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Medical Dermatology

Aug 02
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CBD for Psoriasis?

By Medical Dermatology, Patient Care
CBD Oil for Psoriasis

Source: Next Steps in Dermatology

Health recently wrote an article asking if CBD oil can relieve psoriasis symptoms.

In recognition of Psoriasis Awareness Month, I consulted Adam Friedman, MD, FAAD, professor and interim chair of dermatology at the George Washington School of Medicine and Health Sciences. Dr. Friedman is also the residency program director, director of translational research and director of the Supportive Oncodermatology Clinic. In addition, Dr. Friedman serves as Medical Director for ODAC -Dermatology, Aesthetic & Surgical Conference.

Can CBD help relieve psoriasis symptoms? 

We have only begun to scratch the surface of the unbridled potential of cannabinoids as therapeutic agents. Interestingly enough, psoriasis is one of the listed indications for medical cannabis in the great state of Connecticut, though little is really known on this and many other spaces in dermatology.

Let’s take a step back and first talk about CBD. CBD stands for cannabidiol, one of about 120 different molecules that come from the cannabis plant. It’s the second most prevalent active ingredient in cannabis – tetrahydrocannabinol (THC) is the first. But unlike other cannabinoids – such as THC — CBD does not produce a euphoric “high” or psychoactive effect. That said, it has tremendous biological reactivity through binding to a multitude of receptors, including the cannabinoid specific receptor, CB2r, which is expressed by practically every immune cell (as opposed to CB1r, which is most heavily expressed in the peripheral and central nervous system), regulating skin physiology by being anti-inflammatory, lipostatic and antiproliferative.

Now back to the original question. Inflammatory skin conditions such as psoriasis result from a number of aberrant responses of the immune cells and immune signaling in the skin. Looking at psoriasis specifically, dysregulation of the skin immune system results in marked proliferation and keratinization of epidermal cells. Overactivation of Th1 and Th17 inflammatory responses in psoriasis produces cytokines like IL-17 and IL-22 that set off cascades of events resulting in increased keratinocyte proliferation, expression of keratins 6 and 16, and inflammatory cell infiltration. Because of its role in regulating the inflammatory response of keratinocytes and dermal immune cells, the endocannabinoid system offers potential targets for the management of many inflammatoryskin conditions, but the data to date is rather limited, mostly to cell bases, ex vivo and animal models.

This is what we know:Activation of the endocannabinoid system in the skin reduces inflammation through a number of mechanisms, such as shifting the pro-inflammatory Th1 response to an anti-inflammatory Th2 response via CB2r activation (thank you, CBD). The endocannabinoid system also plays a role in regulating keratinocyte proliferation and differentiation, which are pathologically increased in psoriasis. For example, CB1r activation by cannabinoids such as anandamide (AEA) inhibits keratinocyte differentiation and decreases production of keratin K6, a marker of keratinocyte hyperproliferation. The potential therapeutic effects of CBD in psoriasis also include activation of non-cannabinoid receptors such as GPR55, which reduces inflammation caused by nerve growth factor, and PPARα and PPARγ which reduces epidermal hyperplasia via suppressed proliferation of keratinocytes.

Jul 18
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What’s New in Itch

By Medical Dermatology, ODAC Sessions No Comments
ODAC Dermatology Conference faculty image

Dermatologists are well aware of the difficulty in managing itchy patients. Itch can be caused by a number of cutaneous and extracutaneous diseases. Regardless of the etiology, itch is one of the most frustrating symptoms of patients and management dilemmas for dermatologists. At the 16th Annual ODAC conference, Dr. Brian Berman reviewed some of the emerging therapies for the treatment of itch and the etiologies for which they are currently under investigation.

Nemolizumab is a monoclonal antibody directed at the IL-31 receptor A. It is currently being studied for use in atopic dermatitis. Recent phase II data have shown improvement for itch in atopic dermatitis over 64 weeks1. A few of the less common side effects that were seen in this study included peripheral edema and elevations in blood CPK levels.

Tapinarof cream is a first-in-class, naturally derived, non-steroidal topical agent. It is currently being investigated for use in psoriasis and atopic dermatitis. Tapinarof is a therapeutic aryl hydrocarbon modulating agent (or TAMA) and inhibits specific proinflammatory mediators, including IL-6 and IL-17A2.  One of the more interesting targets of tapinarof is nuclear factor-erythroid 2-related factor-2 (Nrf2), which happens to be one of the mechanisms through which coal tar produces its beneficial effects.

