

  • Educate staff on concept of impending necrosis
  • Educate and consent patients on risk of necrosis
    • “Scabbing, shedding, discoloration and shallow scarring which may result in prolonged healing and/or the need for reconstructive surgery may occur in rare instances”
  • When patients call and complain of increasing pain, discoloration, headache or other unusual symptoms, instruct staff to have pt. take a NSAID, discontinue cold/ice packs, and come to office for evaluation


Concern of an impending or acute necrosis is a clinical consideration and you should act immediately! Apply a warm compress, nitropaste, confirm NSAID use, and massage as the first step. You should then evaluate the response and consider the use of hyaluronidase and cover with antibiotic, also consider oral corticosteroids. If frank necrosis occurs, utilize HBO2. If necrosis has already occurred, HBO2 speeds tissue repair and healing. Be sure to consult plastic surgery early.




Contact Dermatitis: Clinical Pearls

  • Recently, several new allergens have been added to the T.R.U.E. Test. For topical steroid sensitive individuals the T.R.U.E Test includes: Tixocortol Pivalate (Class A), Budesonide, and Hydrocortisone Butyrate (Class D). Remember that cross reactivity among the various classes of steroids ie A, B, C , D is unpredictable.
  • If anyone is allergic to ANY of the steroid markers on patch testing put them on clocortolone and desoxymetasone (the only two Class C steroids) are the least likely topical steroids to cause sensitivity reactions.
  • Patients allergic to Tixocortol Pivalate have approximately 10% chance of being allergic to systemic prednisone so use oral dexamethasone (Class C) in these patients instead of oral prednisone.

Contact Dermatitis 2014: Diagnosis and Management Strategies

Mathew J. Zirwas, MD


In this presentation, Dr Zirwas, an Associate Professor of Dermatology at Ohio State University and an expert in contact dermatitis, makes understanding contact dermatitis “easy” for the practicing dermatologist…

Dr Zirwas begins the presentation by reviewing some of the new allergens on the T.R.U.E. Test and what we need to know about them…

Steroid Allergies

Tixocortol Pivalate, budesonide, and hydrocortisone butyrate are all markers for allergy to steroid. There is a simplified way to approach the management of this allergy. We know that there are cross-reactor groups A, B, C, D1, D2…in a steroid allergic patient you can either figure out which class they are allergic to, then pick a steroid in a different class (which could still cross-react!) or you can simply use of the two topical steroids that do not cross react with other steroids. These are clocortolone and desoximetasone. These are class C steroids and do not cross-react with anything else.  Also keep in mind that about ten percent of people who react to tixocortol pivalate will have allergy to prednisone if it is given systemically. This is very similar to the way that we think about cephalosporins with penicillin. When someone is allergic to penicillin, we say that there is about a ten to 20 percent chance that they will have a reaction to cephalosporins. This is the same thing, when someone is allergic to tixocortol pivalate, there is about a ten percent chance that they will be allergic to prednisone…they will clear on 40mg, usually stay clear on 20mg and break out in a drug rash around 10mg because the pharmacologic effect of the prednisone is now being outweighed by the allergy to the prednisone.

What if someone is allergic to Diazolidinyl Urea, Imidazolidinyl Urea, 2-Bromo-2-nitropropane-1, 3-diol?

For these patients, treat them as if they are formaldehyde allergic. They may be allergic to only one or two formaldehyde-releasing preservatives, but 90 percent plus are formaldehyde allergic and need to avoid all the formaldehyde related substances. It is a little bit more of a conservative approach, but it’s the approach that experts in contact dermatitis use.

What if a patient comes in stating that she is allergic to titanium dioxide?

Remember that allergy to titanium dioxide is extremely uncommon. This patient may be allergic to gold sodium thiosulfate. How is gold related to titanium? Gold is related to titanium dioxide because gold, itself, is very inert; however, it interacts with titanium dioxide, which is in most make-ups and sunscreens. The problem is that it interacts with the gold jewelry that women wear; therefore, they may break out in a rash where they apply their make-up/sunscreen. These patients need to either stop wearing make-up and sunscreen OR replace their gold jewelry with platinum, which is the best replacement for gold. Patch test reactions to gold can persist for three to six months. If they persist, Dr Zirwas will inject 0.1-0.5ml of TAC-5.

What about a patient who comes in with a facial rash every spring?

