Hot Papers in Acne

Written by: Judy Seraphine

At MauiDerm 2014, Dr Webster lead off the discussion by reviewing 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, this is based upon youth, severity, diet, and hormones. We have learned 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. A paper published in the International Journal of Dermatology in 2012 demonstrated that isotretinoin 290 mg/kg had a 12 percent relapse rate over three years; of note, adverse events were not any worse. Another retrospective paper, published in JAMA Derm in 2013, showed that isotretinoin greater than 220 mg/kg had a relapse of 27 percent versus 48 percent in doses less than 220 mg/kg—so the really high dose had a lower rate, but it was still somewhat high. Those who received the higher dose did have increased dermatitis.  Another finding from the study was that those on the higher dose of isotretinoin were aching a lot longer even when the isotretinoin was over; this is something that we don’t see with the standard dosing. 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.

A 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; in fact, there is a 50 percent decrease of isotretinoin if taken on an empty stomach. Dr Webster feels that the most common cause of isotretinoin resistance and relapse 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. Dr Webster comments that whether or not you use this new drug or regular isotretinoin, it really should be taken with some fat in the stomach.

Figure 1 depicts the absorption rates with Accutane 40mg “fed” versus “fasted” and you can see that there is a significant difference.

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With the new product, isotretinoin-lidose, you can see that the absorption rate in Accutante (fasted) is exactly the same; however, the newer form of isotretinoin (fasted) is much higher. This drug may be helpful for compliance-challenged patients. (See Figure 2)

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What about P. acnes?

Recently, there have been a couple of papers that have been published suggesting that there may be a particularly hot strain of P. acnes that is causing acne. Years ago, one of Dr Webster’s first papers was looking at all of the strains of P. acnes with a bacteriophage typing system and they found that there were many strains of P. acnes that were reproducibly different, but there was no difference in where they showed up, i.e., the same spread of strains whether it was inflammatory or non-inflammatory acne or whether it was isolated from CNS surgery or from hip infections.

A recent paper, published in the Journal of Investigative Dermatology, 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; therefore, some strains are associated with inflammatory acne. A second paper, published in the British Journal of Dermatology, found that this association; however, is a trend and not an absolute, i.e., there were patients with bad acne who had the “non-inflammatory” strain and there were patients with no acne who had the “inflammatory” strain. Typically patients with inflammatory acne had a mixture of the two with the “bad strain” predominating.

How do you explain this and does it make sense? Does it mean that people with bad acne need to have their P. acnes replaced with a non-verulent strain so that they don’t get pimples? Or is this an ecological issue? The skin microbiome is a microecology in the same way that a swamp has its own ecology. Different selective pressures do different things to the microenvironment. For example, if you sample the forehead, it is very rich in P. acnes and malassezia. If you sample the forearm, there are usually no sebaceous glands and there is no food for P. acnes so you don’t get a lot of growth from P. acnes. This tells us that big variations in environments lead to big variations in strains.

Dr Webster suspects that this difference in P. acnes distribution between acne and non-acne is not necessarily “bad strain” versus “good strain”, it’s that inflammation is a selective pressure just like the presence or absence of food/water in an ecosystem; this adds oxidative stress on the bacteria. Remember that P. acnes defends itself against oxidation pretty well even though it is an anaerobe. Dr Webster feels that the enrichment of type 1a strains in patients with inflammatory acne is merely showing that inflammation selects through strains that can survive better in a more oxidized environment.  As dermatologists, we really need to look at how strain 1a is different from strain 1b—does it defend itself better against oxidation?

 

 

 

 

 

Introduction to Lasers and Light (And a Touch of RF and Microwave)

E.V. Ross, MD

Dr Ross, a leader in the field of laser and light therapy, provided the audience with an in-depth overview on lasers and light. Dr Ross begins by reminding us that we tend to look for the “easy” way out to make our patients look their best with the least downtime. In order to be efficient and effective for his patients, Dr Ross likes to have many lasers in one room; therefore, providing the best possible technology.

It is important that we really understand laser physics. You need to know some math, but it doesn’t have to be difficult math. You can take very complex mathematical relationships and break them down into very simple algebraic relationships. By doing so, you can actually apply your lasers and other technologies quite confidently. It’s imperative to understand how they work because if you don’t, you can get into trouble very fast. Remember to look, listen and feel….listen to the reaction, look at the laser, look at the patient at every pulse to be sure the endpoint is what you want to see because ultimately, the endpoint is more important than the physics.

