This transcript was automatically generated from the video recording and may contain inaccuracies, including errors or typographical mistakes.

Spotting HS: Pathogenesis, Clinical Presentation, and Diagnosis

Dr. Venessa Peña-Robichaux (The University of Texas at Austin Dell Medical School): This is the first section of this HS masterclass. During this first section, what we are going to do is we are going to talk about the pathophysiology of HS to help you better understand how this relates to disease progression and also how it relates to our new emerging targeted therapies.

We are also going to talk about consensus-driven diagnostic strategies so that we can improve our accuracy and diagnosis in order to start treatment sooner for our patients, because what do we want to do? We want to help improve patient outcomes.

Pathophysiology of HS

Starting out with the pathophysiology of HS. Pathophysiology is actually very complicated and we do not quite understand everything in detail. At a very basic level, what you should understand that this is a genetic autoinflammatory follicular disorder. There is follicular dysfunction that basically leads to a susceptibility to follicular occlusion and rupture. Then that leads to a secondary very robust abnormal inflammatory response.

This response can be exacerbated and triggered by other exogenous factors such as:

• Genetic predispositions;
• Hormones;
• Obesity;
• Smoking;
• Mechanical stress and friction; and
• Microorganisms.

Immune Activation in HS

If we are zooming in a little bit more, it is important to know that the inflammatory response involves immunologic mechanisms that lead to broad activation of both innate and adaptive immune cells. With regard to the innate immune cells, there are various cells involved in this inflammatory response, and you can see them listed on the slide there.

The adaptive immune response primarily involves these subset of T helper cells which are listed here, Th17, Th1 and T regulatory cells. It also involves B cells and plasma cells.

This inflammatory response is sent with all of these immune cells leads to an abundance of these pro-inflammatory cytokines which include things like IL-1-beta, IL-12 and 23, TNF-alpha, and IL-17.

TNF-⍺ and IL-17 in HS Pathophysiology

Although, there are a lot of cytokines involved in this pathway, the two key cytokines we are going to discuss today, which are central to this inflammatory response is TNF-alpha and IL-17. Although these both have very distinct immune cell groups that activate them by different pathways, they do act synergistically.

TNF-alpha primarily is secreted by innate immune cells. You see it earlier on in HS lesion development. TNF-alpha also triggers chemokine secretion including from keratinocytes, fibroblasts and endothelial cells. This promotes IL-23, which then leads to further Th17 differentiation, which then produces more TNF-alpha, which amplifies the inflammation further.

When it comes to IL-17, these are primarily secreted by Th17 cells, which are again activated by immune cells. This leads to again production of more cytokines, which then lead to more Th17 differentiation and again creates this inflammatory response.

JAK/STAT Pathway in HS Pathophysiology

With regard to the JAK/STAT pathway, it involves both innate and adaptive immunity, and it is activated by multiple cytokines. When the JAK/STAT pathway is activated, it induces transcription of genes that promote cell proliferation, differentiation, survival and inflammation.

One of the key findings as it relates to HS is that there is a strong induction of STAT1 activation in lesional HS skin. In addition, multiple cytokines are involved in HS inflammation signal through this pathway.

Diagnosing HS

Now that we understand a little bit more about the pathophysiology of HS, let us discuss how we make a diagnosis. Generally, a diagnosis is made clinically. We do a physical exam and take a history. It is important to know that there is consensus-driven diagnostic criteria for HS. This comes from multiple international expert groups and clinical guidelines.

Generally, there is three criteria. Patients must have characteristic lesions in intertriginous areas typically that recur and are chronic.

Nodules and Abscesses in HS

These are examples of some characteristic lesions that we see. You can see some typical nodules in the axillae here, some abscess formation, which typically means there is a fluid collection that often causes drainage.

Comedones and Double-Ended Pseudocomedones in HS

Another finding you can see in these patients is they are susceptible to forming comedones. Specifically, you can see what are called these double-ended pseudocomedones, which are almost like these tiny little tunnels that we see. This is important to recognize because you can see patients with earlier disease start to form these, especially in our pediatric population.

