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Dermbits

Why has the 40-GEP test been validated on several data sets?

When starting a patient on an oral beta blocker for rosacea, how do you counsel them about side effects?

You. So when using the oral beta blockers for flushing associated with rosacea, you do want to counsel patients. The top side effects that can be experienced with the beta blockers are side effects related to hypotension and bradycardia. Some patients do develop fatigue, which is one of the more common side effects on the beta blockers. You do, like I said, counsel about hypotension, bradycardia, possibly dizziness, which could be associated with those symptoms. It's best always to start at a lower dose and gradually titrate upwards as the patient tolerates it until you see a response.

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What are high risk features of cSCC?

What are high risk features for cutaneous squamous cell? Well, it really depends upon who you ask. There's, of course, the four from Brigham and women's is it large? Is it down to the fat? Is there perineural invasion, or is it poorly differentiated? But there's other important ones, such as immunosuppression, that they seem to have forgotten. That matters to me. And then also think about other pathologic features as well as clinical features, such as it's growing quite fast, or I care about whether or not there's nerve involvement. It's not always easy to find perineural invasion, but if you tap in the area and they're having some sort of sensation, then you know that guess what? The nerve is likely to be involved as well. So there are lots of high risk features. Years and years of experience really help us identify which features matter for us and for each patient. And.

What is the best sunscreen to prevent skin cancer?

I love questions about sunscreen because I did one of the FDA studies along with Dr. Regal looking at high SPF sunscreen. And really, my advice for the best sunscreen is something that is a well known name brand because those companies, those products go through much more rigorous testing. And then I also encourage my patients to use the highest SPF possible, because in that study, what we found is you were ten times more likely to get a sunburn on an SPF split face study on the SPF 50 side than you were with SPF 100. The reality is our patients, the general public, they don't apply enough sunscreen, and they often don't reapply so that higher SPF provides a greater level of safety. But at the end of the day, the best sunscreen is the one that you're going to actually use. It.

Join leading dermatology experts as they review the Risk Evaluation and Mitigation Strategy (REMS) program for plaque psoriasis! Click <a target="_blank" rel="noopener noreferrer" href="https://google.com">here</a>

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The REMS Process for Psoriasis