When we talk about lasers, we need to know some basic definitions. One of the most important terms is fluence; fluence is simply the light dose, i.e., the amount of energy that we are investing per surface area for a particular application.  We used to speak a lot about power, e.g. 7 watts power or 12 watts power. Currently, we don’t talk much about power because most of our lasers today are pulsed lasers. What really matters are wavelength, fluence and pulse duration. Pulse Width is  very important, i.e., the time over which energy is delivered. Spot size, which contributes to the intensity inside the skin, is mainly important for visible light lasers and infrared lasers because a larger spot will penetrate better.

LASER, Light Amplification by the Stimulated Emission of Radiation, is a concept that Einstein predicted back in the 1920s, but it was not realized until May of 1960.

Why is laser different than a lot of other light sources? We can use a lot of non-laser light sources in dermatology and certainly achieve nice results. Intense pulsed light is a great example. There are some features of lasers that make them helpful for dermatology and helpful for certain applications, but not always necessary for every application.  (See http://www.colorado.edu/physics/2000/lasers/index.html)

Why is it important to differentiate laser light from non-laser light? Dr Ross explains that it is because of engineering more than anything else. Most of our targets that we treat in dermatology have multiple wavelengths as far as their absorption. Lasers are a convenient way to deliver light, i.e., deliver photons to the target. This is why lasers are so popular. You can put lasers into a fiber, you can have monochromatic light, and you can deliver very high power. It’s the only way to really deliver very short pulses in nanoseconds and picoseconds for certain applications.

Why do we need to know how/why lasers, etc. work?

Dr Ross states that one important reason is that when your laser breaks down, which can happen, you want to understand why it isn’t working. If you have a good understanding of how your laser works, you may be able to correctly diagnose that. If you see that your laser isn’t working right, often times there’s an error code. It’s important that you write down the code and report that to the technician. Sometimes it’s as simple as restarting the system.

You should be able to troubleshoot laser problems in a logical way…Device malfunction is one problem, an example is a temperature sensor malfunction. However, a bigger problem could be your lack of familiarity with the device; most laser problems are caused by the operator because they’re not familiar with how the device works—sometimes they are rented and sometimes they are only used once per week. Other factors that contribute to laser problems include poor patient selection, operational errors, poor post-treatment care, and simply bad luck.

Dr Ross reminds us that we have to think. Most of the time when we get into trouble with lasers it’s because we weren’t thinking—invest all of your brain power into that particular case while you’re performing the procedure and that means paying particular attention to endpoints.

Four years ago right before the Christmas holiday, Dr Ross had a typical case of a woman who came in for treatment of telangiectasias with a pulsed-dye laser. He used the pulsed-dye laser, 10mm spot, 7 J/cm2, and a 10-millisecond pulse and everything was looking fine. The patient developed some mild purpura and she was incredibly upset. So what happened? She didn’t have any blisters and everything else was fine. Dr Ross went back and looked at the beam profile and found that it was off by about 2mm (8mm instead of 10mm).  What had then happened was that the fiber was damaged so they were delivering the right energy but in a smaller spot; therefore, causing the fluence to become higher and the purpura threshold had become breached. The technicians then fixed the beam profile and there was no more purpura. Dr Ross reminds us that sometimes we may have to do some detective work to figure out what’s going on.

Broken mirrors can also compromise your laser experience.  Particularly with the CO2 laser, if your beam profile doesn’t look good it may be due to a broken mirror.

When your calibration doesn’t pass,  the most common reason is because of a bad lamp.

What we’re seeing now is a progressive change in laser technology. Lasers are becoming quieter, cooler, smaller, better and more reliable. We now have small, portable lasers (see figure 1) and maybe, in the near future, we’ll see small lasers that can treat everything from tattoos to resurfacing.

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Remember that with most of the lasers that we’re using today, the light piece is “back in the box” and is delivered through some sort of delivery system; however, in the case of some of the mini diode lasers, the light is in the hand piece. (See Figure 2)

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Over the next few years, we are also going to see more and more LEDs. We are going to begin to see more safety features that will be incorporated into the software with touchscreens. For example, you may have a patient who came in for treatment of a wart so the technician turns the dynamic cooling device off. Then, your next patient is coming for treatment of a port wine stain and the technician forgets to turn the DCD back on and the patient gets a blister from the very first pulse. What if there was a tool that provided a warning signal indicating that the DCD was off? Actually that feature is already built into one popular pulsed dye laser.