Hypochlorous acid gel is being used for its anti-inflammatory properties. This topical has potential utility for atopic and seborrheic dermatitis-related itch.

Serlopitant is an oral NK1 receptor antagonist. It is currently being investigated for use in chronic pruritus, pruritus in psoriasis, and prurigo nodularis. Substance P binds to the NK1 receptor peripherally, in the ganglion and brain to cause/increase the perception of itch, and as such, NK1 receptor antagonists are an up and coming mechanistic target for itch. Phase II data appear to be promising3.

Remetinostat (previously referred to as SHAPE), a topical histone deacetylase inhibitor, is currently under investigation for treating pruritus in patients with stage IA-IIA mycosis fungoides4. Preliminary data are promising as the topical route of the medication appears to decrease itch while limiting side effects compared to systemic histone deacetylase inhibitors.

Omalizumab, an anti-IgE monoclonal antibody, is approved for use for chronic idiopathic or chronic spontaneous urticaria5. It is notable that in the pivotal, phase 3 study published in the New England Journal of Medicine, the primary endpoint was itch-severity score rather than urticarial lesion counts. The use of this endpoint highlights the magnitude of itch in urticaria.

Read More…

Jul 10
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What’s New for Itch

By Medical Dermatology, ODAC Sessions
ODAC Dermatology Conference Dr. Berman Image

Source: Next Steps in Dermatology

Dermatologists are well aware of the difficulty in managing itchy patients. Itch can be caused by a number of cutaneous and extracutaneous diseases. Regardless of the etiology, itch is one of the most frustrating symptoms of patients and management dilemmas for dermatologists. At the 16th Annual ODAC conference, Dr. Brian Berman reviewed some of the emerging therapies for the treatment of itch and the etiologies for which they are currently under investigation.

Nemolizumab is a monoclonal antibody directed at the IL-31 receptor A. It is currently being studied for use in atopic dermatitis. Recent phase II data have shown improvement for itch in atopic dermatitis over 64 weeks1. A few of the less common side effects that were seen in this study included peripheral edema and elevations in blood CPK levels.

Tapinarof cream is a first-in-class, naturally derived, non-steroidal topical agent. It is currently being investigated for use in psoriasis and atopic dermatitis. Tapinarof is a therapeutic aryl hydrocarbon modulating agent (or TAMA) and inhibits specific proinflammatory mediators, including IL-6 and IL-17A2.  One of the more interesting targets of tapinarof is nuclear factor-erythroid 2-related factor-2 (Nrf2), which happens to be one of the mechanisms through which coal tar produces its beneficial effects.

Hypochlorous acid gel is being used for its anti-inflammatory properties. This topical has potential utility for atopic and seborrheic dermatitis-related itch.

Serlopitant is an oral NK1 receptor antagonist. It is currently being investigated for use in chronic pruritus, pruritus in psoriasis, and prurigo nodularis. Substance P binds to the NK1 receptor peripherally, in the ganglion and brain to cause/increase the perception of itch, and as such, NK1 receptor antagonists are an up and coming mechanistic target for itch. Phase II data appear to be promising3.

Remetinostat (previously referred to as SHAPE), a topical histone deacetylase inhibitor, is currently under investigation for treating pruritus in patients with stage IA-IIA mycosis fungoides4. Preliminary data are promising as the topical route of the medication appears to decrease itch while limiting side effects compared to systemic histone deacetylase inhibitors.

Omalizumab, an anti-IgE monoclonal antibody, is approved for use for chronic idiopathic or chronic spontaneous urticaria5. It is notable that in the pivotal, phase 3 study published in the New England Journal of Medicine, the primary endpoint was itch-severity score rather than urticarial lesion counts. The use of this endpoint highlights the magnitude of itch in urticaria.

Physician assurance reduces itch. In a recent study6, a physician administered a histamine skin prick to 76 participants. After 3 minutes, half of the randomly selected participants were assured by the physician in the following way. “From this point forward your allergic reaction will start to diminish, and your rash and irritation will go away.” In the assured group, it was found that over the next 15 minutes, itchiness of the area declined significantly faster than the group not assured by the physician.