A patch test may determine that this patient is allergic to parthenolide. Parthenolide is a marker for an allergy to the Compositae family of plants. There are around 20,000 plants in this group but as dermatologists we only need to remember a few key points about this group. The first of which is to avoid Aquaphor. Aquaphor has bisabolo in it, an extract of German Chamomile, which is in this group. In general, Dr Zirwas tells parthenolide allergic patients to avoid anything that has to do with a botanical.  This is a conservative approach; however, it is much more effective than determining to which of the 20,000 plants a patient may be allergic.  Some patients can get airborne contact dermatitis from pollens that have SQLs on the surface, especially ragweed and goldenrod. These can be difficult patients; they either need to move somewhere with less pollen, or they should be immunosuppressed during the months of the year when they tend to get this allergy.

Allergies to Dyes

There are thousands of different dyes that are used to dye clothing. Disperse Blue 106/124, while not great for ruling out textile dye allergy, is the best screening agent we’ve got.  Remember that you cannot tell what dye was used based upon the color of the clothing. If a patient is positive, then synthetic textiles of all colors become suspect. These allergic reactions tend to be acute and intermittent. Usually, specific items of clothing can be identified, such as exercise clothing and liners in dress clothing. Normally, once you tell the patient what to look for, they can tell which items of clothing are causing the reaction.

Other T.R.U.E. Test Allergens

  • Quinoline Mix
    • Rarely relevant- Bag Balm, some others
  • Mercaptobenzothiazole
    • No different than other rubber accelerators
  • Bacitracin
    • Need to avoid polysporin, etc.


T.R.U.E. Test Conclusions

The T.R.U.E. Test is better than it used to be; however, it is still not that good for certain things. It is good for identifying allergies to metal, rubber gloves, and topical antibacterials. It is NOT good for personal care products, make-up, topical steroids, and other interesting things such as acrylic nails, prosthetic joints, sports equipment, etc.

The T.R.U.E. Test is best for ruling IN a diagnosis of rubber glove allergy, neosporin/polysporin allergy, and metal allergy. Its WORSE uses are in ruling out contact dermatitis when you’re unsure of the etiology.

What are the chances that a patient will get better with the T.R.U.E. test?

Considering patients who aren’t allergic to metal, rubber, or polysporin, it’s actually about one percent. How does Dr Zirwas get this number? Well, when you look at a patient and think it might be contact dermatitis, but aren’t sure to what, the chances are that it is contact dermatitis in about 20 percent. The probability of an accurate diagnosis with the T.R.U.E. test is about 20 percent. The probability that a patient will remember what they are allergic to is about 50 percent, at best.  The probability that the patient will avoid the allergen, if they remember it, is 50 percent, at best. Therefore, 20% x 30% x 50% x 50% = 1% (at best).

What else can we do?

The American Contact Dermatitis Society publishes a list of allergens and a screening panel, which is an excellent resource for people who want to implement comprehensive patch testing.  But what do you need at a minimum? You need to buy ten tubes of allergen and one box of Finn® chambers. This will cost about $400.00

Supplement the T.R.U.E. Test with following 10 allergens:

  • Methylisothiazolinone 2000 ppm
  • Formaldehyde 2%
  • Propylene Glycol 100%
  • Fragrance Mix II
  • Cocamidopropyl Betaine
  • Amidoamine
  • Dimethylaminopropylamine
  • Hydroxyethyl Methacrylate
  • Ethyl Ethacrylate
  • Propolis

Additionally, The American Contact Dermatitis Society has a database, CAMP. This is very user-friendly, i.e., you check the boxes with regards to what the patient is allergic and it, in return, provides you with a list of safe products for that specific patient. This way, your patients do not have to read labels and figure out what to avoid, you can simply provide them with a list of products that they CAN use. is another resource containing a series of free-access videos that review all of the remotely common allergens. There are also handouts that go along with the videos and they are extremely useful.

Methylisothiazolinone 2000 is an enormous epidemic. This is probably due to a combination of reasons; firstly, there is increased exposure because of the move away from parabens and formaldehyde-based preservatives. Second, until recently, we have been patch testing with too low a concentration and as a result, for the last 10-15 years, we have probably been missing a lot of the people who are allergic to this. Remember the 3 Fs—Faces, Fannies and Fingers. Methylisothiazolinone is often found in shampoos, conditioners, facial soaps, moist toilet paper, hand soaps, and baby wipes.

