Medical Dermatology – Page 5

Cutaneous Oncology: Talking Points

June 27, 2014

Marc Brown, MD

Here are some of the key points from Dr Brown’s presentation at MauiDerm NP+PA Summer 2014….

High risk parameters for BCC include location on the central face, larger size, recurrence, prior radiation and aggressive histology.

High risk histology for BCC includes the following: infiltrating, morpheaform, micronodular, basosquamous, sclerosing, desmoplastic, and perineural invasion.

Risk factors for the development of SCC include: UV light exposure, X ray exposure, HVP infection, immunosuppression, chronic non-healing or inflammatory wounds, an rare genetic syndromes.

High risk locations for SCC are ear, lip, genitalia and scalp.

Other risk factors for aggressive SCC include: poorly differentiated histology, depth of invasion, perineural invasion, size (greater than 2 cm.).

Emerging Therapies in Psoriasis: Clinical Pearls

June 27, 2014

Bruce Strober, MD, PhD

What’s new in the field of psoriasis? Dr Strober provides us with some clinical pearls…

TNF-inhibitors cause weight gain.
Ustekinumab does not cause weight gain.
IL-23 inhibitors block p19 and are more specific than IL-12/23 inhibitors, which block p40.
Apremilast achieves PASI75 in approximately 30% of patients after 16 weeks.
IL-17 pathway inhibitors achieve PASI75 in approximately 80% of patients after 12-16 weeks.
IL-17 pathway inhibitors may slightly increase the risk of mucocutaneous candidiasis.
JAK kinase inhibitors will require monitoring for liver function, renal function, lipids and creatinine phosphokinase.
JAK kinase inhibitors might increase the risk of varicella zoster infection.
Apremilast treats psoriatic arthritis.
Apremilast does not need laboratory monitoring.

Pediatric Dermatology: Clinical Pearls

June 25, 2014

James Treat, MD

1. Coxackie Virus can superinfect atopic dermatitis and look similar to eczema herpeticum

2. Kwashiorkor can mimic severe atopic dermatitis in patients with severe nutritional restrictions

3. Scabies almost never affects the face in children over two years of age

4. Mycoplasma can cause mucosal predominant stevens johnson with little to no skin lesions

5. Drug reaction with associated fevers are much more concerning and should be evaluated promptly

10 Pearls from Dermatopathology – The Biopsy, Analysis & Report

June 25, 2014

Whitney J. High, MD, JD, MEng

Dermatopathology is one of two ABMS-recognized subspecialties in dermatology, and one may become fellowship trained after first being a board-certified dermatogist or general pathologist.
Biopsy use is increasing. In nine geographic areas of the USA, over the time period 1986-2001, the biopsy rate among those >65 years of age rose 2.5-fold, and the melanoma rate rose 2.4-fold.
There are multiple steps involved in taking a specimen from a piece of “wet” tissue, in formalin, to an interpretable slide and to a typewritten report. These steps include:

The dermatopathologist is examining but a small portion of your original sampling, and this must always be considered when one assesses the “representative nature” of the results.
There is an old mantra in pathology in general: crap in = crap out. No dermatopathologist, regardless of skill or expertise, can weave a poor sampling into an outstanding result.
It is the clinician responsibility to secure a “representative biopsy”, and if this is not done, eventually, this inadequacy will be discovered. Over the period of 1998-2005 the number of shaves increased but the volume of shaves decreased.
The technique employed (shave, punch, excision) must be adapted to the clinical situation – there are no fixed rules that may be applied to every situation. This is why the clinician is being paid an “evaluation/management” code; namely, to select a biopsy that is appropriate for the circumstances.
A recent study of pigmented lesions showed the odds of misdiagnosis (overall and associated with an adverse outcome) were much higher with a punch biopsy than with an excisional biopsy, whereas a shave biopsy was only weakly associated with misdiagnosis. (Ng et al. 2010)
Situations where the biopsy technique should be carefully considered include suspected:

The pathology report itself should be carefully read and scrutinized to understand precisely what the dermatopathologist is trying to convey. Demographic data should be confirmed. The technique and specimen size should be verified. Data used by the dermatopathologist to formulate the diagnosis should be noted (i.e., step levels, immunostains, special stains, etc.). If questions still exist, a phone call should be placed to the dermatopathologist for expanded dialog.