Read More…..

May 30
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Sentinel Lymph Node Biopsy for Melanoma

By Medical Dermatology, ODAC Sessions, Surgical Dermatology
Dr. Zitelli Presenting at ODAC

Source: Next Steps in Derm

Backed by a mountain of evidence, Dr. Zitelli walked us through the new and changing role of sentinel lymph node biopsy for melanoma in a riveting 20-minute talk presented at the 16th annual ODAC conference. Here are the highlights.

“Let’s separate what’s really evidence based from what you’ve been told.”

Before delving in, Dr. Zitelli skillfully laid the framework for his lecture. The crux of sentinel lymph node biopsy is based on the theory of orderly progression, in which malignant melanoma cells leave the tumor and preferentially enter the lymphatics and the first lymph node. This theory is rivaled by the anatomic pathway, in which malignant melanoma cells may enter the lymphatics or  the blood stream, resulting in simultaneous dissemination.

Which theory is correct?

The overwhelming preponderance of evidence supports the latter anatomic theory – melanoma cells may enter the blood stream directly or the lymphatics, potentially bypassing the sentinel node. This anatomic theory is evidence based. It refutes the theory of orderly progression that the concept of sentinel lymph node biopsy is based on. Another common misconception is that lymph nodes are filters – they are not. Lymph nodes are sampling organs, sampling antigens in order to initiate an immune response.

With the groundwork laid, Dr. Zitelli went on to summarize the emerging evidence for sentinel lymph node biopsy. “This is what you need to know when you counsel a patient in order to obtain true informed consent.”

What you’ve been told: Sentinel lymph node biopsy improves survival
What the evidence shows: There is not a single solid tumor for which sentinel lymph node biopsy has been shown to provide a survival benefit.

We’ve been told that sentinel lymph node biopsy improves survival in intermediate thickness melanoma, because subclinical deposits are removed from the lymph nodes before they can grow. In fact, 33% of patients who underwent sentinel lymph node biopsy, did so because they thought it would improve their survival. Yet, there is not a single solid tumor – melanoma, gastric, renal, thyroid or otherwise – where electively removing normal lymph nodes, even in the case of microscopic involvement, has shown a survival benefit.

A cornerstone trial, the Multicenter Selective Lymphadenectomy Trial (MSLT-1), set out to prove the survival benefit of sentinel lymph node biopsy in melanoma. However, sentinel lymph node biopsy failed to improve melanoma specific survival. Subsequently, MSLT-2 looked at whether removing positive lymph nodes further down the line would improve survival in patients who had positive sentinel lymph nodes – this was also a negative study.

Read more. 

May 11
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SLNB for Melanoma

By Medical Dermatology, ODAC Sessions, Surgical Dermatology
Melanoma on Patient

Source: Dermatology Times

Sentinel lymph node biopsy (SLNB) has classically been performed for regional disease control and to hopefully prevent disease metastasis; however, according to one expert, there has not been any good evidence to support this practice. As such, it is important for clinicians to focus on the evidence when planning the treatment and management of their advanced melanoma patients.

“Over the last decade or so, the role of SLNB has been changing, and there is no real consensus as to when to perform the procedure because it is a very rapidly changing field. The touted usefulness in survival benefit or prognosis of SLNB simply cannot be backed up by the available data, essentially rendering the appropriate use of SLNB in therapeutic limbo,” said John Zitelli, M.D., clinical associate professor, departments of dermatology & otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Penn., who spoke at the Orlando Dermatology and Aesthetic Conference.

According to Dr. Zitelli, the theory that SLNB would provide a survival benefit was debunked with the MSLT-1 research study1 recently published in the New England Journal of Medicine, and the idea that the procedure was to be considered as the most accurate prognostic test was also shown to be untrue. There usually is no need to do a SLNB, Dr. Zitelli said. The Breslow thickness, as well as all of the presenting clinical pathological morphologic features, such as ulceration of the tumor, is a wealth of information that the clinician can use to contemplate appropriate further treatment and management of the patient. Many clinicians still prefer to perform SLNB, Dr. Zitelli said, reasoning that waiting until the tumor is palpable would likely be synonymous with greater complications.