Tunnels in HS

Then, of course, the classic tunnels that we see, which can be inflamed and then can also lead to significant scarring, including the specific scarring we see, which is called bridging fibrosis.

Hurley Clinical Staging System

Hurley staging is often used to describe the type and extensivity of the lesions of HS. It is important to keep in mind, though, that Hurley stage is not necessarily correlated with severity. Just to remind you:

• Hurley stage I is typically described as patients who have nodules with very minimal scarring;
• Hurley stage II is when you have tunnelling with some limited scarring; and
• Stage III is when you have extensive tunnelling and extensive scarring.

As I discussed earlier, it is important to remember that Hurley stage does not equate to severity. For example, you can have patients with Hurley stage I who have an exuberant amount of nodules and abscesses without any tunnels.

Clinical Phenotypes of HS

HS can present with heterogeneous phenotypes. We all know we have seen these patients before. They can look very different. There are many groups that have tried to break these clinical phenotypes down. Personally, I find the phenotypes from the group from Martorell to be most helpful. They have simplified this phenotype.

Clinical Phenotypes of HS

I have some pictures here of what they describe. The Martorell group describes two phenotypes:

• Inflammatory subtype; and
• Follicular subtype.

The inflammatory subtype typically is described as what we think of as your typical HS. Those inflamed nodules and tunnels that tend to drain. Then the follicular subtype are patients that you see more of an acneiform type of presentation, you see more comedones and more of these nodules that you see. Some studies also indicate that when patients present with this inflammatory phenotype, they are more likely to have severe disease and more likely to progress.

Risk Factors for HS

It is also important to recognize the risk factors associated with HS. These include things like sex and race. We do know, for example, that Black women are more likely to have HS. There is also genetic predisposition for patients. About 30% of patients have a familial variant of HS, which is associated with a monogenic mutation.

Smoking is something also related that we see as a risk factor to HS. It is important to understand that although smoking is not a cause, it can be a trigger. Studies have shown that patients who smoke are actually two times less likely to respond to treatment.

Obesity is a risk factor that is discussed a lot. Again, all those studies have shown that patients who are obese tend to have more severe disease. Patients with normal BMIs can have severe disease as well. Again, very important to tell our patients this is not a causal relationship.

Finally, we do know that lower socioeconomic status is associated with HS as well, but this can be a bidirectional relationship.

Early HS Diagnosis Is Critical

Putting this all together, understanding the risk factors of developing HS and how to clinically recognize this condition is key to starting timely treatment. This is important because delays in diagnosis can lead to things like progression of disease, more severe scarring, worsening comorbidities, more surgical interventions that may not be needed, more of a psychological burden. Patients often that are misdiagnosed will get treatments that they do not need. This again, will cause healthcare costs to skyrocket.

Patient Perspective: My Journey to HS Diagnosis

Keeping this in mind, let us now listen to this patient discuss his HS journey. Unfortunately, stories like this are not uncommon, but hopefully we can change that.

Mark Dixon (Patient): Hello. My name is Mark. I am 39 years old. I live in California, and I am here to tell my HS journey. I have had HS since I was around 12 or 13 years old. It definitely started around the onset of puberty, and I just treated it and thought it was acne. As I continued to get older, the condition and the severity of it continued to increase and the symptoms were quite noticeable and painful.

During my teenage years, I would see my doctor and started with the primary care and really was just trying to understand maybe what was going on. The doctor understandably would look at it and look at me and treat it as though it was teenage acne. For many years, that is what I thought. I would go to the office and see the doctor, and he would prescribe antibiotics and topical washes and lotions and creams and all sorts of things. They never, really ever seemed to work.

I would go back, a different one would be prescribed and it was just an endless cycle of antibiotics, washes, creams, rinse and repeat. I was always told I would grow out of it, it was just normal teenage acne. That is how I really lived my life all through my teenage years.

Into my 20s, I started realizing the acne that I had had that was on my face and really more traditional places had really cleared up and I was not dealing with the issues, but the flare ups and the things I was having on my body never really went away. If anything, they were getting worse.