Formaldehyde is still a very common allergen. One percent formaldehyde, which is the standard allergen, misses a lot of cases; therefore, we have gone to testing formaldehyde two percent.  You get a few more irritant reactions, but pick up a lot more cases of true allergy.

Propylene glycol is now tested at 100 percent. You do not get irritant reactions, but you do pick up a lot more reactions than when we used to test with 30 percent. Propylene glycol is in most topical steroids and NEEDS to be ruled out as a cause of chronic dermatitis.

Fragrance Mix 2 is no different in terms of clinical manifestations compared to the original Fragrance Mix, but these are newer fragrances that are more relevant and pertinent. If you are only testing with FM1 and Balsam of Peru, then you are probably missing 30 percent of fragrance allergy patients.

Cocamidopropyl betaine, amidoamine, and dimethylaminopropylamine are three different ways to test for allergy to modern lathering/foaming agents. Lathering agents are a very common cause of facial dermatitis from shampoos, facial cleansers, and conditioners. Keep in mind that while conditioners do not lather, there is a related ingredient called stearamidopropyl dimethylamine that is chemically related.

Hydroxyethyl methacrylate and ethyl acrylate are the best markers for acrylate allergy, a common cause of allergy from nail cosmetics. This is a much more common problem than nail polish allergy and these patients MUST avoid all types of artificial nails (acrylic, gel, solar, wraps, tips, etc..) This allergy also indicates a need to avoid bone cement in prosthetic joints.  If a patient is allergic to acrylates, this is a much bigger problem than if they were allergic to nickel and they receive a metal implant.  There is a lot of controversy around whether or not a metal implant will be problematic for patients who are allergic to nickel, but general agreement that acrylate allergic patients will have a problem if bone cement is used when putting in a prosthetic joint.

Propolis is the last of the ten allergens that Dr Zirwas would use in addition to the T.R.U.E. Test. Propolis is related to beeswax and is found in a lot more products than you would think, it is especially a problem in some lip products.

If a patient presents with widespread dermatitis, but not on the face, they may be allergic to potassium peroxymonosulfate, the active ingredient in shock treatment for hot tubs (and pools).  Dr Zirwas sees this mostly in male patients. Why? Because men are the ones who are taking care of the hot tub/pool, adding the treatment and are subsequently exposed to high concentrations while scooping it out of the container, leading to sensitization.  Then, when they get in, they break out in a widespread rash.  If a patient has widespread dermatitis, he/she should stay out of their hot tub. If they get better, they should change the shock treatment to H202 or hypercholorination.

If a patient has papules on extensor elbows, you should consider dietary nickel as a possible cause – this is a much more common cause of itching papules on the elbows than is dermatitis herpetiformis.  He/she should consider a low nickel diet consisting of oatmeal, legumes, canned goods, dark chocolate, stainless steel pots/pans, and should only drink bottled or distilled water. Patients should also take vitamin C with every meal.


Contact dermatitis can be a challenge for the practicing dermatologist. Keep in mind that the T.R.U.E. Test is best for ruling IN a diagnosis of rubber glove allergy, neosporin/polysporin allergy, and metal allergy. Its WORSE uses are in ruling out contact dermatitis when you’re unsure of the etiology.  Remember to supplement the T.R.U.E. Test with the ten allergens previously discussed.


MauiDerm News Editor- Judy Seraphine


Fillers 2014: New Fillers and New Data

Wm. Philip Werschler, MD

In this presentation at MauiDerm 2014, Dr Werschler, a pioneer in the area of toxins and fillers, provided an overview of the fillers currently available on the market along with newer fillers and new data so that we can utilize this information in clinical practice.

A Brief History of Their Time

We started off with collagen, if you wanted a filler, that’s what you got. This is no longer available. At that point in time, we were really focusing on lines and wrinkles. Collagen became products such as Zyplast and Zyderm and was mostly used on lips, crows feet lines, nasolabial folds, and vermillion borders. Then, for many, many years, we had a lull. So, you either did collagen or you didn’t do injectable fillers.Then starting in   2003, the filler market exploded, as you can see from the chart below.

Screen Shot 2014-01-14 at 9.47.08 AM


In December, 2003, the US FDA approved Restylane (Hyaluronic Acid), which revolutionized the dermal filler market . With a duration of six plus months, no pre-treatment skin testing, ease of use, room temperature storage and modest cost, there was now a viable product for the emerging, if nascent, dermal filler market.