“The premise is off, because if you’re performing SLNB on a lot of people and the complication rate is low but the number of patients who are getting the procedure is high, the long-term complication rate in a group of people who you manage with SLNB actually have more complications than the smaller group of patients who have a complete node dissection from palpable disease,” Dr. Zitelli said.

Controversy revolving around the role of SLNB and its true usefulness in melanoma therapy and management continues today. The current contemporary wisdom is that SLNB should be performed because the results could help determine which patients would be more amenable to adjuvant therapy.

Read More….

May 01
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Hyperhydrosis: Where are we?

By Medical Dermatology, ODAC Sessions
Hydrosis Chart

Source: Next Steps in Derm

Can you think of a skin condition that has a greater negative impact on quality of life than eczema or psoriasis?  That’s right, you guess it—hyperhidrosis!  I still remember my first hyperhidrosis patient who refused to shake people’s hands, go on dates, or attend social events due to his condition.  After his treatment, he was like a new man.  I can’t tell you how satisfying it was to see his life changed after treatment. That’s why I’m so excited to share what I learned from Dr. Adam Friedman at ODAC 2019 regarding hyperhidrosis.   Dr. Adam Friedman is Professor and Interim Chair of Dermatology, Residency Program Director, Director of Translational Research, and Director of the Supportive Oncodermatology Clinic in the Department of Dermatology at The George Washington University School of Medicine & Health Sciences.

Did You Know?

Nearly 5% of the world’s population suffers from hyperhidrosis—that’s 365 million people worldwide! In the U.S., 7.8 to 13.4 million people (2.8-4.8%) are estimated to be affected by hyperhidrosis—that’s comparable to the prevalence of psoriasis.  Spalding et al. showed that patients with hyperhidrosis reported a worse quality of life compared to those with atopic dermatitis or psoriasis (Value in Health 2003).  That made me raise my eyebrows for sure!

Hyperhidrosis stats
Spalding et al. Value in Health 2003;6(3):242(abstract)

 

Know Your Sweaters: First, Diagnose

Hyperhidrosis can be divided into primary (usually focal) and secondary (generalized).  For secondary hyperhidrosis, the underlying cause needs to be addressed, which may include drugs, cardiovascular disorders, respiratory failure, infections, malignancies, and metabolic disorders.  For primary hyperhidrosis, now, that’s where we dermatologists step in and save the day. So, what are our options?

Treatment Options

There are non-invasive, minimally invasive, and surgical options for the treatment of hyperhidrosis.  Here, we will discuss everything but surgical options and energy-based treatment.

  • Topical aluminum chloride, aluminum chloride hexahydrate, or aluminum zirconium trichlorohydrex
    • This is applied on skin overnight (to remain on skin for 6-8 hours, during non-sweating hours) and washed off in the morning before sweating begins
    • A non-medicated deodorant should be applied in the morning after showering
    • Can use topical steroids for skin irritation
    • Cons: itching and burning of skin, time-consuming, can damage fabrics, temporary relief
  • Inotophoresis
    • Need treatment for 20-30 minutes a session, 3-4 times a week. This can be effective (81-91% response), but who has time for that?
    • Cons: cumbersome, can be costly, long-term therapy, and again…time-consuming
  • Topical glycopyrronium tosylate (Qbrexa)—the new kid on the block! And he’s FDA-approved, too. Whoohoo!
    • This can be applied nightly onto clean skin and can be used in conjunction with an over-the-counter antiperspirant
    • Improvement can be expected in 1-3 weeks.
    • Can be used in kids (approved for >9 years of age)
    • Cons: anticholinergic side effects such as dry eyes, dry mouth, blurred vision (need to emphasize the need to wash hands thoroughly after use to minimize risk), long-term therapy, may be costly
  • Systemic anticholinergics: off-label use for hyperhidrosis
    • Glycopyrrolate
      • Can start at 1mg twice daily and increase up to 6mg a day, or until limited by anticholinergic side effects
    • Oxybutynin
      • Can start at 5 to 10mg daily and increase to 15 to 20mg daily
      • A study in kids showed a 90% response rate at 2mg daily.
    • Cons: again, anticholinergic side effects — ones listed above, as well as constipation, urinary retention, bradycardia, etc.
  • Beta-adrenergic blockers
    • This is great for patients with social phobias and performance anxiety!
    • Most can tolerate a dose of 10 to 20mg (to be taken 1 hour before). But don’t forget to check the resting blood pressure and heart rate beforehand!  Oh, and also, they need a “test run” at home, just to make sure all goes smoothly before the actual “showtime”.
    • Contraindications: bradycardia, AV block, asthma
  • Botulinum toxin injection
    • Before treatment: patients should avoid deodorants for 24 hours prior and rest comfortably for 30 minutes prior
    • Treatment: after making an outline of the area, inject at a depth of 2mm, at a 45 degree angle with the bevel up, 1-2cm apart
    • What to expect: onset is about 2-4 days and duration is 3-7 months
    • Other considerations
      • Topical analgesics help a ton!
      • Do not use sterile water—can sting
      • If you buy the toxin and inject, use the CPT code 64650 and J code J0585 (with units)
      • If you prescribe the toxin to a pharmacy, provider bills only for the injection service, and patient pays co-pay for both the toxin and injections
    • Cons: can be painful and expensive