Navigating Patient Conversations

The following are opinions of Dr. Tina Bhutani and are not intended to replace the informed consent process between a doctor and patient, nor is it intended to serve as medical and or legal advice. This video is not intended to replace all of the REMS requirements. More information will be discussed later in this video. Hello, I'm Tina Bhutani, the co director of the UCSF Psoriasis and Skin Treatment center and the UCSF Dermatology Clinical Research unit director. I work at a tertiary referral center at a university, so patients come to me after they have tried and failed biologics. I rarely see patients who are biologic naive for the adult patient who has tough to treat psoriasis and has already tried one, two, now even sometimes three biologics. By the time they come into my office, I think about Siliq I am a certified Siliq prescriber. I'm here today to talk to you about an important conversation you should have about suicidal ideation and behavior with patients you're considering prescribing Siliq for, and to take the mystery out of that worthwhile and simple conversation. Siliq is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond to or have lost response to other systemic therapies. Patients who come to me with tough to treat psoriasis have usually failed other biologics and don't really think there's much hope of finding a treatment that may work for them and that can really take a toll on them. We know that unfortunately, patients with psoriasis are more likely to be diagnosed with mental health disorders such as depression and anxiety, so we should be talking to them about this. I bring this up because to put patients on Siliq, you have to follow the Siliq risk evaluation and mitigation strategy, or REMS program. The reason for this is during the clinical trials for Siliq, there were some patients who had suicidal thoughts and unfortunately, a few who also died by suicide. While we don't think this is unique to Siliq, it's important to inform your patients about it. And remember, patients with a history of depression can still use siliq as long as their depression is controlled. However, there is a boxed warning for suicidal ideation behavior. Today I will cover how I discuss important safety information about Siliq, including the boxed warning and the REMS program with my patients who are first starting Siliq. My REMS conversation is fairly easy and it typically takes about three minutes I start off with what to expect in terms of efficacy and safety, and then tell them you're going to notice there's a warning about suicidal ideation and behavior. We know that patients with psoriasis are more likely to be diagnosed with depression. In line with that during the clinical trials. Sadly, four patients out of 4400 committed suicide because of this warning. We're going to talk about it today and go through some paperwork and have you sign off on the REMS program. I'll pull out the paper form from the drawer and walk through the form step by step. The forms are quick and easy. I will talk about suicidal ideation and behavior and the fact that it's a comorbidity of psoriasis. I explained to them, I want you to be very aware of your mood, and should you notice any new or worsening depression or any depressed thoughts whatsoever, or if you have any thoughts of hurting yourself, I want you to get in touch with me as quickly as possible. If you can't get in touch with me, we're going to give you this card that has the phone number for the National Suicide Prevention hotline. I want you to keep this card in your wallet at all times, and I want you to call this number and seek immediate attention should you have any issues while you're taking this drug. I also want you to ask people around you to let you know if they notice you're becoming depressed, because sometimes you're not aware of your mood changes, but others around you might be. At the end of the discussion, the patient signs the form, and my office staff will fax it. And that's really it. That's how I make sure I'm following the sale REMS program requirement. The paper forms for us are quick and easy. While I typically stick to the paper process, the electronic component is available and does a good job. Electronic forms would save my office the time of faxing in the form. Even though it doesn't take that long, some REMS programs can seem very burdensome and time consuming. The Siliq REMS program is not like this. It's super quick and easy to not only register yourself as a rems provider, but also to get your patients signed up for the first time, you prescribe siliq. When patients come to me, they're tired and have seen a ton of doctors. They don't really think anything will help them, but they still want to talk about it. I've had so many of these patients put on Siliq, and they're responding, which is a great thing. We know that areas like the scalp, the palms, and the soles are tougher to treat. I've had great experiences using siliq with many patients in the past. There's a case of two brothers with terrible, tough to treat psoriasis. They had tried and failed cyclosporin, methotrexate, and all the biologics. We put them on Siliq and they responded. Even today, they're still clear. Generally, by the three month point, we see a lot of clinical improvement for these patients. Solique has helped so many of my patients, and having these brief rems conversations saves a lot of time in the long run. You're documenting exactly the conversation that you're having, and it has the patient's signature right there on it. A REMS program ensures that the patient and the doctor have a full conversation versus when we're prescribing many other biologics, it is important to talk about it in our practice. We should be encouraging these types of conversations because for our patients, having psoriasis can be tough as it is now. Before we close, I want to be sure you get a chance to hear some additional information about the Siliq REMS program and important safety information for SiLIQ. The Siliq REMS program physicians must register for the Siliq REmS program@salerems.com. Discontinuation or transfer of care must be reported to the Siliq REMS program. This video is not intended to replace all of the REMS requirements. Complete details about the SiLIQ rems are available@salikrems.com. Indication SilIQ injection is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Important safety information warning suicidal ideation and behavior suicidal ideation and behavior, including completed suicides, have occurred in patients treated with Siliq. Prior to prescribing SilIq, weigh the potential risks and benefits in patients with a history of depression and or suicidal ideation or behavior. Patients with new or worsening suicidal ideation and behavior should be referred to a mental health professional as appropriate. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior, new onset or worsening depression, anxiety, or other mood changes. See warnings and precautions in the full prescribing information. Because of the observed suicidal behavior in subjects treated with SiLIQ, SiLIQ is available only through a restricted program under a risk evaluation and mitigation strategy rems, called the Siliq REMS program. See warnings and precautions in the full prescribing information. Crohn's disease Siliq is contraindicated in patients with Crohn's disease. In clinical trials, which excluded Crohn's patients, one Siliq patient was withdrawn after developing Crohn's disease. Discontinue Siliq if a patient develops Crohn's disease. Siliq risk evaluation and mitigation strategy REMS program Siliq is available only through a restricted program called the sale rems because of observed suicidal ideation and behavior in patients treated with Siliq. Before prescribing Siliq, prescribers must be certified with the program. Have each patient sign a patient prescriber agreement form and provide the patient a wallet card describing symptoms requiring immediate medical evaluation. Pharmacies must be certified and only dispensed to patients authorized to receive SiLIQ. More information is available@saliquerems.com or by calling the Salik REMS program call center at 855-11-6135 infections SiLIQ may increase the risk of infections serious infections and fungal infections were observed at a higher rate in patients treated with SiLIQ than placebotreated patients in clinical trials, including one case of cryptococcal meningitis that led to discontinuation of therapy. Consider risks and benefits prior to prescribing SiLIQ in patients with a chronic infection or history of recurrent infection. Instruct patients to seek treatment if signs or symptoms of a chronic or acute infection occur. Risk for latent tuberculosis TB reactivation evaluate patients for TB prior to initiating treatment with SiliQ and do not treat patients with active TB. Initiate treatment for latent TB prior to starting SilIQ and consider anti TB therapy prior to initiation in patients with history of latent TB if adequate treatment cannot be confirmed. Monitor closely for symptoms of active TB during and after treatment immunizations avoid use of live vaccines in patients treated with Siliq. Adverse reactions the most commonly reported adverse reactions in clinical trials were arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions, influenza, neutropenia, and tinia infections. To report suspected adverse reactions, contact Bauch Health at 1803 214576 or the FDA at 1800 FDA 1088 or visit FDA Gov medwatch. Please see full prescribing information, including boxed warning about suicidal ideation and behavior@salique.com.