Into my 20s, many of the areas had become quite severe and persistent. I had to really pursue a more extreme level of care. I started seeing dermatologists, I started seeing specialists in everything from allergy to infectious disease to immunology, and anything I could try that was a new avenue to try and figure out why I was getting these incredibly painful long lasting deep flare-up type infections. They were constant.

I would get new ones almost every single day it seemed like. There was just not a day where I did not have a new area that was flaring up. As I continued to try and find treatments, I had to start having surgeries and procedures to remove really constantly infected areas. One area in particular was on my buttock. After a number of procedures, the wound was quite severe and required packing and wound care. It was something that I could not manage because of just where it was located.

A friend of our families who was a nurse was helping me on her side time to treat and care for me. As she saw what I was going through and she saw what the condition was, she started asking around in her circle of friends and medical network that she knew. One day she came back and asked if I had ever heard of HS? Through all my appointments, through all the doctor visits, that condition had never been brought up.

She had printed out something from online. It was a description of what the condition was. As I read through it, it sounded exactly like what I was experiencing, flare ups on the trunk of my body, under my arms, all consistent, sinus tracking, the whole all the hallmark traits of HS were finally described in one place in a diagnosis.

At that point, I was convinced I knew I had it. As I took that information and started doing my own research, I found a doctor who had an HS clinic. When I saw the doctor, he confirmed almost immediately that it was HS. That was really where the journey to treatment started with effective treatments.

Over the last 10 years, I have been on three different biologics. Still have the condition, I still get flare ups. I still have to go in and get the steroid injections or sometimes have a drainage. For the most part, my quality of life and the severity of the condition has improved dramatically.

Patient Case 1: 50-Yr-Old Female

Dr. Peña-Robichaux: Okay. We are going to move on to the interactive part of the session now. What we are going to do is I am going to present a patient case and then present you with some questions for discussion. Then we are going to break out into some small groups and have discussion around the table.

This case is actually a personal patient of mine. I saw them a year or two outside of residency. She was a 50-year-old female, Hispanic woman. She had over 20 years of history of very severe symptoms. She had these chronic and recurrent flares primarily on her pannus mons pubis, labial area. She had been to the ED multiple times and had tried multiple topical medications, multiple antibiotics.

When I met her and we started discussing treatment with biologics, she was very hesitant because she was worried because she has been told this whole time she had cellulitis, which is an infection. How possibly could she start a biologic?

Small Group Discussion on Patient Case 1

For this case, what we would like to discuss are these questions:

• What features of the history support the diagnosis of HS specifically to this case;
• In what ways do you think this patient has been impacted by her untreated HS;
• How does timely diagnosis play a role in the clinical course for patients like this; and
• Based on your understanding of HS pathophysiology, how would you approach clinical management?

We are going to take about five minutes to have discussion.

Dr. Mikael Horissian (Geisinger Medical Center): I do see one question that has been asked by you all that I can explain as we are going. The question was, can you explain Hurley stage IB/C, and if this is helpful clinically for insurance approvals of systemic for choice of antibiotics and treatment or choice of treatment in general?

I personally do not use the modified Hurley scoring system. It is just a little bit more cumbersome, although I do think it is better than the one, two, three. As far as insurance goes, I find that they are looking for the word moderate or severe. I will usually add that to my note and the descriptions of what they are going through and how it impacts their life. I have not had an issue with approval in that regard.

Does anybody want to message in any of the answers to the questions here about how timely diagnosis plays a role in the clinical course or how you would approach clinical management of this patient?

The recurring nature, the location of the spot, all support the diagnosis. The impact of untreated disease can be multifocal one. It can be not understanding your disease, not understanding what causes it, having the misdiagnosis of recurrent infections. That leads to inappropriate treatment or not seeking the right person for treatment like dermatologist or NHS specialist.

Timely diagnosis plays a huge role in the management of HS, because once it gets to a point where there is a lot of scarring and tunnelling, it is really hard to reverse. It is impossible to reverse that, in my opinion. The earlier we can start people on appropriate treatments, the earlier we can stop that cataclysmic cascade of inflammation and scarring and prevent the disease from worsening, really disease modifying in a sense.