Read More…

Apr 25
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Pathophysiology and Management of Rosacea

By Medical Dermatology, ODAC Sessions
Dermatology Patient with Rosacea

Source: Next Steps in Derm

This information was presented by Dr. Adam Friedman at the 16th Annual ODAC Dermatology, Aesthetics and Surgical Conference held January 18th-21st, 2019 in Orlando, FL. The  highlights from his lecture were written and compiled by Dr. InYoung Kim.

If you’re a coffee drinker, you may be relieved to know that there was an inverse association between caffeine intake and risk of rosacea in a recent study.  That was a huge relief for me for sure! Unfortunately, we can’t prescribe caffeine for rosacea and call it a day. So, what works?

High-yield pearls on the pathophysiology and management of rosacea are shared by Dr. Adam Friedman – Professor and Interim Chair of Dermatology, Residency Program Director, Director of Translational Research, and Director of the Supportive Oncodermatology Clinic in the Department of Dermatology at The George Washington University School of Medicine & Health Sciences. Here are the highlights.

New Approach to Diagnosis and Categorization of Rosacea

First, let’s talk about diagnosis.  Rather than categorizing into 4 classic subtypes that we learned in the textbook, rosacea may be better defined by “phenotypes”.  Diagnostic phenotypes include 1) having fixed centrofacial erythema in a characteristic pattern that may periodically intensify or 2) phymatous changes.  In the absence of these, the presence of 2 or more major features may be diagnostic, including papules/pustules, flushing, telangiectasia, ocular symptoms.  Some secondary phenotypes that may help with diagnosis are burning/stinging, edema, dry appearance, and ocular rosacea.

Rosacea in Skin of Color – Rosacea Does Not Discriminate!

While rosacea has widely been considered a disorder selectively affecting the Caucasian population, this is not true! Perhaps due to this bias, delayed diagnosis has been reported in substantial numbers.  In fact, the prevalence of rosacea in skin of color is as high as 10%!  That is significant.  Please spread the word!  So how do they present differently than Caucasian patients? While you may not see the persistent facial erythema (which is common in whites), the granulomatous subtype and papules/pustules are more common in skin of color.  Asking about the secondary phenotypes noted above (burning/stinging, edema, dry appearance, and ocular rosacea) may also be helpful in diagnosis.

Therapeutic Options – Combo is King!

While many prescription treatment options exist (outlined below), patient education concerning proper general skin care is of utmost importance.  Make sure to include these in your counseling: daily sunscreen, gentle moisturizers, gentle cleansers, avoid triggers.

A list of FDA-approved topical therapies that you may choose from:

  • Azelaic acid (15% gel/foam)
  • Metronidazole (0.75% and 1%)
  • Sodium sulfacetamide 10% and sulfur 5%
  • Brimonidine (0.33% gel)
  • Ivermectin 1%
  • Oxymetazoline (1% cream)

What would a typical daily plan look like for a moderate-to-severe rosacea patient?  Here are Dr. Friedman’s tips:

Read More….