Watch as Tina Bhutani, MD, explains how she discusses an important topic with her patients being treated for moderate-to-severe plaque psoriasis who participate in the REMS program. Dr. Bhutani describes how she structures the patient conversation about the program, the importance of discussing the mental health comorbidities of psoriasis, and how she advises patients on what to do if they notice changes in mood or symptoms of depression. She also describes the simple process of navigating and submitting the REMS program forms.

Important and Easy Conversations

The following are opinions of Dr. Scott Drew and are not intended to replace the informed consent process between a doctor and patient, nor is it intended to serve as medical and or legal advice. This video is not intended to replace all of the REMS requirements. More information will be discussed later in this video. Hi there. I'm Dr. Scott Drew, a medical and surgical dermatologist at Dermatology Associates of mid Ohio. I've been practicing dermatology for over 30 years, and I've been using SiLIQ extensively since it was approved in 2017. I'd like to share with you my approach to discussing Siliq with my patients, and in particular the Siliq Risk Evaluation and mitigation strategy, or REMS program. This video will cover the Siliq boxed warning and other important safety information. Siliq is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Let me start by saying I choose siliq because it has a unique mechanism of action. It acts as a cell membrane and binds to the IL 17 receptor, so it blocks the whole IL 17 family, not just the IL 17 a homodimers, but also the IL 17 af heterodymers. It's an important drug for many of my adult patients with psoriasis. We have a unique practice in that we're often a referral center for psoriasis. Some patients who come to us have had Pasi 20 or 30 or 40 on other systemic treatments or light therapy, including other biologics. This is when we think about Celik. But to use SilIQ, patients have to enroll in the REMS program. As dermatologists, we are familiar with this sort of program, especially for patients with serious skin diseases and the kind of treatments that we use. We do it for those products. We need to do it for Salik, too. And the reason for the Salik REMS program is that, sadly, there were four suicides in the phase three trials for Salik out of over 4400 patients. For this reason, Salik has a box warning in the full prescribing information. So we need to disclose that suicidal ideation and behavior, including completed suicides, have occurred in patients treated with Siliq in the clinical trials. The REMS program helps ensure that we, patients and doctors, both keep this in mind and detect and deal with any concerns that arise. And I explain that to patients. And to put it in perspective, we have not seen any suicides since the drug has been approved. Nevertheless, it is important that we talk to our patients about the risk of suicidal behavior. I think the management of psoriasis or any other disease really depends upon the trust our patients put in us to make them feel that they are part of the human continuum, even though they have psoriasis and that we have tools to help them. And when you earn that trust from a patient, they look to you not just for choices, but they also look to you for guidance. So I say something like this. I know that psoriasis is quite bothersome to you, and you've had many other therapies. I would like to talk to you about a drug called siliq, and I explain what they can expect in terms of efficacy and safety. Then I say, now I have to tell you that there were a few people who were in the trials who had some depression before they enrolled. And during the trial, sadly, four people committed suicide. The investigators didn't find a causal connection to the drug. But as a result of that, I need to go over this form with you, and I show them the form. It's pretty straightforward. And there's a hotline number on this wallet card. I ask them to carry it and call the number and seek immediate attention should they have any thoughts of self harm. While on Salik, I cover all the information that's here and fill it in. Name, address, all of that. We specifically ask if the patient has history of depression or suicide, suicidal thoughts or behavior. And I say, this is all about you having more information, helping you get the medicine you need, increasing your safety during treatment. And then we sign the form and send it in. It can be done electronically, too@salerems.com. I will say that when Siliq first came out, I was skeptical. I was a big biologic writer, and I thought I would never, ever write that drug because of this issue. And I believe that may still be a very common misconception among some dermatologists. And my advice is to register@salikrems.com and give Siliq a try for your appropriate patients. My first patients were those who didn't get better on all of the best stuff we had at the time. And all I will say is, it's worth it. Your patients are worth it. And now, before we close, I want to be sure you get a chance to hear some additional information about the SILIq REMS program and important safety information for SiLIq. The Siliq REMS program physicians must register for the SiLiq REMS program@salehrems.com. Discontinuation or transfer of care must be reported to the Siliq REMS program. This video is not intended to replace all of the REMS requirements. Complete details about the SILIQ rems are available@salikrems.com. Indication Siliq injection is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Important safety information warning suicidal ideation and behavior suicidal ideation and behavior, including completed suicides, have occurred in patients treated with Siliq. Prior to prescribing SiLIq, weigh the potential risks and benefits in patients with a history of depression and or suicidal ideation or behavior. Patients with new or worsening suicidal ideation and behavior should be referred to a mental health professional as appropriate. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation or behavior. New onset or worsening depression, anxiety, or other mood changes. See warnings and precautions in the full prescribing information. Because of the observed suicidal behavior in subjects treated with SilIq, SiLIQ is available only through a restricted program under a risk evaluation and mitigation strategy rems, called the Siliq REMS program. See warnings and precautions in the full prescribing information. Crohn's disease Siliq is contraindicated in patients with Crohn's disease. In clinical trials, which excluded Crohn's patients, one SiliQ patient was withdrawn after developing Crohn's disease. Discontinue Soleik if a patient develops Crohn's disease. Siliq risk evaluation and mitigation strategy REMS program SilIQ is available only through a restricted program called the SiLIQ rems because of observed suicidal ideation and behavior in patients treated with Siliq. Before prescribing SiLIQ, prescribers must be certified with the program. Have each patient sign a patient prescriber agreement form and provide the patient a wallet card describing symptoms requiring immediate medical evaluation. Pharmacies must be certified and only dispense to patients authorized to receive SILIQ. More information is available@saliquerems.com or by calling the SILIQ REMS program call center at 855-511-6135 infections SiLIQ may increase the risk of infections. Serious infections and fungal infections were observed at a higher rate in patients treated with SiLIQ than placebotreated patients in clinical trials including one case of cryptococcal meningitis that led to discontinuation of therapy. Consider risks and benefits prior to prescribing SILIQ in patients with a chronic infection or history of recurrent infection. Instruct patients to seek treatment if signs or symptoms of a chronic or acute infection occur. Risk for latent tuberculosis TB reactivation evaluate patients for TB prior to initiating treatment with SiLIQ and do not treat patients with active TB. Initiate treatment for latent TB prior to starting SilIQ and consider anti TB therapy prior to initiation in patients with history of latent TB. If adequate treatment cannot be confirmed, monitor closely for symptoms of active TB during and after treatment immunizations avoid use of live vaccines in patients treated with Siliq. Adverse reactions the most commonly reported adverse reactions in clinical trials were arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions, influenza, neutropenia, and tinia infections. To report suspected adverse reactions, contact Bauch Health at 1803 214576 or the FDA at 1800 FDA 1088 or visit FDA slash Medwatch. Please see full prescribing information, including boxed warning about suicidal ideation and behavior@siliq.com. Premiumpeed.com.