Eruption! Pediatric Acne

June 11, 2014

Larry Eichenfield, MD

Dr Eichenfield provided the audience at MauiDerm 2014 with an update on the new pediatric guidelines for the management of acne. These guidelines, published in May of 2013, were developed by the American Acne and Roseacea Society and endorsed by the American Academy of Pediatrics, which is the first time that the Academy has a set of guidelines for the management of acne. One of the main reasons this was done was to address the practice gap between dermatologists and pediatricians. The group of experts was comprised of dermatologists with expertise in acne, pediatric dermatologists, and pediatricians.

As we know, acne ranges in terms of presentation and severity. Acne can be categorized by age, i.e., neonatal (0-6wk), infantile (0-1), mid-childhood (1-7), preadolescent (7-12), and adolescent (12-19).

Dr Eichenfield emphasizes that mid-childhood acne (age 2 – 7) acne is the most worrisome. It can be associated with premature adrenarche, Cushings Syndrome, CAH, gonadal/adrenal tumors, and precocious puberty. Mid-childhood acne is very uncommon, and is a sign of early adrenarche, often associated with a pathologic process. The assessment for mid-childhood acne includes assessment of testicular size (males), presence or absence of hirsutism, clitoromegaly, androgenetic alopecia, increased muscle mass, and/or deepening of the voice (males). Tests and examinations include a growth chart, evaluation including bone age, tanner stage, Total/Free testosterone, DHEAS, androstenedione, LH, FSH, prolactin, and 17OH-progesterone. The guidelines suggest that you should refer these patients to a pediatric endocrinologist.

What do the new guidelines say?

It’s important to know that pre-adolescent (7 ≤ 12 years) acne is common and may precede other signs of pubertal maturation. Work-up beyond history and physical is generally unnecessary unless there are signs of androgen excess, polycystic ovarian syndrome, or other systemic abnormalities. According to the data, there is evidence that acne, and possibly puberty, are now occurring at an increasingly earlier age for both males and females. If you look at some of the papers that were published about a decade ago, the amount of comedones that were seen in a ten or 12 year-old then is probably different now. Twelve is no longer an age point defining “normal acne;” if you are eight and above acne can be typical and common.

After the guidelines were published early acne in preteens was highlighted in several newspaper articles, and radio and television segments. Articles were published in both the New York Times and USA Today. In fact, after the New York Times article was published, there were over 157 blogs that provided an interesting perspective comparing what the general public thinks regarding acne and what we do as specialists. A recent analysis of the National Ambulatory Medical Care Survey (NAMCS) database assessed trends in the age of children seeking treatment for acne. NAMCS data from 1979 through 2007 were analyzed for all physician visits in which acne vulgaris was listed as a diagnosis in children aged 6 to 18. The analysis revealed a significant decrease in the mean age of children seeking treatment for acne over this period.

Over the past several years, clinicians have noted an earlier onset of acne—that is, the appearance of acne in patients as young as 8 or 9 years. Indeed, it has been suggested that 12 years of age should no longer be considered the low end of the “normal” range for the onset of acne.

Acne may be the first sign of the onset of puberty in children aged 7 to 11 years. The general clinical impression of earlier puberty is, in fact, supported by epidemiologic data in the US and elsewhere. In general, the trend toward earlier puberty is stronger among girls than among boys. In any event, the earlier onset of acne has mirrored the downward trend in puberty timing.

The guidelines provide an algorithm for the management of pediatric acne. If you can generally categorize the acne as mild, moderate or severe, you can access the algorithm. Keep in mind that this algorithm is slightly different than prior guidelines, in that for mild acne initial treatment benzoyl peroxide, based upon the evidence, made it as one potential, initial solo therapy. The guidelines can be found in the Journal of the American Academy of Pediatrics, or online at: http://pediatrics.aappublications.org/content/131/Supplement_3/S163.full.pdf.