Radiesse is a novel “next-generation” filler that was approved in 2006 by the FDA for the correction of wrinkles and folds (such as Nasolabial Folds), and for the correction of HIV-associated lipoatrophy. Radiesse is termed a “stimulatory” or “collagen-stimulator” product.  This differs from the previous generation “replacement” space occupying materials collagen and hyaluronic acid.  With the addition of collagen stimulation, the duration of effect of Radiesse was extended to 9-18 months.

On the same day that Radiesse was approved, the FDA also approved the first and only “permanent” dermal filler, Artefill (collagen + PMMA).  Artefill consists of bovine collagen in combination with polymethmethacrylate spheres.   As these spheres are non-biodegradable, they represent a permanent placement into the tissue.  Well tolerated with an excellent safety profile, Artefill does require pre-treatment skin testing because of the bovine collagen present. Special handling includes refrigeration, and collagen stimulation gradually anchors the PMMA spheres into place typically after 2-3 treatments.

In 2007/2008 Hyaluronic Acid plus lidocaine was FDA approved for the hyaluronic acids, Juvederm, Restylane and Perlane. Similarly, the FDA approved the mixing of lidocaine and Radiesse by the injector at the time of use.  These approvals resulted in greater patient comfort during injection and further expanded the dermal filler marketplace. Stabilized Porcine Collagen came onto the market briefly during this time, however due to problems with patient tolerance and complications, the manufacturer withdrew the product and it is no longer available.

In 2009, the FDA approved Sculptra, poly L lactic acid, for aesthetic use (it received FDA approval in 2004 for HIV associated facial lipoatrophy).  A pure collagen stimulator, Sculptra, is technically not actually a dermal filler, however; it is best thought of in this category.  Sculptra is routinely mixed with lidocaine and sterile water for injection, requires 3-5 injections sessions to gradually grow new collagen leading to the clinical effect developing over a period of three to six months.  Duration is a 2+ years effect based on extensive clinical trials and experience.

More recently, an advanced technology hyaluronic acid, Belotero, and  an autologous cultured dermal fibroblast  (LAVIV)  were approved. Laviv, like Sculptra, is technically not a dermal filler but rather a tissue stimulator that up-regulates native collagen production.  This process includes harvesting tissue from the patient (post-auricular) and sending it to a processing laboratory that then amplifies the cell count and returns a viable culture for re-injection. The first FDA approved tissue cell culture therapy for aesthetics, Laviv, presents a multitude of intriguing possibilities in the future.

Most recently (2013), we have hyaluronic acid with Vycross technology, known as Voluma.

In order to use fillers, it is important to understand their mechanism of action. There are two primary components of MOA:

  • Volume Replacement
  • Collagen Stimulation-either as part of its MOA or its primary MOA

If you use the above approach, collagen and hyaluronic acids have an immediate correction and they do not really have, as a primary mechanism of action, any neocollagenesis effect; therefore, collagen and hyaluronic acids are replacement fillers. PLLA (Sculptra) and LAVIV are bio-stimulatory. And notably, CaHA and PMMA are blends of both MOAs.

Screen Shot 2014-03-31 at 8.17.30 AM


How do fillers exert their characteristics?

Fillers are commonly compared by viscosity ,elasticity and cohesivity, the three physical properties that dictate the ability of a filler to provide volume plus lift and the ability to resist becoming separated in tissue. All three of these measurements are made in-vitro, and are surrogate measures for in-vivo activity. Viscosity is the measurement of a material’s ability to resist a force that is applied to it. It relates to the movement of the material in response to force. So, highly viscous materials require more force to move or spread compared to lower viscous materials. A filler with a high viscosity “stays where you put it”, providing a “what you see is what you get” results. Fillers with lower viscosity will have the propensity to be easily spread and splay into surrounding tissues.

Screen Shot 2014-03-31 at 8.17.45 AM


You’ll see on the graph above that the products with the greater viscosity are Radiesse and Restylane SubQ (not available in the US). Does this mean that they are better products? Not necessarily, it depends on the tissue characteristics for which you are looking. It means that these products have more of an ability to push back against a force that is applied to them.

Elasticity, measured as G’, is the material’s ability to push back against a force that is applied to it. Fillers with a high G’ will resist the forces placed on it, such as gravity, skin laxity, etc. and will provide greater lift to the overlying tissues. Fillers with a low G’ will not have the capacity to lift well, and; therefore, require larger volumes of material to compensate.