That is how I think the earlier the better. That is multifocal because the primary care physicians and the OB/GYNs and the surgeons need to be able to identify what it is and send it to the right people. Otherwise, there is the delaying care of eight to 10 years that we have talked about in prior studies.

Then based on pathophysiology, how would I approach the clinical management of this patient? Based on that photograph on the last slide, has pretty significant inflammatory disease. We need to treat that with something that is anti-inflammatory. To the patient's question of if I have had recurrent cellulitis, would not this make me worse? That is a valid question, a valid point. Because HS is an inflammatory disorder, we use the anti-inflammatory agents, biologic agents, those kind of things to quell the overactive immune system at the level of the hair follicle, and prevent the disease from having as frequent flare ups or having as much inflammation there, as much drainage or having spots happen as often.

Does anybody else have any questions on diagnosis?

I have got a question for the virtual group, and you can pose your answers back as a question to me. How do you diagnose HS? What is your criteria? Do you find that it is usually diagnosed by the time it comes to your door or you are the first one making that diagnosis?

I know in my experience, I have a lot of patients who are actually diagnosing themselves because their primary care doctors told them it was just an infection, but then they go on TikTok and find that out. That is one thing that social media has been positive for, for my patients.

A couple of comments here. I see the psychological impact of recurring episodes is huge. Yes, I absolutely agree with that.

Okay. This is a good one. In clinical practice, what is the average time to diagnosis for HS patients? What would be the comorbidities that matter the most when planning treatment?

Great question. It really depends on when you catch the patient. If you look at an average pool of all patients, the delay is still pretty similar of eight years. I find a lot of my own patients are getting diagnosed earlier, whether that is because we have done a lot of work teaching the primary care doctors in the office and the pediatricians or, like I mentioned, social media.

I feel like that is going down. If you look nationwide, it is not necessarily going down for people. Comorbidities, obesity, smoking, PCOS, the metabolic syndrome things. Those are things we should be aware of because some of our therapies can help more than one thing. I find a lot of these patients are not necessarily seeing their primary care doctors. So I function as one. But plugging them back in with primary care can be helpful to address those things.

What is the impact of inflammation on other body systems?

Another great question. Similar to psoriasis, we usually think things are skin deep until we find out there is more to it. Similar to how psoriasis we found out was a systemic inflammatory disease, the same thing is true with HS. People can have other inflammatory conditions like inflammatory bowel disease, ankylosing spondylitis, or even just inflammatory joint disease.

A lot of these patients, particularly those with severe disease, have leukocytosis and anemia of chronic disease. So the impact is definitely there on other systems.

Another good question. Other than Hurley, what else have you used for diagnosing/determining severity?

I actually based the severity not off my own impression of the patient but off of how they describe their disease. I try to ask questions like, is this keeping you from going to work? How many days did you have to call off work in the last three months? Is this keeping you from going and doing what you want, like going to the restaurant and the gym or having sexual intercourse? If there are things that it is changing their life in a negative way. That is at least moderate severity, if not more.

If they have one flare-up a year, does not bother them at all and it comes and goes and they are not bothered by it. They would be okay taking antibiotics for a couple of weeks when that happens. That is mild disease. But a lot of people fall into the moderate to severe category.

If we base it solely off of what we are seeing, sometimes we can misjudge patients, and that is for multiple reasons. We have our own biases. I also think that HS is a disease that changes day by day. We do not always see them in their worst moment. They may have flared up a week ago and not the week that we have it. I use a lot of patient-reported outcomes to determine how much this is affecting them and in turn putting their severity in my notes.

Thanks, everyone.

Small Group Discussion on Patient Case 1

Dr. Peña-Robichaux: Let us just recap what different discussion points we were talking about. I know some of the tables I was discussing, we were talking about how it can be difficult to have that discussion with patients about what they have been told in the past versus what we are telling them at the visit.