Acne Guidelines: Highlights

The guidelines emphasize appropriate use of medications based upon disease severity. Oral antibiotics should be used concurrently with a topical retinoid because it is important to build a topical regiment to “transfer the patient to” after a limited course of antibiotics. A variety of studies show that 70 percent of the time you can transition your patient who is on an oral antibiotic and topical retinoid to a regiment of topical retinoid alone or combinations with topical antimicrobials (like benzoyl peroxide) and/or antibiotics

Topical retinoids may be used as monotherapy or in combination products and in regimens of care for all types and severities of acne in children and adolescents of all ages. It is important to remember that topical antibiotics are not recommended as monotherapy and if a topical antibiotic treatment is to be used for more than a few weeks, topical benzoyl peroxide should be added, or used in combination products. The guidelines also suggest that fixed-dose combination topical therapies may be useful in regimens of care for all types and severities of acne.

With regards to oral antibiotics, they are a reasonable approach for moderate to severe inflammatory acne vulgaris at any age. Tetracycline derivatives should not bee utilized in children 8 years of age and below. Second generation tetracyclines are “sometimes preferred” to tetracycline because of ease of use, fewer problems with absorption with food and minerals in vitamins and other supplements, and less frequent dosing. It’s very important that patients are educated and monitored for potential adverse events when utilizing oral antibiotics for acne.

Hormonal therapy is actually interesting because there are people who are very pro-hormonal therapy and others are a bit more conservative and prefer oral antibiotics. The group ended up stating that combined oral contraceptives (OCs) may also be useful as second-line therapy in regimens of care in pubertal females with moderate to severe acne; however, tobacco use and family history of thrombotic events should be assessed. Due to concerns about growth and bone density, many recommend withholding OCs for acne until one year after onset of menstruation.

Isotretinoin is recommended for severe, scarring, and/or refractory acne in adolescents and may be utilized in younger patients. Remember that extensive counseling, particularly regarding the avoidance of pregnancy, as well as careful monitoring of potential side effects and toxicities, is recommended. As far as the specific discussion on isotretinoin in pediatric use, there are bone mineralization changes; however, the data is inconsistent and it is not associated with increased factures. Hyperostoses are very uncommon for acne and there has been one case of premature epiphyseal closure in a patient on isotretinoin for acne, but that’s not necessarily attributable to the isotretinoin. IBD is controversial, but counseling is reasonable.

Practice Gaps

Dr Eichenfield states that there is a chasm in the way that General Practitioners, Pediatricians, and Dermatologists treat acne. A 2014 paper by Tan et al showed that topical retinoids were prescribed in 41 percent of acne visits. Older age, male gender and having Medicaid insurance were associated with a lower likelihood of receiving a topical retinoid prescription. Moreover, the researchers found that in the Medicaid dataset, patients who saw a pediatrician or general practitioner had lower odds of receiving a topical retinoid prescription versus those patients who saw a dermatologist.

Another study looked at the National Ambulatory Medical Care Survey (NAMCS) data regarding the treatment of preadolescent acne in the United States. The data were stratified according to age group and physician specialty. The findings are presented below:

What are Dr Eichenfield’s thoughts on the practice gaps?

Over-reliance on oral antibiotics
Use of oral antibiotics without BP
Use of oral antibiotics without Retinoid
Use of topical and oral antibiotics together, without retinoid
Under appreciation of early, significant acne as predictor of worse acne over time

Literature has shown that early comedonal acne may predict later severe acne. So remember that if you see a patient with a high number of comedone counts at an early age, their chances of severe inflammatory acne at a later age is much higher than someone who has low comedone counts early on.

Another issue that Dr Eichenfield is appreciating more and more in clinical practice is that you can have very early, subtle scarring. We know that there is a lot of scarring that occurs without nodular-cystic disease, so this is very common. This is an important to try to get patients evaluated early so that scarring can be prevented, and minimized. Dr Eichenfield advised that a useful technique is to side-light the face and look for depressions in the face, displaying scarring as opposed to post-inflammatory hyperpigmentation or persistent erythema.