Join Scott Drew, MD, as he shares his approach to discussing the REMS program with his patients. Dr Drew details how he offers guidance to his patients undergoing treatment for moderate-to-severe-plaque psoriasis, the importance of discussing the patient’s mental health history, and how he explains and contextualizes important information for patients participating in the REMS program.

Join the leading experts as they go in-depth on some of the most important topics in dermatology. Hear invaluable insights on mechanism of disease, treatment options, and more for some of the most challenging dermatologic conditions.

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Discourses in Dermatology

Chronic Spontaneous Urticaria: Mechanism of Disease 

Chronic spontaneous urticaria (CSU) is a skin condition marked by the presence of red, swollen, itchy patches on the skin known as hives or wheals, which typically last less than 24 hours, and recur frequently, for a period exceeding 6 weeks.This video provides a comprehensive look at the underlying mechanisms driving CSU, highlighting the pivotal role of mast cell and basophil degranulation and the central role of the high-affinity immunoglobulin (Ig) E&nbsp;receptor I (FcεRI) pathway and IgE and IgG antibodies in the autoimmune response.Viewers will gain a deeper understanding of both type I autoimmunity and type 2b autoimmunity in CSU and the critical role of Bruton’s tyrosine kinase (BTK), a key mediator in the FcεRI signaling cascade that regulates mast cell degranulation and histamine release. Through this detailed exploration, viewers will learn about BTK's significance in CSU pathogenesis and its potential as a therapeutic target.