For patients who have been told they have had an infection, they have cellulitis, that is always a difficult conversation. To get them to understand that actually, no, this is something different and that can be challenging. What some people were saying is just building a relationship with a patient to gain their trust and also interacting with other providers, primary care so that everyone is on the same page with the diagnosis.

Did you guys have any good discussions?

Dr. Leandra Barnes (Stanford University School of Medicine): Yes, at one of our tables, we were talking about that buy-in, that shared decision-making with such severe disease and with her maybe being more concerned about it being an infection and being more open to antibiotics, even considering like an IV ertapenem bridge to surgery or bridge to another biologic medication.

Dr. Katrina Lee (Keck School of Medicine of USC): Yes. Then there were some diagnostic challenges that were discussed. What came up is how do we differentiate acne versus HS? In all honesty, some patients have both, right? We know acne and HS are comorbid conditions. With HS, a lot of it is listening to that history of the chronicity.

For all of my patients with severe acne, I usually will get them into a gown and check them head to toe because you might find HS. Looking behind the ears in those intertriginous areas and looking for subtle clues, because we know that HS waxes and wanes. They might be coming to you on a day maybe where their HS is quiet and controlled and looking for subtle clues, is there any atrophic scarring in that intertriginous area? Do we see those double headed comedones and things like that can be very helpful.

Dr. Peña-Robichaux: This patient, I still see her to this day. Just to update you guys, I gained her trust. We got her on adalimumab and she got somewhat better. Then we transitioned her to infliximab and then I got her to surgery. We removed all those areas that you saw in the photograph, and she is completely clear. She continues to be on infliximab to this day. That photograph, I believe was probably from eight or nine years ago.

She did actually lapse in insurance and came off her infliximab for a bit and started having a little bit of recurrence. We went back and did surgery again. Now she is clear. She is doing really great.

Patient-Centered and Long-term Management Strategies in HS

Dr. Lee: Okay. We are going to move on to the next section, and I will get us started here. The next section is patient-centered and long-term management strategies in HS. The goal of this section is to really help provide you with tools to help you formulate comprehensive care plans that take into account patients’ comorbidities and their quality of life.

Addressing Comorbidities in HS Care        

We are going to jump right into comorbidities. We know that HS, as we discussed in the prior section, is a chronic inflammatory condition of the skin. But if we stop there, we are really underestimating its burden. Patients with HS have not only severe tunnelling sometimes, severe inflammation of their skin, lots of drainage and pain, but they also face high levels of systemic inflammation and high comorbidity burden.

It is not uncommon for a patient to have concomitant cardiovascular, endocrine, metabolic, gastrointestinal, MSK, or even psychological comorbidities. I have actually included a QR code here in the upper right corner. This is a nice comprehensive guideline on evidence-based comorbidity screenings that were put together by the US and Canadian HS Foundations.

Screening and recognizing comorbidities remains really central to delivering optimal care.

Cardiovascular and Metabolic Screening

Diving specifically into cardiovascular and metabolic screening. Patients with HS have increased risks of hypertension, dyslipidemia, diabetes, metabolic syndrome, and for female patients, polycystic ovarian syndrome.

As a dermatology provider or dermatologist providers out there, many of us are not necessarily checking a blood pressure or lipid panel and definitely not doing ultrasounds of the ovaries. This is where it can be really helpful to partner with your patient's primary care provider to help screen for comorbidities.

At my institution, what we actually do is we provide the patient with the handout that has a list of all of the comorbidities that I would like their primary care provider to screen them for. So they will take that over to their primary care provider so they can get that comprehensive screening.

Inflammatory Comorbidities in HS

In regards to inflammatory comorbidities, epidemiologic studies suggest two to three times higher risk of inflammatory bowel disease. Many patients may also suffer with joint pains. I do not know if you have asked your patients. Many of them tell you they have joint pains, and a lot of those patients may have pains from an inflammatory arthritis. Some of these patients may come into your clinic already having been diagnosed with IBD or inflammatory arthritis.