A study by Patel and colleagues aimed to determine what types of acne lesions preceded the development of atrophic acne scars. Twenty-two patients with mild to moderate acne were enrolled in a split-face study in which one side was treated with non-ablative laser and the other remained untreated. A series of standardized digital facial photographs was obtained from the untreated side at 2-week intervals from baseline to week 12, and all photographs in the series were aligned with the baseline photo. When all of the atrophic scars were tracked to baseline, 53 were found to have arisen from clinically normal skin, 30 were established scars, and 21 arose from acne lesions, including closed comedones. However, no open comedones at baseline corresponded to atrophic scars. The results of this study not only verify that inflammatory acne lesions often lead to atrophic scarring, but also demonstrate that acne scars may arise from initially comedonal lesions, as well as from clinically normal skin. Moreover, they indicate that a period of 12 weeks is sufficiently long to develop and establish atrophic scars. Thus, aggressive treatment of both inflammatory and comedonal acne is warranted to minimize acne scarring.

What about Isotretinoin?

We know that isotretinoin is the most effective treatment for acne; however, the optimal dosing regimen is still unknown. Dr Eichenfield comments that he uses isotretinoin commonly. He also states that he tends to be biased towards lower-dose isotretinoin on a daily basis, working up to cumulative doses of 120-150 mg/kg. He commonly will the daily doeses up to the “highest comfortable dose,” that is, the highest dose with minimal significant side effects or laboratory abnormalities.

A recent publication looked at 180 patients with acne resistant to other treatments who were enrolled in an observational, prospective study of istotretinoin with cumulative doses less than to 220 mg/kg versus isotretinoin greater than or equal to 220 mg/kg. Of these patients, 116 participated in the 12-month follow-up survey. At that time, 97.4 percent of the patients reported that their acne was improved. Overall, acne in 32.7 percent of the patients in the study relapsed at 12 months, and 1.72 percent of the patients required a retrial. In the lower-dose treatment group, the relapse rate was 47.4 percent compared with 26.9 percent in the high-dose group. Almost 100 percent of the patients in both treatment groups developed cheilitis and xerosis during treatment. Retinoid dermatitis was significantly more common in the high-dose treatment group and none of the other adverse effects were significantly different between the two groups. However, it should be noted that in the higher dose group, nine patients had persistent muscle aches, eight patients had persistent joint aches, and two patients had hearing changes. (Blasiak RC et al. JAMA Dermatol 2013;149(12):1392-1398) Also of importance with regards to this study are the laboratory abnormalities based upon the dosing. (See table 1)

Dr Eichenfield states that this publication has yet to “move him” to abandon his current methodology with regards to isotretinoin dosing for this patients.

Idiopathic Facial Asceptic Granuloma (IFAG) and Childhood Rosacea

We have seen a very interesting change in perspective regarding this disease. Occasionally, we see these patients who present with lumpy, cystic-type lesions, separate from acneiform lesions. A multi-center study of four French dermatologic centers looked at patients who were diagnosed with IFAG between October 2000 and July 2007. Thirty-eight patients were included in the study. The median age at the time of diagnosis of IFAG was 43 months, with a median follow-up of 3.9 years. Sixteen patients (42.1%) had at least two criteria of childhood rosacea, 11 of 32 (34.4%) with a single lesion and 5 of 6 (83.3%) with multiple lesions. Remember that childhood rosacea presents with flushing, permanent or recurring erythema, papules and postules without comedones or microcysts, convexity predominance of lesions, ocular rosacea (chalazions, conjunctival hyperemia, keratitis). (Prey S, Ezzedine K et al. Pediatric Dermatology 2013;30:429-32)

What does this mean to us? Children with IFAG are at risk for childhood rosacea, and follow-up is advised, including periodic ophthalmologic assessment.

MauiDerm News Editor- Judy Seraphine

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

April 30, 2014

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

Contact Dermatitis: Clinical Pearls

April 15, 2014

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

April 7, 2014

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.

Mypatchlink.com 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.