What about photon recycling? This is a way to capture some of the photons that were wasted. Whenever we use a laser much of the energy is reflected back off the skin surface. By recycling the energy we have a second chance to use those photons. This preserves energy and puts less stress on the system. We will also see more and more scanning technologies as they are becoming increasingly robust. In the future, we will probably see scanners that will find the target and treat it.

Another concept that Dr Ross discusses is the TRASER (Total Reflection Amplication of Spontaneous Emission of Radiation). The traser is not a laser, nor an IPL. This is one device with many wavelengths that is tunable, has high peak power and variable pulse duration. This device is actually less expensive than a laser and you can change the dye very quickly. The traser uses total internal reflection. We know that if we take light beyond a critical angle, the light will come back towards the same direction.

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Overall, with lasers in dermatology, you only have to know the chromophore spectra of three targets: blood, melanin, and water. If you know the relative absorption for specific wavelengths for these three targets, you will be a fairly well-armed laser surgeon.

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When you model a laser-tissue interaction, you want to look (in your mind) at the way that the light propagates through the skin to the target. You have to get the light to the target. Then, depending on the pulse duration and the wavelength you’re going to have a certain amount of temperature increase leading to a response from that target due to the temperature and time combination.

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What about skin optics? It’s important that you determine the penetration, the absorption and scattering, and the internal dosimetry.

Laser Tissue Interaction Types

There are different types of interactions. The main type that we use in dermatology is thermal, in that we are basically converting light into heat. Other types of interactions include mechanical, chemical, and plasma. Dr Ross feels that one of best ways to learn about laser tissue interaction is through laser hair reduction. The laser comes down, and a certain amount of the light is going to reach the hair bulb, based on the optical properties of the skin. Typically for 1064nm, about 30 percent of the light is going to get about 3mm down which is the typical depth for a hair follicle. Depending on the pulse width, the wavelength, and the fluence, you will have a certain temperature elevation of that hair bulb and some of that heat is going to diffuse to the surrounding skin. So long as the temperature and the time combination is relatively small, you won’t have too much collateral damage—you will only damage the hair follicle.

Selective photothermolysis was a formal termed coined by Dr Rox Anderson 32 years ago. What it says is that if you have the right wavelength, the right pulse duration,  the right target, and sufficient energy,  you will achieve extreme localized heating. This really revolutionized the way in which we treat vascular and pigmented lesions.

As a dermatologist, you should always remember the graph below, where the wavelength is on the X axis, and you have the relative chromophore absorption in the Y axis. If so, you will be a well-armed laser surgeon. Just like a neurologist looking at an EEG and a cardiologist looking at an EKG, this should be second nature to you.

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How can we exploit laser physics? An example of this is a scar. When we have a scar, there is usually some feature that makes it different from the surrounding skin. You can take a laser and exploit that, whether its redness or pigment in the scar.

This is the temperature equation that basically tells us how hot targets get…the temperature elevation of any target is proportional to the relative absorption of that target for that wavelength of light times the energy div over by a constant. This is very simple concept as its basically energy balanced. Where is the equation??

As you go to longer pulses, the selectivity of the heating becomes poorer but the violent nature of it becomes less.

Fat

Dr Ross states that we are still woefully poor at targeting fat, whether it’s radiofrequency or laser. There are a couple of wavelengths that can be useful for exploiting fat; 1210nm and 1720nm. Those are the wavelengths where fat absorption is in excess of water absorption. However, the ratio of absorption from fat to water is only 1.2 or 1.1 to 1. When we treat a vascular lesion, our absorption rate for the blood is more like 100 to one vs water. So relatively speaking, fat shows poor selectivity, but if you deliver heating and cooling right, there is some selectivity for fat absorption.

Other Key Points

With regards to cooling and heating, we always want to preserve the epidermis and a dynamic cooling device can do so. It is also important to know the photochemistry with regards to chemical reactions and pay attention to these reactions; an example of this can be seen with patients who have previously been on Gold.