Screen Shot 2014-03-31 at 8.17.59 AM


What does this mean clinically? Well, in part it means that some activity of a filler can be predicted by laboratory measurements. It also means that only personal experience can determine which filler you use for any particular indication and patient experience and satisfaction will determine the final choice of product.

These are important concepts to think about. Some products provide soft lifting and some products provide a firm lifting.

Volume Replacement

Hyaluronic Acids (HAs)

Volume replacement is all about HAs today in the marketplace. It is when you inject a product that occupies a space and holds that space until that product is either removed or, in the case of HAs, is degraded through natural enzyme processing.

HAs have a very simple chemical structure and is identical in all species and tissues; thus it is non-immunogenic. It is found in all vertebrates and synthesized by some bacteria. The identical structure of HA from all sources makes it an ideal substance for use as a biomaterial in health and medicine.  HAs are highly hydrophilic; therefore, they absorb water, i.e., their principal method of giving a volumizing effect. They are also rapidly metabolized in vivo.

HA was first discovered in 1934 by Meyer and Palmer and was first used therapeutically in 1970. During the 1980s, Biomatrix, Inc. developed second-generation HA derivitives (hylans) through cross-linking (stabilization), and in 1986 the term “hyaluronan” was coined. The increased stabilization increases the ability of the product to do the work that you want it to do. By 1996, we had the first generation of resorbable gels based on hyaluronic acid of animal origin. In 1998, we had the second generation of resorbable gels based on hyaluronic acid of non-animal origin—these were biphasic products. In 2000, the third generation of resorbable gels came about, based on hyaluronic acid of non-animal origin—monodensified, mono-phasic products. And, in 2005, we saw more technological advances with Cohesive Polydensified Matrix technology, allowing for different tissue characteristics.

HAs can be used virtually everywhere for anything and everything and they are the most versatile of all of the filler products. These fillers may be ideal for novice patients because they have an  “eraser” (hyaluronidase) that can be injected to make the product dissolve, if so desired for either aesthetic effect or for treatment of complications including necrosis. . This is a unique feature of this category. Remember that while some HAs seems to work better in certain areas, this is based on personal preference.

What’s New?

  • Voluma XC
  • Belotero (sort of)
  • Expressions (kind of)
  • Corporate acquisitions and news

Vycross Technology

Juvederm Voluma XC is FDA approved HA to correct age-related volume loss in the mid-face. We know that volume loss creates the aging changes. The VYCROSS technology formulation produces highly cross-linked gel, increasing lift, capacity, and duration. The duration of this product is up to two years. Duration claims  are always a slippery slope, so be sure to caution your patients.

The pivotal clinical study was a multi-center, single blind, no-treatment control study of 282 subjects (235 in the treatment group/47 control “no treatment”) in fifteen North American sites. The subjects received 20 mg/ml HA volumizing filler for cheek augmentation to correct mid-face volume deficit. There was one treatment plus one optional “touch-up” one month later.

Eligible subjects must have scored an overall Mid-Face Volume Deficit score of greater than three on a six-point scale.

  • 3 = moderate concavity of mid face, tear troughs, mild nasojugal and pre-jowl, mild prominence of bony landmarks and musculature
  • 4 = significant concavity of mid-face, tear troughs, moderate nasojugal and pre-jowl, moderate prominence of bony landmarks and musculature
  • 5 = severe concavity of mid face, tear troughs, severe nasojugal and pre-jowl, moderate prominence of bony landmarks and musculature

The study endpoint looked at the Mid-Face Volume Deficit scale at six months with the primary endpoint being greater than 70 percent responder rate versus control. The primary endpoint was met with an 85.6 percent treatment group response rate.

Subject Rated Duration

6 months = 95.1%

12 months = 80.4%

18 months = 67%

24 months = 53.7%

Physician Rated Duration

6 months = 76.8%

12 months = 64.3%

18 months = 57.9%

24 months = 46%The range of volume used in the study was rather dramatic as it went from 1.2mL to 13.9mL. The median for all three subregion treatment areas (mid-face) was 6.6mL.

VYCROSS technology has opened up the mid-face volumization category for us, as practitioners.

CPM Technology

Belotero is a “cohesive polydensified matrix” hyaluronic acid.  CPM technology allows for variable degrees of product/tissue integration. With less homogenous bulk, there is less monochromatic refraction of ambient light. The net clinical result is that the product may be injected more superficially than other HAs without risk of the Rayleigh/Tyndall effect tinting the skin blue.