Summary

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

Psoriatic Arthritis Update

March 20, 2014

Arthur Kavanaugh, MD

Dr Arthur Kavanaugh is a Rheumatologist and a Professor of Medicine at the University of California, San Diego. At MauiDerm 2014, he provides the practicing dermatologist with an update on PsA and the latest treatment advances…

The reported estimates of the prevalence of PsA among psoriasis patients have been highly variable, i.e., six percent to 42 percent. It is currently estimated that between 20 and 30 percent of psoriasis patients also have PsA. In addition, psoriasis precedes PsA in over 85-90 percent of the cases, though we’re not sure why. Dr Kavanaugh believes that in 20 to 30 years, we may have that answer. In 2012, there were an estimated 1,600,000 PsA patients in the United States. Of those patients, about 485,000 were diagnosed and only about 345,000 received treatment. Now that we have treatment available, Dr Kavanaugh feels that healthcare providers will be seeing more of these patients. As dermatologists, it is important to remember that PsA is a serious condition; approximately 20 percent of patients with PsA will develop destructive, disabling arthritis. PsA results in radiological damage in up to 47 percent of patients at a median interval of two years. Remember that other comorbididites often exist among PsA patients; these include, metabolic syndrome, CAD, uveitis, IBD, impaired function and quality of life, and economic implications.

Recent data presented at the 2013 American College of Rheumatology, suggest that a delay in the diagnosis of PsA correlates with poor patient outcomes. A study of 283 PsA patients, fulfilling the CASPAR criteria, demonstrated that even a six-month delay from symptom onset to the first visit with a rheumatologist contributed to the development of peripheral joint erosions, sacroiliitis, and worse long-term physical function.

Diagnostic Criteria for PsA (CASPAR)

The diagnostic criteria for PsA includes an established inflammatory articular disease (joint, spine, or entheseal), plus three or more points from the following five categories:

Psoriasis
- Current-psoriatic skin or scalp disease present today (2 points)
- History-a history of psoriasis
- Family history-history of psoriasis in a first or second degree relative
- Nail Changes-typical psoriatic nail dystrophy
- A negative test for RF-by any method except latex (preferably ELISA or nephlemetry)
- Dactylitis
  - Current-swelling of a current digit
  - History –history of dactylitis
  - Radiological evidence of juxta-articular new bone formation-ill-defined ossification near joint margins (but excluding osteophyte formation) on plain X-rays of hand or foot

The CASPAR criteria are very sensitive and very specific; but, in the clinic, the question lies as to whether or not the patient has inflammatory arthritis. That is a tougher question and we don’t have a perfect answer for that. Several questionnaires and screening tests have been developed for this, such as the Psoriasis Epidemiological Screening ProjecT (PEST), Toronto Psoriatic Arthritis Screen (ToPAS), and Psoriatic Arthritis Screening and Evaluation (PASE). All of these instruments did relatively well in the development studies; however, remember that with these screening tests come trade-offs. The more sensitive an answer is, the less specific it is and vice versa. There is no perfect questionnaire and how they perform is based upon how you define them. The difficulties are the oligoarticular and differentiating osteoarthritis from inflammatory arthritis. The utilization of more sensitive imaging (ultrasound and MRI) can help to determine what is inflammatory versus what isn’t inflammatory.

GRAPPA PsA Treatment Recommendations

The chart below outlines the GRAPPA treatment recommendations; however, these guidelines are currently being updated to incorporate some of the newer treatment modalities.

Treatment choices are based on the severity of the different domains.

Clinical Pearl-PsA requires a clinician to really listen to the patient, examine the patient, and formulate and appropriate treatment plan with the patient.

We know that the data on the TNF blockers for the treatment of PsA is very positive for both joint symptoms and skin symptoms. Currently, we even have data that demonstrate the effects of TNF blockers on issues that are important to the patient, such as nail involvement, enthesitis, and dactylitis. In the past, we didn’t have we didn’t have quantifiable ways to measure these, but now we do.

Data also demonstrate that TNF inhibitors slow down the damage to the bone. Getting patients under good control allows them to be functional and go about doing the things they do in their daily life.