Microwaves and Radiofrequency

Microwave and radiofrequency devices are becoming increasingly commonplace within our armamentarium. They rely on heating water, the resistance of water molecules turning causes heat. The  microwave device is around 6GHz. Problems like underarm sweat can be treated with systems like MiraDry. Basically what happens is that the microwaves come down and there is a discontinuity of the dermal-fat junction and it heats up the sweat glands about 4mm below the skin. MiraDry offers another application in clinical practice and can complement other procedures. It also has little downtime.

We are going to begin to see more and more radiofrequency (RF) reactions. It is important to understand SAR, i.e., the specific absorption rate at which energy is absorbed when exposed to an RF electric field. By delivering the right time and the right temperature, one can establish very nice reliable heating of the skin.

 

MauiDerm News Editor- Judy Seraphine

 

 

Pediatric Dermatology: What we’ve learned that has changed the way we think about and practice medicine

Sheila Friedlander, MD and Ilona Frieden, MD

Part 1: Look What the Wind May Have Blown In

Dr Friedlander began this session with a case study….A child presents to your office with an unusual rash.  The pediatrician called it maculopapular,  others migth call it polymorphous. The rash is papular ,  erythematous and fairly generalized.  Dr Friedlander states that most of the time when a child comes into your office with this type of rash, the history is often not that helpful. Be sure to ask about systemic signs, fever, or anyone else sick in the house.  Obtain a drug exposure history. . What is it reasonable to think about? Most of the time, it is a virus. Enterovirus is a reasonable possibility When in doubt, some physicians will blame EBV, especially if the child has had amoxicillin. Occasionally, it could even be measles with this sort of polymorphous eruption,  so it is important to look for cough, coryza, and conjunctivitis. It could also be Parvo virus so check to see if the  child had “slapped cheeks” appearance at any point, or a lace-like appearance to the body rash. . This particular child has had high  fevers for four days and the family is starting to get anxious.  The patient is fussy and his  lips are cracked. The parents also inform you that the child took amoxicillin two days ago and some NSAIDs yesterday. What do you think this is?  Dr Friedlander again emphasizes that it is important to go through his history of drug exposure;  fortunately  in this case, the rash predates any medications.

When you examine the eyes, you note the conjunctiva are red with a rim or halo of white around the cornea,, which is called limbal sparing—In  the diaper area, there is superficial desquamation that is really faint superimposed on confluent erythema. .  What can cause superficial desquamation in this pattern. What about staph scalded skin? The kids who have staph scalded skin do have intertriginous area involvement, but also often have erythema  in the perioral and periorbital areas along with radiating fissures around the mouth. They may also have blisters or bullae.

When you see a patient like this, you need to think about virus, drug, and staph scalded skin. Remember, this child has a polymorphous rash, has lip and tongue involvement, and a very distinctive diaper-area rash that developed  early in his course. The child also has conjunctivitis with limbal sparing and one enlarged lymph node.

So, what should we be  thinking about? Kawasaki Disease…Dr Friedlander reminds us to consider this whenever we see a child who has had prolonged fever  and a rash.

A 2013 article by Bayers S, et al was published in the JAAD, and is an extremely useful review  for dermatologists interested in  Kawasaki Disease. This disease is a small and medium size artery vasculitis.  One of the diagnostic criteria is fever for more than five days; however, if you have a child that fits all of the criteria at day four, you should move ahead with treatment. The earlier you start intervention, the less likely the child is to develop coronary artery disease. The palms and soles are  often red and swollen, and the aforementioned findings of conjunctival injection along with crusted lips and oral mucous membrane erythema are often present.  Cervical l adenopathy is often present but usually asymmetrical—this is helpful to remember.  If you suspect Kawasaki disease, get an expert in the area to help you manage this patient.

What are other KD  skin findings that are of interest to dermatologists?

  • Micropustular follicular rash (uncommon)
  • Nail discoloration, onychomadesis
  • BCG site rash
  • New onset psoriasis

Kawasaki Disease: Epidemiology

The typical age at presentation is six months to five years of age and the highest incidence of the disease is in Asian countries. In the United States, the highest incidence is among those of Asian ethnicity. If a child has this disease, the risk for a sibling to develop the disease is six to 30 times higher than normal and  for any progeny of KD patients, , the risk for his/her child is two times higher. The recurrence rate is two to four percent.

Why is this disease so important? Coronary artery aneurysms and cardiac disease!

