Systemic Medications: Top Ten Take Home Points

Matthew J. Zirwas, MD 

  1. Prednisone is drug of choice for expected short term therapy – weeks.
  2. Cyclosporine is drug of choice for expected “medium term therapy” – months.
  3. Methotrexate is drug of choice for chronic therapy in patients without liver, kidney, or hematologic co-morbidities.
  4. Mycophenolate is drug of choice for chronic therapy in patients with liver, kidney, or hematologic co-morbidities.
  5. Cyclosporine has many drug interactions – must use a computerized drug interaction checker.
  6. Methotrexate has a few drug interactions but they are extremely serious and can be fatal.
  7. Mycophenolate has few drug interactions.
  8. Patients on methotrexate should take folic acid on days they do not take the methotrexate.
  9. Older patients on mycophenolate, in particular, are at high risk of zoster.
  10.  If patients on cyclosporine have elevations in creatinine, they need to stop the medication.

Pigmented Lesions: Clinical Pearls

Ashfaq Marghoob, MD

Dr Marghoob provides us with his clinical pearls on pigmented lesions….

  1. The larger the congenital nevus the greater is the risk for developing melanoma.
  2. The risk of a melanoma developing in a small congenital nevi is small enough that prophylactic excision is not required.
  3. Presence of many nevi and dysplastic nevi are strong risk factors for melanoma.
  4. Analytical, Differential and comparative recognition are all helpful in differentiating nevi from melanoma.
  5. Total body photography assists clinicians in finding concerning lesions.
  6. Dermoscopy assists clinicians in deciding which lesions require a biopsy.
  7. Unna’s theory of nevogenesis is not supported by recent cross sectional and longitudinal studies.
  8. Nevi with a peripheral globular pattern or a starburst pattern are growing nevi (not yet in senescence).
  9. Most halo nevi have a globular pattern.
  10. Patient driven healthcare with the use of Apps is likely to help in finding early melanomas.

Immunology 101: The Basics

Andrew Blauvelt, MD

Dr Blauvelt provides us with the 10 most important take-home messages from his immunology presentation at MauiDerm NP+PA Summer 2014….

  1. Key features of the innate immune system include: rapid response, non-specificity, phagocytosis, no memory.
  2. Key features of the  acquired immune system include: slow response, very specific, lymphocyte-mediated, memory.
  3. Keratinocytes are active participants in generating immune responses by secreting numerous cytokines upon activation.
  4. 4.Toll-like receptors are pattern recognition receptors on keratinocytes that recognize foreign antigenic material.
  5. Antimicrobial peptides are natural antibiotic molecules found in skin that are abundant in psoriasis skin and sparse in atopic dermatitis skin.
  6. 6.Epidermal Langerhans cells are antigen presenting cells that recognize/process skin antigens and migrate to lymph nodes, where they present antigen to T cells.
  7. 7.T cells require 3 signals to become fully activated: 1) recognition of antigen by the T cell receptor via MHC on the surface of antigen presenting cells; 2) binding of co-stimulatory molecules on T cells and antigen presenting cells to one another; and 3) secretion of soluble cytokines by the T cells.
  8. CD4+ T cells are T helper cells that recognize antigen via MHC class II and secrete cytokines to enhance CD8+ T cell and B cell immune responses, whereas CD8+ T cells are cytotoxic T cells that recognize antigen via MHC class I and kill cells upon contact.
  9. B cells secrete antibodies that specifically bind to antigen.
  10. Primary immune responses are slow, occur after first exposure to antigen, and involve creation of memory cells, whereas secondary immune responsesare fast, occur after subsequent exposures to antigens, and involve reactivation of memory cells.

 

 

Dermatitis Overview: 2014

Matthew J. Zirwas, MD

Are you treating dermatitis? Dr Zirwas provides us with ten clinical pearls…

  1. The main goal in dermatitis patients is figuring out WHY they have dermatitis.
  2. Acute allergic contact dermatitis starts 1-3 days after exposure to the allergen and takes 1-3 weeks to go away.
  3. Chronic allergic contact dermatitis takes 3-6 months to go away.
  4. Hypoallergenic rubber gloves are not hypoallergenic.  Hypoallergenic gloves include: vinyl gloves, Microtouch Nitra-Free, Dermaprene Ultra.
  5. Shampoo and conditioner are the main causes of eyelid dermatitis, both irritant and allergic.
  6. Atopic dermatitis is the combination of inadequate skin barrier and an immune system that was genetically primed to go in an allergic direction.
  7. Food avoidance and chelation do not work in adults.
  8. There are probiotics that work, but it is very specific – patients can’t just take any old probiotic.
  9. Seborrheic dermatitis is an inflammatory reaction to Malassezia yeast on the skin – treat by reducing amount of yeast and targeting the inflammation.
  10. Xerosis is too little water in the skin.  Need to add water and prevent it from just evaporating away.

 

Dermoscopy: Clinical Pearls

Ashfaq Marghoob, MD

Are you performing dermsocopy in your clinical practice? Dr Marghoob provides us with his clinical pearls…

  1. Dermoscopy helps in differentiating benign lesions from skin cancer.
  2. The presence of network (reticular network, negative network, polygonal lines), streaks (radial streaming, pseudopods), aggregated globules/peripheral globules, homogeneous blue pigmentation is most often seen in melanocytic lesions.
  3. Melanocytic lesions that deviate from the 10 benign patterns and has at least one of the 10 melanoma-specific structures needs to be biopsied to rule out melanoma.
  4. The presence of spoke wheel structures and/or leaf like areas is 100% specific for BCC.
  5. Comedo like openings and milia cyst are often seen in SK but can also be seen in other lesions including melanoma.
  6. Polarized light makes blood vessels and crystalline structures more conspicious, and makes milia cyst less conspicuous.
  7.  A polymorphous vascular pattern in an amelanotic lesion should raise concern for melanoma.
  8. Dermoscopy improves the clinician’s diagnostic accuracy.
  9. All structureless or featureless or not-otherwise-diagnosable lesions should be viewed with suspicion.
  10. Raised lesions should never be monitored for change.

Cutaneous Oncology: Talking Points

Marc Brown, MD

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

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

 

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

 

  1. 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.

 

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

 

  1. 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

Bruce Strober, MD, PhD

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

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

 

 

 

 

Pediatric Dermatology: Clinical Pearls

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

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:

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  • 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:

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  • 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

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:

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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)

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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