Exploration in Chronic Spontaneous Urticaria

<div class="raw-html-embed"><a href="https://d18uhdhjoz8by6.cloudfront.net/DEI_Chart_V4_2655dc7c92.pdf" target="_blank"><button class="h-10 flex items-center justify-center gap-2 cursor-pointer h-[60px] outline-none rounded py-5 px-4 font-semibold bg-blue-250 hover:bg-blue-200 text-white flex mx-auto w-[50%]">Download resource</button></a></div>&nbsp;Chronic spontaneous urticaria (CSU) is defined by the spontaneous appearance of hives, swelling, or both, for greater than 6 weeks, due to unknown causes. In this informative video, learn about diagnosing CSU and the importance of an accurate and thorough symptom assessment, the clinical features of CSU and how wheals and angioedema may present in patients with CSU, and the factors that drive delays in diagnosing CSU.Gain insights into the patient journey, exploring the range of emotions patients experience and the quality of life impact on those with refractory CSU that cannot be controlled with standard therapies. Get a comprehensive overview of the pathogenesis and pathophysiology of CSU, exploring the role of dermal mast cells, basophils, and Bruton’s tyrosine kinase. Finally, learn about the updates and revisions to the international guidelines for diagnosis and management of CSU, including an explanation of stepwise treatment guidelines that endorse an “assess, act, and adjust” paradigm.

Psoriasis mechanism of disease: Insights on treatment options

In this installment of Discourses in Dermatology, Dr Jason Hawkes, a medical dermatologist in the greater Sacramento area, sits down with Dr George Han, associate professor and director of clinical trials in the department of Dermatology at the Donald and Barbara Zucker School of Medicine at Hofstra Northwell, to discuss insights on treatment options for psoriasis.Biologics vs historic systemic immunosuppressantsDr Hawkes begins the discussion by asking Dr Han to highlight the primary role of biologics and their advantages compared to systemic immunosuppressants that have been used historically.Dr Han remarks that our understanding of the immunology of psoriasis has grown significantly over time, and in some cases after medications have been developed. It was initially believed that IL-12 was more important than IL-23 in psoriasis while it was later demonstrated that the inverse is true, with some animal studies showing IL-12 inhibition may actually negatively impact psoriasis treatment.He continues to comment on the ability of biologics to specifically target individual cytokines and antibodies very precisely in the body compared with the ability of small molecules, which target a few amino acid sequence differences among different receptors and cannot be as selective. Patients are often uncomfortable with biologics, wondering why they must inject themselves when they can take a pill that would be much less invasive. He explains that with small molecules, sacrifices must be made because more of the immune system is being blocked; there are more risks to inhibiting a large amount of things as opposed to specifically blocking a cytokine that’s involved in the pathogenesis of psoriasis with a targeted medication.Dr Han links this idea to TNF alpha inhibitors, which have been in use for almost 20 years. TNF alpha is a cytokine involved in a broad array of immune-mediated diseases; as a result, some of these medications have many indications as they’re ubiquitous across a large number of disease states. However, they block more of the immune system, thus leading to more contraindications. He compares this with the newer classes of biologics now available for psoriasis, which target cytokines like IL-23 and IL-17 that are specific to psoriasis.&nbsp;He goes on to explain how he counsels patients who are fearful about negative effects of biologics. He advises them that there are individuals who are born genetically without IL-17 who lead normal lives and may simply be more prone to minor fungal infections, which he finds helps his patients contextualize the effects of taking a biologic.Key points<ul><li>Biologics can target individual cytokines and antibodies precisely in the body</li><li>Small molecules cannot be as selective, thus leading to increased risk as a result of hampered immune systems</li><li>Contextualizing the effects of taking a biologic may help patients who are concerned about taking these medications</li></ul>Addressing safety concerns around biologicsDr Hawkes responds to Dr Han’s commentary by reiterating that historical agents used in psoriasis were broad-acting immunosuppressants that worked because they hampered most of the immune system. While they are effective in controlling psoriasis, they come at the cost of collateral damage to the patient.He believes this has created a paradox when it comes to payers that push strongly to use these broad-acting medications. This tendency communicates indirectly to patients and providers that the