Certolizumab Pegol

Certolizumab Pegol (CZP) was approved for the treatment of PsA in September of 2013 and is the fifth TNF inhibitor available for the treatment of PsA. The RAPID-PsA study is important to us, as clinicians, because the researchers looked at switching, i.e., may have failed a previous TNF inhibitor. The phase III results of the 24-week, double-blind, placebo-controlled study showed that the ACR20 response at week 12 was significantly higher in the CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (58.0% and 51.9% vs. 24.3%) and PASI75 response at week 24 for patients with ≥ three percent psoriasis body surface area at baseline (61.6% randomized set) was 62.2 percent with CZP 200mg Q2W and 60.5 percent with CZP 400mg Q4W versus 15.1 percent with placebo. This data demonstrate that CZP is effective in PsA, including patients with prior TNF inhibitor exposure. This is very important for our patients who may not have responded to previous therapy. This data as also been confirmed in other registries; therefore, indicating that switching from one TNF inhibitor to another in PsA is a viable option.

In PsA, we don’t know whether a TNF inhibitor plus methotrexate (MTX) is additive or synergistic. In Rheumatoid Arthritis, there is data that demonstrate that even a dose of MTX as low as 10mg gets you synergy. This is something that as a practitioner, you need to negotiate with your patients.

What about obesity and weight loss?

Currently, the data on obesity are very strong and very consistent. We know that PsA patients have shown an increased prevalence of obesity. A study by Di Minno and colleagues demonstrated that within 12 months of starting a TNF inhibitor, patients with PsA achieved minimal disease activity (MDA). The prevalence of obesity was lower in the group achieving MDA. Patients who lose weight and then begin a TNF inhibitor have a much better chance of doing well, than those who are obese. When you look at the CORRONA database, a study of 392 patients starting a TNF inhibitor showed that only obesity was significantly associated with the discontinuation of treatment. This tells us that patients who are obese do not do as well on therapy and have more disease activity. This is true not only for fixed-dose treatment, but weight-based treatment, such as infliximab, as well. Obesity is inflammatory and this is a very dramatic effect. In fact, it has changed the way Dr Kavanaugh approaches his patients regarding discussing the importance of weight loss.

Biosimilar (CT-P13)

A randomized, double-blind, phase III study of 606 patients demonstrated the clinical equivalence of CT-P13 to infliximab when co-administered with MTX in patients with active rheumatoid arthritis. The results were maintained after the switch from infliximab to CT-P13 from weeks 52 to 104. CT-P13 received a favorable opinion by the EMA and is now available in Europe. CT-P13 was studied in rheumatoid arthritis and ankylosing spondylitis and because it was clinically equivalent it received approval for all of the indications for which infliximab is approved. The FDA has not yet weighed in on how it will approach biosimilar approvals; however, they are here and this is coming. Cost is a major issue, i.e., they could be available at 20-25 percent less than the branded products.

Emerging Therapies

We know that TNF inhibitors work well in GI disease, skin disease, rheumatoid arthritis, etc.. Dr Kavanaugh points out that we have made a somewhat switch from “bench to bedside” to “bedside to bench.” He states that “we are dissecting these diseases by our therapies” with hopes to find more specific treatments for specific groups of patients with these distinct diseases.

Ustekinumab (USK) was approved for PsA in September of 2013. The PSUMMIT trial included 615 adult PsA patients with active disease despite DMARD and/or NSAID therapy. Patients were randomized to receive USK 45 mg, 90 mg, or placebo at weeks 0, 4, and q12 weeks thereafter. At week 16, patients with less than five percent improvement in tender joint count and swollen joint count entered blinded early escape (placebo to USK45 mg; USK 45 mg to 90 mg; 90 mg to 90 mg). Stable concomitant MTX use was permitted but not mandated. Patients treated with prior anti-TNF agents were excluded. The primary endpoint was an ACR20 response at week 24. A significantly greater proportion of USK-treated patients (versus placebo) had an ACR20 response at week 24. Significant improvements were also observed with USK 45mg and 90 mg for ACR50/70 responses and DAS28-CRP responses at week 24 versus placebo. Through week 16, adverse events were similar between patients receiving USK and placebo with infections being the most common AE. No malignancies, serious infections, tuberculosis, opportunistic infections, or deaths occurred through week 24. PASI 75 response at week 24 also demonstrated positive efficacy among the USK 45mg and 90mg doses versus placebo.