It is extremely important to make the diagnosis because cardiac complications can occur. These include:

  • Coronary ectasia and aneurysms
  • Decreased coronary arterial compliance
  • Myopericarditis
  • Arrhythmias
  • Ischemic heart disease
  • Pericardial effusion
  • Valvular regurgitation
  • Myocardial infarction
  • Sudden cardiac death

Cardiac complications affect 15 to 25 percent of untreated patients.

Treatment for Kawasaki Disease

Again, refer to a specialist to help manage these patients. Treatment can decrease coronary risk by at least a factor of five. Treatment includes IVIG 2gram/kilogram over 12 hours, ASA High (80-100mg) divided qid, then low-dose (3-5mg) around day 14. Corticosteroids may be useful in refractory patients. Biologics, such as infliximab and etanercept, may also be useful. IVIG should be repeated if there is no defervescence at 36 hours.

What causes this disease?

We know that cases tend to occur close to each other temporally and there is a prediliction for winter and spring. It occurs mostly in children and is self-limiting. It takes a  course similar to that of  infectious processes  where  immune-mediated response is apparent. Lots of organisms  have been implicated; yet the etiology remains elusive..

Over the last  few years, researchers have found that a correlation exists between wind currents that track from Asia to Japan which  traverse the North Pacific and the occurrence of Kawasaki disease. There have been three epidemics in Japan in May, March, and April, which correlate with times of highest intensity wind currents The belief is that there may be a wind-borne environmental trigger. Investigators are now utilizing  planes and are collecting samples of air in the middle of these wind currents. Many scientists believe that there is a wind-borne agent that is causing this disease. Stay tuned, we may have more information next year.

Part 2: What is a Birthmark?

In the broad sense, a birthmark is a developmental anomaly that is present on the skin. As you know, they do not necessarily need to be present on the day of birth and they can range from common to rare.

Dr Frieden discusses the six questions that you should ask when you see a child with a birthmark.

  • What is the diagnosis? Is this a port wine stain or is this a premonitory mark of an infantile hemangioma. It is extremely important to pin down the diagnosis.
  • Is there a risk of extracutaneous associations?
  • What is the prognosis/natural history?
  • What (if anything) needs to be done? Are there good treatments?
  • Is there a “window of opportunity?”—an example of this would be infantile hemangioma whereby early intervention can really make a difference if treatment is needed
  • What is the cause?

Dr Frieden has been a pediatric dermatologist for a little over thirty years and she states that parents always ask: “what caused this?”  Previously, the answer was “we don’t know”.  Often times, especially for mothers, they ask themselves if they did something wrong during the pregnancy.

So to answer the sixth question, according to Dr Frieden, “2013 has really been a watershed year.”  Researchers are now using deep sequencing of birthmark tissue, not germ-line DNA in order to understand the genes that cause birthmarks. Most of the birthmarks that appear are post-zygotic somatic mutations. Knowing the cause of the birthmark may help to pave the way for newer therapies.

In 2013 Mutations In….

  • GNAQ cause Sturge-Weber
  • KRAS and HRAS causes of nevus sebaceous
  • NRAS cause of giant nevi
  • GTPase BMS1 cause of familial aplasia cutis congenital (germ-line)

What’s exciting about this? New therapies will be developed to address activating mutations because these are also mutations that can cause cancer. We know that researchers are looking for ways to stop activating mutations in these pathways. So you may ask “how does this affect a birthmark?” Dr Frieden provides an example where it may be very important and that is in Sturge-Weber. In Sturge-Weber, children are generally born with Sturge-Weber and they are neurologically normal, there are exceptions to this; however, Sturge-Weber is really a progressive disease. Children will develop heavy paralysis and seizure disorder despite the fact that they are normal at birth. It may be that if we treated these patients with something that inhibited an activated mutation GNAQ only for a couple of years, for example, we may be able to avoid some of the developmental changes that occur. Scientists don’t really know whether or not this is true, but it is an example of where we may be able to halt progression. This is an incredibly exciting time because, as physicians, we may be able to look parents in the eye and provide them with some information about the cause of the birthmark.