Apr 12
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Dr. Jean Bolognia’s Approach to Atypical Nevi

By Medical Dermatology, ODAC Sessions
Atypical Nevi on Patient leg

Source: Next Steps in Derm

This information was presented by Dr. Jean Bolognia at the 16th Annual ODAC Dermatology, Aesthetics and Surgical Conference held January 18th-21st, 2019 in Orlando, FL.  The highlights from her lecture were written and compiled by Dr. Daniel Yanes.

Despite being one of the more common reasons for consulting a dermatologist, the diagnosis and management of atypical nevi remain nuanced and can often be challenging. I had the opportunity to learn from Dr. Jean Bolognia on her approach to atypical nevi, and walked away with many pearls to share.

1. Identify the patient’s signature nevus and come up with a plan.

Sometimes it can be overwhelming to know where to begin when tasked with the patient who has numerous and atypical nevi. The first step is to identify the patient’s signature nevus. Do they tend to grow fried egg nevi, eclipse nevi, or cockade nevi? Are their signature moles all pink with little brown pigment, or are they pitch black with a wafer of scale? Identifying the signature nevus assists in determining the ugly duckling, and it will also help you develop a practical approach. In addition, if the patient has primarily pink nevi, palpation for induration versus soft flabbiness is helpful as banal intradermal melanocytic nevi can be pink in color.  If the patient has primarily small flat black nevi, you should hone in on the presence of inflammation that is not simply due to acne or folliculitis. Creating an individualized plan is the key to a successful examination.

2. Nevi change, and sometimes it is simply an aging phenomenon.

In addition to identifying the signature nevus, it is also essential to understand how melanocytic nevi evolve over time. While nevi classically progress from junctional to compound and then to dermal, sometimes they simply fade away. In the case of fried egg nevi, the “yolk” becomes more raised and softer over time while the “white” of the egg gradually fades (figure 1). This results in multiple large dermal nevi on the trunk in an older patient. Patients can be taught that when a nevus elevates, determining if the lesion is firm versus soft can assist in distinguishing between the need for evaluation versus an aging phenomenon. Although not all changing nevi are concerning nevi, it is still essential to give the patient’s nevus of concern special attention, even if it doesn’t catch your eye at first.

Continue reading. 

Apr 04
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Systemic Therapies for Melanoma: What Every Dermatologist Needs to Know

By Medical Dermatology, ODAC Sessions
List of current melanoma therapies

Source: Next Steps in Derm

This information was presented by Dr. Jean Bolognia at the 16th Annual ODAC Dermatology, Aesthetics and Surgical Conference held January 18th-21st, 2019 in Orlando, FL.  The highlights from her lecture were written and compiled by Dr. Daniel Yanes, one of the 5 residents selected to participate in the Sun Resident Career Mentorship Program (a program supported by an educational grant from Sun Pharmaceutical Industries, Inc.). Dr. Yanes was paired with Dr. Jean Bolognia as his mentor.  

The world of melanoma is evolving, and dermatologists need to be equipped with the knowledge to help their patients navigate this landscape. Newer therapies for patients with more advanced stages of melanoma have not only drastically improved survival, but we as dermatologists must be prepared to recognize and treat the cutaneous side effects of these medications. This is a brief summary of common systemic therapies for melanoma with which every dermatologist should become familiar.

MAP Kinase Pathway Inhibitors

Selective BRAF Inhibitors

Melanoma tumor cells often have activating mutations that lead to constitutive activation of the MAP kinase pathway (See figure). Such activation can then lead to unregulated cell growth and proliferation. The most commonly detected mutation in BRAF results in the substitution of glutamic acid (E) for valine (V) at the 600th position in the BRAF protein and is referred to as BRAF V600E. Selective BRAF inhibitors, e.g. dabrafenib, encorafenib and vemurafenib, specifically target altered BRAF proteins. You can easily recognize these medications from their names, with raf indicating they target (B)RAF and nib identifying them as inhibitors. They are administered orally and chronically and lead to rapid responses but unfortunately tumor resistance commonly develops, often within six months. There are cutaneous side effects that the dermatologist should recognize, including morbilliform and folliculocentric eruptions, UVA photosensitivity (e.g. vemurafenib), keratoacanthomas/squamous cell carcinomas, and changes in melanocytic nevi (eruptive, enlargement, involution).