The PSUMMIT 2 study looked at USK in patients with active PsA who were previously treated with an anti-TNF agent. This data show some improvement in ACR 20/50/70 and demonstrate that it is safe and could be modestly effective for PsA TNF inhibitor-experienced patients.

Dr Kavanaugh and his colleagues, utilizing an integrated data analysis of two phase III randomized, placebo-controlled studies, also demonstrated that USK inhibits radiographic progression in patients with active PsA.

IL-17

Genovese, et al. studied brodalumab, an anti-IL-17RA in patients with PsA. ACR20 was achieved at week 12 by 37 percent and 39 percent of patients in the 140- and 280-mg brodalumab groups, respectively, compared with 18 percent of placebo patients. The percent of ACR20 responders (observed) increased at week 24 (44%, 51%, 64%, in prior placebo, prior 140 mg, and prior 280 mg groups, respectively). The percent of ACR50 responders (observed) across all groups increased from week 12 to week 24. There were improvements in other secondary endpoints such as DAS 28, CDAI, and several components of the ACR from baseline to week 12 that continued through week 24 in all treatment groups. Adverse events were similar among all treatment groups and placebo. This demonstrates that brodalumab is associated with significant clinical response with continued improvement from week 12 to 24 and further studies of brodalumab for treatment of PsA should be conducted.

Small Molecules

Apremilast, an inhibitor of PDE4, is currently under development for the treatment of PsA. Data from the PALACE 1 study are statistically significant for the apremilast group(s) versus placebo for both ACR 20/50/70 scores and PASI75. At week 24, significantly more apremilast 20 mg BID (36%) and 30 mg BID (45%) patients achieved ACR20 versus placebo (13%). There were also significant improvements in key secondary measures (physical function, psoriasis) with both apremilast doses versus placebo.

One of the major advantages of apremilast is its safety profile. Laboratory monitoring may not be needed with this drug.

Conclusions

Since the availability of biologics, the interest in PsA has increased exponentially. This is exciting for us, as healthcare providers, and very promising for our patients. Lastly, remember the importance of tight control in early PsA. If patients are not responding the way you feel that they should be, then their management strategy needs to be modified. Data demonstrate that using a treat-to-target approach can significantly improve both joint and skin outcomes for newly diagnosed PsA patients.

MauiDerm News Editor-Judy Seraphine

Actinic Keratoses: Clinical Pearls

March 10, 2014

George Martin, MD

Are you using 5-FU to treat AKs?

To minimize the duration of side effects, compliance issues and phone calls when prescribing 5-FU prescribe 0.5% 5-FU therapy for 1 week. Phase 3 FDA data on 0.5% 5-FU used for 1 week demonstrate over 70% individual lesion clearance. Is it worth continuing an extra 3 weeks to achieve a > 90% clearance? No.
What does Dr. George Martin do? He cycles 5-FU therapy: 1st cycle—Face: 7 days 5-FU/Non-facial areas: 10 days 5-FU; Rest period for at least one month; 2nd cycle— 5-FU for at least 2 weeks. Data suggest that 0.5% 5-FU QD is at least as effective as 5% 5-FU BID in percent reduction of AK lesions. The short treatment cycles result in great compliance and minimal downtime.

Treating AKs on the chest?

Avoid 3.75% imiquimod. It is likely to result in permanent depigmentation at the AKs treated sites on the chest in the majority of patients. It is not yet FDA approved for the trunk…and with good reason.
Try: ingenol mebutate 0.05% x 2 nights. Instead of spot treating, cover the entire sun-damaged AK area of the chest with the entire amount in the tube. Best used on moistened skin post shower because it spreads better. Because of its direct cytotoxic effect, in addition to up-regulation of IL-8 induced neutrophil chemotaxis, it produces discomfort within 4 hours requiring analgesia. Be sure to set patient expectations and prescribe analgesia. Patients describe it’s use on large areas on the upper chest as feeling like a “really bad sunburn.” Although not FDA approved to treat areas >25 cm2 and there is no efficacy data, Dr. Martin has found it to produce excellent AK clearance and a great cosmetic result.