newer targeted agents may not be as safe as the older oral medications, and he sees hesitancy to use the newer agents because they’re not traditional but rather are unique molecules created in a lab. He asks Dr Han how he addresses this attitude when it comes to the safety of biologics.Dr Han confirms that there is a lot of apprehension surrounding biologics, which he posits may come from poorly designed or older studies. However, most of these medications, while newer, now have 3- to 5-year data available. They’re also evolutions of older medicines, which means they’re often more narrowly focused. He adds that IL-12 and IL-23 inhibition emerged in 2009, so there is actually a long track record of targeting these mechanisms.He recounts recently seeing a patient on etanercept and methotrexate prescribed by their rheumatologist and notes that rheumatologists are often very comfortable with methotrexate. However, he explains that the risk of liver damage and liver fibrosis from methotrexate is different for patients with rheumatoid arthritis than it is for patients with psoriasis. He recounts a study that demonstrated the highest risk was seen in patients with psoriasis, followed by those with psoriatic arthritis, and lastly, those with rheumatoid arthritis.He feels this demonstrates the importance of communicating with patients that we don’t need to rely on these medications when we have better, more targeted tools available. However, he acknowledges that when it comes to medical economics, there are often different pressures at play.Key points<ul><li>A push from payers to prescribe broad-acting medications may lead to hesitancy in using newer biologic agents</li><li>Most biologics now have 3- to 5-year safety data available&nbsp;</li><li>Biologics are evolutions of older medicines, which means they’re often more narrowly focused</li><li>Proper counseling of patients is important when it comes to explaining the benefits of biologics</li></ul>Weighing the benefits of targeted therapiesDr Hawkes continues the conversation by asking Dr Han if there are clinical scenarios in which these narrowly targeted medications may be problematic when compared to using medications with a broader impact and what may drive him to select a broader-acting biologic over a highly selective one.Dr Han highlights the sequential development from TNF alpha to IL-17 A and IL-23 inhibitors, noting the increasing effectiveness observed on the skin. Despite achieving high levels of clearance, he emphasizes that no medication is 100% effective all the time, leaving room for improvement in efficacy.The conversation then shifts to the importance of treating patients to target, aiming for maximum clearance with biologics. Dr Han acknowledges the need for enhancement in efficacy and considers the trade-offs in targeting specific conditions. For instance, IL-23 inhibitors may be effective for psoriasis but might not be the optimal choice for psoriatic arthritis, which is better addressed by TNF alpha and IL-17 inhibitors according to guidelines.He then delves into the challenges in rheumatology, particularly in assessing joint conditions. Unlike the straightforward evaluation of skin psoriasis with PASI scores, assessing the joints is more complex, and the differentiation between medications becomes more challenging.&nbsp;He recalls case reports when ustekinumab came out that showed patients exhibiting unmasking of psoriatic arthritis. He posits what was likely happening was that patients on TNF alpha inhibitors were getting good control of their psoriatic arthritis, but not their skin. When they switched medications, their skin may have improved, but at the cost of pulling efficacy from the joint. He remarks that a clinical scenario like that may drive towards one treatment versus another.Dr Han goes on to discuss the IL-17 family and considerations about different isoforms, emphasizing the significance of a holistic approach now that we can differentiate and target different aspects of IL-17. He concludes by expressing interest in how these developments will impact clinical practice.To close the discussion, Dr Hawkes reflects on the implications of a skin bias that emerges as a result of skin being accessible. He acknowledges the challenge of making assumptions and extrapolations about joint health based solely on skin findings. He comments that that the immune environment in joints might differ, requiring a broader suppression of the immune system for patients with psoriatic arthritis.He concludes by remarking on the need to learn more about the nuances of psoriatic disease and assess selective therapies to balance the benefits and disadvantages of being too broad or too narrow in treatment approaches.Key points<ul><li>Some clinical scenarios may benefit from the use of a broader-acting biologic over a highly selective one</li><li>Patients with psoriatic arthritis may require a more nuanced approach to treatment selection</li></ul>