If they have not, it is important to screen your patients and ask those questions about abdominal symptoms, GI symptoms and joint pains. What is really helpful is if you have a patient that has a comorbidity like inflammatory bowel disease or inflammatory arthritis, you can then prioritize targeted therapies to target both of those disease states.

For example, if I have a patient that is coming in with a history of Crohn's and HS, I may be trying to reach for that TNF-alpha or even off-label upadacitinib to target both of their comorbidities.

On the flip side, we also want to think about comorbidities in the sense of what prohibits from using or we should caution using certain biologics. For example, if a patient has heart failure, I might try to kind of prioritize IL-17. Or if a patient has a history of lupus, I might try to steer away from the TNF alphas and prioritize an IL-17.

Psychological Comorbidities in HS

Research has shown that people living with HS are at significantly higher rates of depression and anxiety. Actually, the literature suggests that this risk stands true across all severities and stages of HS.

What can be really helpful is screening your patients with a Patient Health Questionnaire two, which is a quick tool. It takes about one minute to complete, and it is scored from zero to six. If your patient has a score of three or higher, you can then either follow-up with a PHQ-9 or refer off to a mental healthcare professional for further workup and treatment, if needed.

A Multidisciplinary Approach Is Essential

This slide is really just here to remind us that optimal outcomes in HS often depend on a multidisciplinary approach. As dermatology providers, we really can make an impact in improving patient's skin and quality of life. When we partner with other specialties, we really can have things optimized to deliver truly comprehensive care.

Lifestyle Modifications in HS

Then just a note on lifestyle modifications, which many of your patients may ask you about. It is helpful to remind them to use gentle and fragrance-free products. Many of them at baseline have very sensitive skin, especially if they are having a lot of drainage or open wounds, loose and breathable clothing like 100% natural fibers such as cotton, bamboo and linen are generally better tolerated. If your patient cannot do rigorous exercise because they are in so much pain and they are having a lot of drainage, you can recommend alternatives like swimming or yoga.

Then I also list healthy weight management and smoking reduction and cessation here, which are definitely important for overall health and may help improve HS symptoms. I put an asterisk because it is important to really wait to discuss those sensitive topics until you have really built that rapport with your patient. A lot of patients have been told that their weights and their smoking is the sole cause of their HS, and we know that just is not the case. So really building that rapport before you dive into some of those more sensitive topics.

I am going to pass the mic on to Dr. Barnes.

Beyond the Skin: Quality of Life and Barriers to Care in HS

Dr. Barnes: Thank you so much, Dr. Lee. Now we are going to transition to quality of life and barriers to care for HS.

I know when a patient walks in the room, we really are just seeing the tip of the iceberg. We may see some painful nodules, abscesses, some scarring and some sinus tracts or tunnels, which is the better term that we use now and drainage and odor. What is really lying beneath and what is really driving a lot of this suffering is the chronic pain, the depression and anxiety, the social isolation. That is also related to stigma and embarrassment that truly impacts all relationships, both work and personal.

Address Barriers in HS to Ensure Access

HS actually has some of the highest scores for burden in quality of life. DLQI, which is a Dermatology Life Quality Index. Some of the scores for HS, as you can see in this image to the left, are so much higher than other conditions that we treat, even urticaria, which we know can be very itchy and keep people up at night and atopic dermatitis and psoriasis.

These all are compounded by the barriers that our patients are experiencing. This is a large part of the research that I do. In a study that I did with one of my mentors, Dr. Haley Naik at UCSF, we identified structural barriers, healthcare provider barriers, and also patient barriers.

As you can imagine, for anyone from an international health system, top one probably does not apply as much to you. Health insurance coverage in the US is really difficult. For a lot of our patients, especially those from lower socioeconomic status, this drives a lot of barriers to even accessing a dermatologist and accessing the FDA-approved medications that we know can really help them.

There are costs, not just the costs for paying for medications, but wound care. The cost of missing work because you live four hours away from an HS specialist or a dermatologist. Just thinking about all the ways that these can be compounded.