Expressions is a hyaluronic acid filler that is FDA approved for nasal splinting; however, it is not FDA approved for aesthetic use, yet it is heavily marketed to the aesthetic community. Expressions is an HA product that is made with Bacillus Subtilis Fermentation and it comes in a 1.5mL syringe.

New Approaches to Fillers


Poly-L-Lactic Acid

Through a variety of mechanisms of action, they stimulate fibroblasts to make collagen, making Sculptra more of a tissue stimulator as opposed to a filler, per se.

It is the only approved pure collagen stimulator currently available in the US; therefore, it is considered “stimulatory” and “biodegradable” in classification. PLLA is indicated for the correction of nasolabial folds. Of note, Dermik aesthetics, a division of sanofi-aventis, recently sold the product to Valeant Pharmaceuticals Intl. based in Canada. It takes time and a number of treatments; however, the duration is about two to three years. It is important to remember that it is difficult to establish exact duration of the product because of one’s natural course of aging.

What is the composition of PLLA?

  • Poly-L-lactic acid
  • Sodium  carboxymethylcellulose (CMC)
  • Non-pyrogenic mannitol
  • Sterile water (added) for injection (USP)
  • Lidocaine (optional—most dermatologists and plastic surgeons add lidocaine for patient comfort)

Sculptra™ is composed of microparticles of PLLA, a biocompatible, biodegradable, synthetic polymer from the alpha-hydroxy-acid family.  It is derived from natural components, it is a crystalline, amorphous mixture with microparticles averaging 40 to 63 μm in size. The slow resorption of PLLA after implantation is due to the high molecular weight (140,000 Daltons) of the polymer and the irregular crystalline shape of the microparticles.

Lactic acid can be converted through polymerization to a variety of polymers, including poly-L-lactic acid. Many of these polymers, including polylactic acid, have been used for many years in medical devices and sutures, including absorbable sealants, flow restrictors, fixation systems, suture anchors/absorbable sutures, fixation screws, and tissue regeneration.

Investigator evaluations throughout the study confirmed that improvements in facial appearance with Sculptra®Aesthetic were achieved in WAS. As this graph shows, improvements from baseline at 25 months proved to be consistent, progressive, and statistically significant at each time point (P<0.001): 100% of patients improved at week 3; 88.7% at month 13; and 86.3% at month 25.

Screen Shot 2014-03-31 at 8.18.19 AM

Where is it used?

Poly-L-lactic acid treatment primarily to add volume, and as such is used to thicken dermis and to stimulate collagen growth in the pre-periosteal plane.  Placement may include the temporal hollows, across the zygomata, in the mid face, nasolabial folds, labiomental sulcus, prejowl sulcus, mandibular sweep and angle and for genioplasty.  Sculptra is not recommended for use in areas of concentric movement such as the lips and eyelids.  In terms of adding volume, this is a great way to go. As you become skilled with PLLA, there are a lot of great things that you can do with it over time.

Personalized Dermal Technology

Azficel-T (LaViv) is an interesting, innovative technology to isolate, purify, and regenerate a patient’s own fibroblast cells for re-injection.

Fibroblast cells produce collagen and play key role in the continued health of skin. Collagen provides firmness and structure to the skin and is essential in supporting the dermis. As skin ages, fibroblast cells decrease and the collagen matrix that provide the skin its structure breaks down.

This is a way to restore the equilibrium.  LaViv is the first autologous cell therapy for use in aesthetics filed with the FDA. There is strict release testing on each clinical lot to ensure performance and safety including:

  • Collagen content testing results must achieve specification for each prepped injection, indicating cells are biologically active and produce collagen
  • Cell suspension must consist of at least 98% fibroblasts prior to release
  • Cells in suspension must achieve a viability level of at least 85%
Treatment Process

A small cell sample is removed from behind the ear from a small skin punch biopsy with the use of a local anesthetic. A proprietary manufacturing process multiplies the fibroblasts from the sample into tens of millions of new cells in approximately three months. The fibroblasts are tested by quality control and released by quality assurance prior to the shipment. The cells are then frozen for use in potentially multiple treatment sessions. The recommended regimen is three treatment sessions at three to six week intervals. In clinical trials, Azficel-T and placebo was seen by the time of the third treatment. Dr Werschler feels that if you have a patient who doesn’t want a “foreign” substance used for aesthetic purposes, this is a nice alternative to be able to offer as it’s personalized dermal cell technology. Of note, the side effects are minimal, mostly pruritis.