Psoriasis mechanism of disease: Pathogenesis

In this installment of Discourses in Dermatology, Dr Andrew Blauvelt, a dermatologist from Portland, Oregon and investigator at Oregon Medical Research Center, sits down with Dr Jason Hawkes, a medical dermatologist from Sacramento, California, to discuss the pathogenesis of psoriasis. Over the course of their conversation, they provide an overview of the immunology of psoriasis, explore the relationship between IL-23 and IL-17, highlight the isoforms that dermatologists need to know, and examine the role of TNF in the pathogenesis of psoriasis.<h5>Overview of the immunology of psoriasis</h5>Dr Hawkes begins with a high-level overview and considers the primary signal that drives the clinical features of psoriasis dermatologists see in the clinic. He notes that IL-17, both IL-17A and IL-17F, is the cytokine that drives the hyperproliferative effects in psoriasis, with IL-23 helping sustain those T cells and making high levels of IL-17. He comments that this serves as the predominant role of what drives psoriasis.Another aspect he considers is the skin once it’s been activated. Once it’s in the hyperproliferative state, it begins making its own signals like IL-17C, IL-19, and CCL20, which go back to the immune system to reactivate dendritic cells and T-cells. This is a feed-forward cycle that begins with the IL-23 and IL-17 axis activating the skin cells and signals coming back that activate the dendritic cells and T cells further, creating a chronic cycle of disease. This serves as the framework by which we can then examine the nuances of psoriasis.<h5>Key points:</h5><ul><li>IL-17 (both A and F) is the cytokine that drives the hyperproliferative effects in psoriasis</li><li>IL-23 helps to sustain T-cells and make high levels of IL-17</li><li>The IL-23 and IL-17 axis activates skin cells with signals coming back that activate dendritic cells and T cells, which creates a feed-forward cycle that promotes a chronic cycle of disease&nbsp;</li></ul><h5>The relationship between IL-23 and IL-17</h5>Dr Hawkes remarks that he views IL-23 as the regulatory signal that helps T cells differentiate into IL-17-producing T cells. Th17 is commonly discussed, but T-17 must also be mentioned since it includes both the CD4+ and CV8+ T cells.&nbsp; He summarizes the relationship between IL-23 and IL-17 by explaining that IL-23 is upstream of IL-17 and helps T cells differentiate into IL-17 high-producing cells. From IL-17-producing T cells, we see both IL-17A and IL-17F. Dr Hawkes also mentions IL-17C, which is produced by keratinocytes as opposed to IL-17A and F which come from T cells.<h5>Key points</h5><ul><li>IL-23 is the regulatory signal that helps T cells differentiate into IL-17-producing cells</li><li>IL-17A and IL-17F come from IL-17-producing T cells</li><li>IL-17C is produced by keratinocytes&nbsp;</li></ul><h5>Isoforms that dermatologists need to know</h5>Dr Blauvelt comments on the number of different isoforms included in A though F and asks Dr Hawkes which key IL-17 cytokines are important for dermatologists to know about when it comes to the pathogenesis of psoriasis.Dr Hawkes explains that there are 6 dimeric cytokines in the IL-17 family, IL-17 A through IL-17 F. These cytokines can pair, so there may be an IL-17 AA homodimer or an AF for example, which is relevant in driving psoriasis. &nbsp;He notes that not much is known about IL-17 B, D, E.He identifies 3 cytokines that are important for dermatologists to pay attention to. IL-17A and IL-17 F are primarily produced by the T cells. The AA homodimer, the AF heterodimer, and the FF homodimer are the key signals from the T cell compartment.From the keratinocytes, we see IL-17 C.He remarks that we don’t yet know the role of the other IL-17 cytokines play in psoriasis, but IL-17 A, F, and C drive the predominant features we see in the immune compartment and in the keratinocyte or epidermal compartment.<h5>Key points</h5><ul><li>There are 6 dimeric cytokines in the IL-17 family (A-F)</li><li>These cytokines can pair, which is relevant in driving psoriasis</li><li>IL-17A, F, and C drive the predominant features of psoriasis&nbsp;</li></ul><h5>The role of TNF in psoriasis pathogenesis</h5>Dr Blauvelt continues the conversation by introducing tumor necrosis factor (TNF). He believes TNF is made all over as opposed to specifically upstream, midstream, or downstream and asks Dr Hawkes for his input on where TNF fits into the psoriasis pathogenesis picture.Dr Hawkes agrees and describes TNF as a very potent proinflammatory signal and a cytokine that changes thousands of genes compared to hundreds with IL-17 and IL-23.&nbsp;This creates a big activating system. There are portions of it upstream; plasmacytoid dendritic cells make high levels of interferon and the myeloid or mature dendritic cells make high levels of TNF, but we also see TNF working much further downstream.He references research from Dr James Krueger’s laboratory that has shown IL-17 has its own impact on the skin as does TNF being proinflammatory, but together, that synergy creates a much more powerful impact. We see other cytokines as working with those predominant signals with IL-23 and IL-17, and they’re working to potentiate or amplify the proinflammatory effect.Dr Hawkes notes that many residents have asked how TNF inhibitors work if IL-23 and IL-17 are so central. He replies that the blockade of TNF helps to indirectly reduce levels of IL-17 because it’s an upstream signal like IL-23. By blocking it, it also blocks the potentiating effects and magnifying synergistic effects that IL-17 has on the skin driving hyperproliferation. Because it’s broad acting, it works in different levels.He also comments on the downside of TNF having that broader impact versus more targeted agents. He describes this as immune collateral damage, but it’s also not a very strong potent inhibitor of that central pathway of IL-17 and IL-23. Those targeted agents have a better way of shutting off the driving signal.Dr Blauvelt concludes by describing TNF blockers as anti-inflammatory in general, which is why they work for a variety of inflammatory diseases. and IL-17s and IL23s as much more targeted to psoriatic inflammation, which is why we don’t see a lot of the side effects seen with TNF blockers.<h5>Key points</h5><ul><li>TNF is a potent proinflammatory signal and cytokine that changes thousands of genes, creating a large activation system</li><li>The synergy between IL-17 and TNF creates a powerful impact</li><li>TNF indirectly reduces levels of IL-17, thus blocking magnifying synergistic effects that IL-17 has on driving hyperproliferation</li><li>The broad impact of TNF can be described as immune collateral damage</li><li>IL-17s and IL-23s are much more targeted to psoriatic inflammation versus TNF blockers, which are anti-inflammatory in general</li></ul>