Part 3: Drug Reactions in Kids

This section of the presentation focused on drug reactions.,foc. Why is Dr Friedlander cautious when prescribing  minocycline? There is more and more evidence that minocycline is one of the offenders that can cause Drug Reaction Eosinophila and Hypersensitivity Syndrome (DRESS). It’s important to be aware of this disorder and how frequently we can see it.  It  can occur in one in 1,000 to 10,000 drug exposures. DRESS can be distinguished from other drug reactions in that often times the onset is later, approximately two to six weeks after exposure. It presents with a morbilliform rash, significant facial and periorbital edema, and exfoliative changes. Why is it of concernt? DRESS can affect the liver and other organs and has a mortality rate of up to ten percent. This is a good discussion to follow in that of  Kawasaki Disease because they share a similar differential diagnosis. Patients with DRESS have bilateral, significant cervical adenopathy, there may also be significant facial edema, and  often have what looks like an extensive erythematous, sometimes edematous,  confluent eruption. Husain Z, et al published a very useful review in the JAAD in 2013 regarding clinical perspectives and management and therapeutics for DRESS syndrome.

What are the drugs that we need to worry about?

When considering  DRESS, you want to check to see if the patient has eosinophilia and/or liver involvement because such findings raise the likelihood of life-threatening complications. . The common drugs associated with this problem are outlined below:

Ped 1

 

Pathogenesis

We now know that there are some genetic polymorphisms for drug metabolism that DRESS patients may exhibit. For many of these patients, there may be a genetic difference in how these drugs are metabolized which may be a cause of the disease.  There are two enzymes that have been implicated, epoxide hydroxylase and glutathione transferase. Another fascinating discovery is the association between DRESS and  human herpes virus (HHV-6), CMV, or EBV. Researchers are really not sure whether or not this a secondary involvement, but some scientists feel that re-activation may play an important role. In fact, there are some studies that have demonstrated that those who receive amoxicillin are worse prognostically because amoxicillin, at least in vitro, can help encourage activation and replication of HHV-6. This is an interesting combination of environmental and immune reactions. A number of specific genetic markers have been identified: these include  HLA-A 3101 in association with  carbamazapine; HLAB-5801 with  allopurinol; and HLA DR3 and HLADQ2 with  carbamazapine that put certain patients at risk.

What organ is likely to be involved if your patient gets DRESS?

Ped 2

 

Don’t forget to think about the differential diagnosis. Remember that the interval before onset is longer than Stevens Johnson Syndrome and TEN. Organ involvement is also more common in DRESS. These patients also tend to have more facial swelling and symmetrical nodes as opposed to Kawasaki Disease. If you were to perform a biopsy in these patients, you would see a more predominant  lymphocytic infiltration whereas in  Stevens Johnson Syndrome or TEN you would see a predominance of necrosis.

What can you do if you think your patient has had a reaction to DRESS?

First and foremost, you want to discontinue the drug. . You can also do skin or serum testing; this  provides a positive predictive value; however, it is not widely used. Therapy for DRESS includes supportive care, systemic l corticosteroids if there is liver involvement, and avoiding the use of antibiotics or NSAIDs.

Prednisone 1mg/kg/day  is often utilized, and tapered slowly over three to six months. If there is no response, patients can be given IV methylprednisolone 30mg/kg IV qd for three days. Do not stop these kids abruptly as there  relapse can occur. It is also very important to check thyroid function.

Dysphagia

Some experts believe that ysphagia is an early manifestation of DRESS syndrome and it may come before the rash. Why is this important? Many times children will present to  the pediatrician with a sore throat and will be given amoxicillin empirically. With the advent of rapid Strep tests, Dr Friedlander would encourage all pediatricians to utilize these tests before simply prescribing amoxicillin, as we know that there is a suggestion that it may be detrimental to patients with evolving DRESS.. Dr Friedlander also recommends antipyretics with Tylenol versus NSAIDs. Remember to ask if the patient is feeling uncomfortable or having trouble swallowing.

MauiDerm News Editor-Judy Seraphine

Pediatric Dermatology: What we’ve learned that has changed the way we think about and practice medicine (continued…)

Sheila Friedlander, MD and Ilona Frieden, MD

Part 4: Hemangiomas and the Use of Beta-Blockers

Propranolol

In this section, Dr Frieden discusses the use of propranolol for the treatment of infantile hemangiomas. A consensus report, published in the Journal of Pediatrics in January of 2013, discussed the initiation and use of propranolol for infantile hemangiomas. Dr Frieden was a co-author on this publication and believes that it may have an affect on the way in which we practice medicine.  The background to this report is that there was a tremendous amount of diversity among the users of this medication. When there is not a lot of data available, the idea of a consensus is to try to come to a central point with general recommendations.