Screen Shot 2014-03-31 at 8.18.42 AM

Volume Replacement + NeoCollagenesis

Calcium Hydroxylapatite (CaHa)-Radiesse

CaHA has a biphasic MOA, it is 30 percent calcium particles and 70 percent CMC gel. CaHa is best used for regional facial contouring. Dr Werschler uses this product for structural augmentation, i.e., helping to define the face. Its mechanism of action is to serve as a filler material initially (particles + gel) then provide long-term benefit through natural collagen integration in and around the particles. The result is a long lasting, but not permanent correction augmentation that feels like the patient’s own tissue. Remember with Sculptra, the volume effect comes from neocollagenesis; however, with Radiesse, because it is a biphasic product, you get an immediate corrective effect which then stimulates neocollagenesis at a rate which prolongs the effect clinically that you see; therefore lasting longer.

The advantages of Radiesse include immediate site-specific correction in one to two sessions and strong structural tissue support with no Rayleigh/Tyndall effect. CaHa is malleable up to two weeks and has a long duration of nine to 18 months. No pretreatment testing is required, it is also cost-effective and does not migrate or obscure radiographic studies and it doesn’t ossify in the skin. Radiesse received approval in the United Sates in 2006 for both HIV and aesthetic use and is the only approved biodegradable dual collagen stimulator and replacement filler currently available in the US. When utilizing Radiesse, no skin or allergy testing is needed and there is no special handling. The product is available in 0.3, 0.8 and 1.5 mL and recently approved 3.0 mL syringes through Merz Aesthetics.

Where is it used?

CaHA is used most everywhere; however, it is not recommended to be used in the lips or around the eyes.

Screen Shot 2014-03-31 at 8.18.56 AM

PMMA Dermal Filler-ArteFill

ArteFill was approved in the United Sates in 2006 and is the only approved PMMA-enhanced dermal filler currently available in the US. It is indicated for the correction of nasolabial folds. Suneva Medical acquired (ARTES) Artefill in 2009 and is currently manufacturing, selling, and distributing Artefill in the US. Of note, it is currently awaiting FDA approval for acne scars.

ArteFill is a combination of purified bovine collagen plus polymethyl-methacrylate beads. Essentially, you drop the beads into the tissue that are then carried by the bovine collagen that is then rapidly reabsorbed. You see a neocollagenesis effect from the fibroblasts around the PMMA particles that are locked into place so that they do not migrate providing a long-standing correction. You can see from the graph below that the five-year follow-up study demonstrates long-lasting effects.

Screen Shot 2014-03-31 at 8.19.09 AM


Injectables are: Facial Shaping Agents

  • They can enhance natural features
  • They can rejuvenate fading youth
  • They can restore aged, facial features
  • They can even improve natural beauty
  • Each product has features that result in certain benefits in clinical use
  • They are not all alike!

What’s new?

  • Not that much…but quite a bit
  • CPM technology is “back” on market
  • Valeant owns Medicis, Dermik
  • FDA approval for Allergan’s Vycross technology mid-face volumizer
  • Expressions is in the neighborhood
  • Merz has acquired Neocutis
  • Allergan has acquired SkinMedica
  • Valeant (Medicis/Dermik) has Obaji
  • Merz acquired Anteis (Beletero family-Soft, Basic, Intense)

Additionally, Allergan has clinical trials underway in the United States for Volbella and Volift. A new player, Alphaeon, has products at different states of pre-approval; they have licensed Teoxane (filler and skincare line), they have also licensed a neurotoxin which is not yet on the market and the company plans to expand on lifestyle medicine, focused on wellness, beauty and performance.

Clinical Pearls

  • Use filling agents appropriate to the requirements of the job
    • Lifting tissue requires robust strength, longevity, durability, and safety
    • For surface “crinkles” use “thin” or “dilute” products
  • Not all products are created equal – understand the differences!
    • Some products create “soft” volume, others “firm” volume
  • Some areas are more difficult to correct than others  (e.g. lips and tear troughs)
    • Create facial filling improvement by starting with low-risk/high-satisfaction areas—utilize a STEP approach
  • Evaluate and approach filling from a multi-step progression:
    • Integrate filling with development of structure and support, progress to volume replacement and refine with contour
  • Product duration claims are a slippery slope—be careful with those and be conservative with your ranges


MauiDerm News Editor- Judy Seraphine