MEK Inhibitors

When mechanisms of resistance to selective BRAF inhibitors were investigated, a common finding was re-activation of the MAP kinase pathway via activation of MEK, another kinase that is downstream from BRAF. MEK inhibitors, e.g. binimetinib, cobimetinib, trametinib, were then combined with selective BRAF inhibitors to reduce the development of tumor resistance. These drugs are identified by the presence of a -metinib suffix. Interestingly, compared to BRAF inhibitors alone, combination BRAF+MEK therapy is associated with significantly less, not additive, cutaneous side effects – a real benefit to the patient.

Immunotherapy – Checkpoint Inhibitors

Immunotherapy is designed to stimulate the immune system to attack immunogenic melanoma cells. These monoclonal antibodies inhibit inhibitory signals that normally downregulate the immune system and thus act as immune checkpoints. These drugs model after the saying “the enemy of my enemy is my friend,” only it’s now “the inhibitor of the immune inhibitor is the immune stimulator.” CTLA4 is a receptor on regulatory T cells that plays an important role in diminishing immune responses. By blocking the inhibitory function of CTLA4 during the priming phase, the anti-CTLA4 antibody ipilimumab increases T cell immune activity. Peripherally, when the PD-1 receptor on T cells binds to its ligand, PD-L1, on tumor cells, an inhibitory signal results. In a similar fashion, the anti-PD-1 monoclonal antibodies approved for melanoma – nivolumab and pembrolizumab – can increase anti-tumor immune activity. Anti-PD-L1 monoclonal antibodies (e.g. avelumab, atezolizumab, durvalumab) have been approved to treat other malignancies, including Merkel cell carcinoma.

Read more. 

Mar 30
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Dr. Jean Bolognia and the Many Faces of Lupus

By Medical Dermatology, ODAC Sessions
Dr. Jean Bolognia presenting at ODAC Dermatology Conference

Source: Next Steps in Derm

This information was presented by Dr. Jean Bolognia at the 16th Annual ODAC Dermatology, Aesthetics and Surgical Conference held January 18th-21st, 2019 in Orlando, FL.  The highlights from her lecture were written and compiled by Dr. Daniel Yanes.

Just as systemic lupus erythematosus (LE) can have protean systemic manifestations, cutaneous LE can present in many different ways. When confronted with the many faces of mucocutaneous LE, the following pearls can be valuable.

1. Be Aware of the SLICC Criteria

In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) developed a set of clinical and immunologic criteria to assist in the diagnosis of systemic LE.

To view the original image full size image, click here.

To meet criteria for systemic LE, a patient must fulfill at least four criteria, with at least one clinical criterion and one immunological criterion OR have biopsy-proven lupus nephritis in the presence of ANA or anti-dsDNA antibodies. Of the 11 clinical criteria, 4 are mucocutaneous: (1) acute or subacute cutaneous LE; (2) chronic cutaneous lupus; (3) non-scarring alopecia; and (4) oral or nasal ulcers. Of note, the dermatologist doesn’t just establish the diagnosis of cutaneous LE, but can also determine the specific types of autoantibodies the patient is forming as well as if the patient has systemic involvement (e.g. hematologic or renal abnormalities). Remember the latter requires a urinalysis in addition to bloodwork. Acute cutaneous LE is more closely associated with systemic LE than subacute cutaneous LE, which in turn is more closely associated with systemic LE than discoid LE. The cutaneous manifestations of LE per the SLICC classification scheme are as follows:

Acute cutaneous lupus

  • Lupus malar rash (does not count if malar discoid)
  • Bullous eruption of systemic LE
  • Toxic epidermal necrolysis variant of systemic LE [also sometimes referred to as acute syndrome of apoptotic pan-epidermolysis (ASAP)]
  • Maculopapular lupus rash
  • Photosensitive lupus rash in the absence of dermatomyositis

Subacute cutaneous lupus

Chronic cutaneous lupus

  • Classic discoid LE
  • localized (above the neck)
  • disseminated (above and below the neck)
  • Hypertrophic (verrucous) LE
  • Mucosal LE
  • Lupus panniculitis (profundus)
  • LE tumidus
  • Chilblain lupus
  • Discoid LE/lichen planus overlap

2. A Positive ANA Does Not Equate to Systemic LE.

While ANA titer is positive in nearly all patients with systemic LE, not all patients with a positive ANA titer have LE.

Continue reading. 

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