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Under Your Skin

Interview with Benjamin Lockshin, MD

I'm Dr. Nick Brownstone here with Dr. Ben Lakshin, director of clinical trials at US Dermatology Partners. Dr. Locksheen, great to have you here. Want to ask you a few questions about the practice of dermatology. First of all, how do you advertise your practice? Nick, good question. We actually don't do any formal advertising. We reach out to community doctors, make sure that we've developed a relationship with those providers. And I think that taking care of patients effectively and having the patients advertise for us is the most effective way for us to grow as a quality practice. Love that answer. Second thing I want to ask is about practicing dermatology. I love being a dermatologist, but there's many great medical specialties. So Dr. Lakshan, if you couldn't be a dermatologist, what other medical specialty would you practice? That's an easy question. I think my personality and mindset actually work pretty well with urology. I like the humor. I also like the fact that dermatology and urology both share a lot of similarities. You can manage patients with acute problems or you can manage patients over many years. There's a surgical component as well as a medical component with both of these specialties. Definitely. One thing I love about dermatology is being a surgeon and a medical doctor. Dexter's disease doctor, which urology deals with all that. Finally, Dr. Laksheen, how do you avoid burnout, which I know is an important topic for physicians amongst all specialties, dermatology included. So I think adding a little variety in terms of your daily and weekly activities is helpful. So I run our clinical trial center. In addition, I consult and speak with for a number of companies. So that really just allows me to vary up my weekly schedule. Variety is the spice of life. Absolutely. Dr. Lockheed, great to have you here. I really appreciate your answers. Thank you very much.

Interview with Neal Bhatia, MD

My name is Dr. Nick Brownstone, and I'm here with Dr. Neil Batia, board certified dermatologist. Neil, always nice to catch up with you. Pleasure. Whether it's about dermatology or current events, first thing I want to ask is if you can go back in time. What advice would you give yourself as a first year dermatology resident? Yeah, is back in time. Needless to say, that was back in 95, but I'd probably talk about expectations. Think about your first job, may not be your last job. Think about creating a niche for yourself. If you want to get involved with research or in industry or anything else, just create your specialty, stay in your focus, learn a little bit about everything, but try to stay in a niche that you can be proud of and dive deep into. I think the other thing, too, in residency now, the demands are still very high academic, very high achieving. And I would just try to find some balance, but I think if I could go back again and find that balance, I would say, all right, well, just keep your foot on the gas and not so much on the brake. Great advice. I'm a big fan of the back to the future movies. I'm thinking back to the future Ford. Neil Bocce goes back in time and gives himself advice to be the best resident he could be. God. Well, I would start a better diet. I would exercise more and color my hair more often. So we talked about the past. Now thinking in the future, what innovation in dermatology are you most excited about? Yeah, it's been fun. I mean, my career now is mainly in clinical research, and we've been watching just the innovations of the Janus kinase inhibitors, the biologics, all the strategies to manage itch, which we really didn't have options for. I mean, we were all groomed on topical steroids and all the other innovations that were so focused on active ingredients. But now the vehicles of topicals are really exciting. And I think, too, just the approach to thinking about the process of disease, not just the bandage in front of us. I think there's some really good things that are coming in the pipeline that we also just really have to strategize with. I think dermatologists just need to not be afraid of their own shadow. We got to, again, put our patients interest forward because they're going to come somewhere else if we're not so called comfortable or whatever we want to call it. So I think dermatologists just need to get out of our own shadow and start being aggressive again. Let's switch gears here for the last question. This is something that I always have trouble with. How do you communicate a serious disease, serious diagnosis to your patients? Can you give me some tips? Sure. Actually just happened a couple of weeks ago. First of all, you have to really do these things in person. I mean, you have to put your hands on people. You have to look them in the eye, talk to them, them about the severity of what's happening, whether it be melanoma, whether it be other kind of cancer, whether it be something bolus or inflammatory that they may not understand. Because the problem is if you do it over the phone, they may not hear anything past the bad news, even more so they'll start doing research on their own. And you want to be prepared on how you're going to talk to them about what's in front of them, what the management plan is. But part of medicine is, again, putting your hands on people. Dermatology is got to be with people. And when I was teaching, I used to tell the residents, you cannot leave the room without putting your hands on them, whether you shake their hands or anything else. And delivering bad news is part of that. You have to be able to feel the compassion and know that you're with them and not just giving the bad news. You're part of the bad news and part of the solution. Also, always great catching up with you. Appreciate your answer. Oh, thank you. Thanks for having me. Bye.