Is hospitalization needed?

The consensus group, comprised by a variety of specialists, recommended inpatient hospitalization if the patient is less than eight weeks old or less than eight weeks adjusted gestational age, and if the patient has other “high-risk” medical conditions. Patients older than eight weeks should receive outpatient monitoring, using heart rate and blood pressure, with dose escalation. Monitoring should be performed one to two hours after dose escalation as great as 0.5mg/kg/day. In Dr Frieden’s practice, she finds that blood pressure monitoring can be difficult with infants; however, heart rate monitoring is easily doable and just about anyone can do this, including parents.

Is EKG needed?

A consensus was not achieved on the use of ECG for everyone.  One may; however, consider ECG in the following circumstances:

  • HR is below normal for age
    • Newborns (<1 month old), <70 beats per minute,
    • Infants (1–12 months old), <80 beats per minute, and
    • Children (>12 months old): <70 beats per minute.
  • Family history of congenital heart conditions or arrhythmias (eg, heart block, long QT syndrome, sudden death); maternal history of connective tissue disease
  • History of an arrhythmia or an arrhythmia is auscultated during examination

The consensus group developed an algorithm that you can utilize or recommend to your pediatric colleagues regarding the initiation of treatment.

Key Take Home Points

In March of 2014, propranolol was approved for the treatment of infantile hemangiomas at a dosage of 3mg/kg/day. A randomized trial demonstrated a 60 percent clearance; however, in systematic reviews, the response rate of propranolol is in the range of 90 to 97 percent, although not everyone achieved clearance. Significant uncertainty and divergence of opinion still exist regarding the safety, monitoring, and dose escalation of propranolol. If the child is at risk for PHACE, at the minimum, you should perform an echocardiogram before considering initiating propranolol. Remember that the peak effect of the medication, in terms of cardiovascular effects, occur one to three hours after administration. The dose response is most pronounced after the first dose and it is extremely important to recheck the heart rate with dose escalation greater than 0.5 percent mg/kg/day. Hypoglycemia is the most common, serious complication. You should discontinue the medication during intercurrent illness, especially with decreased oral intake.

Topical Beta-Blockers

If you are concerned about hypoglycemia and other potential side effects, topical therapy may be a viable option.

What’s the evidence with regards to timolol? There are many citations supporting the safety of  timolol with minimal to no toxicity reported. Most dermatologists have found it useful for thin facial and hand lesions; however, there are some data that support its use in focal, deep facial lesions. A randomized controlled trial demonstrated that timolol 0.5 percent gel twice a day  was a safe and effective option for small superficial infantile hemangiomas that have not ulcerated and are not on mucosal surfaces.

There have been some recent concerns regarding potential toxicity of  timolol when utilized on ulcerated lesions, mucous membranes, or when used extensively in small premature infants.  as it may be absorbed and lead to  systemic levels of drug that could be problematic. Dr Friedlander and her colleagues are currently conducting a study at UCSD investigating  this issue.

Many experts suggest utilizing the drug sparingly, not more than  one to two drops twice a day, particularly in  micropreemies.

Part 5: Vascular Birthmarks and Overgrowth

A 2013 article by Lee MS, et al published in the JAAD reconfirmed Dr Frieden’s approach to the management of vascular birthmarks and overgrowth. Vascular stain and overgrowth were previously lumped together as “Klippel-Trenaunay.” As far back as 2004, Dr Frieden and her colleagues were able to report that the geographic stains had much higher morbidity and a much poorer prognosis. Many cases that were previously diagnosed as CMTC actually reticulate port wine stain. So, how do we give accurate prognostic information to patients and families?

It is important, as clinicians, to distinguish geographic from blotchy/reticulate stains. Conduct serial leg measurements if stains involve the lower extremity and measure head circumference. It is also imperative to look for dysmorphic features, e.g, syndactyly and facila dysmorphism. If dysmorphic features are present, you should consider rare Vascular Stain/Overgrowth syndromes.

Pediatric Dermatology Summary

  • Don’t forget about Kawasaki Disease—maybe the wind blew it in??
  • Birthmarks aren’t necessarily present at birth- and we now sometimes know the associated mutation
  • Dysphagia is an early symptom in DRESS
  • Propranolol is the drug of choice for most problematic infantile hemangiomas and treatment guidelines exist
  • Timolol for children is A-OK