What are the healthcare provider barriers? I do a lot of qualitative work as well. Unfortunately, we have heard that some of our colleagues have mentioned to patients or size of disgust when they see their HS or just not even wanting to touch or examine, that really gets internalized and makes people want to avoid health systems altogether. Our attitudes can play a big role in breaking down some of those barriers for our patients.

I know we do not have a ton of time, but it is really important to try to address a lot of these barriers. I previously had a QR code that took you directly to the HS Foundation website, but if you can Google HS Foundation prior authorization templates, they have already done a ton of work to make accessing these medications so much easier for patients. You can use these in terms of prior authorization. Almost attaching a letter of medical necessity to the bottom of your note.

A lot of times what dictates, what gets covered is if the patient actually has moderate or severe disease, and our notes, if they are not detailed enough, describe the areas of involvement, describe the suffering that patients have, missing work, needing to be on disability. Then that is almost a disservice in getting that medication for our patients.

Outside of just what is covered by insurance, there are some other financial assistance programs that a lot of our industry partners have in place. There are patient assistance programs. There are also free drug programs and linking your patients with those or offering to someone in the clinic, like an MA can look things up with them and just see, “Okay, we know your insurance did not cover this, but here is another option to make sure that it is accessible.”

If you do, unfortunately get that denial, please do the peer to peer. There are so many times where it is almost an automatic denial at times, and all you have to do is hop on the phone and advocate and say like, “I am a dermatologist, I take care of patients all the time, and this patient has some of the worst HS I have ever seen in my life.” This will truly improve their life.

Then there is also support navigation just outside of seeing you in clinic, sometimes it is hard to coordinate with primary care and with you and with surgery. If there are models that your health system allows, like if there is social work that can help patients navigate this, that is really helpful.

Then also addressing barriers. Again, there are so many social determinants of health or drivers of health that are before a patient even comes into the visit. Even asking about food, transportation, housing. Some of our patients are trying to decide between buying groceries and buying that medication. If we never ask, then a lot of times they do not volunteer.

Incorporating Quality of Life Into HS Care

To quickly incorporate some of these things that we can help to improve the quality of life, just listening and being empathic as best as we can, especially being gentle with physical exams.

This is just a picture from my clinic in Emeryville in the Bay area. It is really unfortunate if you are draining and you sit down on that really thin paper that is going to stick. So trying to make sure that there is a chux so that patients feel a little bit more comfortable if there is draining that, they are not going to have that uncomfortable movement when they are rotating for you.

A pillow. This is a painful condition. So providing that just allows someone to adjust the weight as they need. Then I also always provide an extra blanket, especially if someone is a little bit on the larger side and the gown is not covering as much. It helps provide some sense of modesty if they are able to use an extra blanket to drape.

Always assess the areas of involvement, count lesions if you can. This is all important for advocating in your documentation. Multidisciplinary care as we have discussed is important. Then support groups. There are so many support groups online for our patients to connect with even outside of the visit. They can be a real source of strength and resources as well.

Pain Affects Quality of Life the Most, so We Must Manage It!

Then last. This is a busy slide that you do not need to digest. Pain. Pain is one of the most impactful symptoms of HS. Please ask about it. Please try to address it. First line would be over-the-counter Tylenol and NSAIDs like ibuprofen and naproxen sodium. There is a ladder that you can go through. Please feel free to use this resource. There is also a wonderful article that summarizes these as well.

Patient Case 2: 35-Yr-Old Woman

With that, I will take it to our case. We have a 35-year-old woman who presents with recurring and tender bumps in the groin inner thighs and axilla, every one to two months for six years. One area is raised and drains from two different openings. She reports that she is missing work due to pain. She lives with her husband and her two children who are young and have a lot of needs, and her uncle has always had boils, a.k.a. there is a family history of HS.

The past medical history. She also has pre-diabetes, PCOS, acne and she notes that her HS is a little bit worse or she has acne flares around her jawline and she also has flares around periods and reports some depression. She is currently on metformin for her pre-diabetes and tretinoin for her acne, and she does not have any known drug allergies.

Small Group Discussion on Patient Case 2

Now we will just like to take a few moments to discuss this case, especially since HS is frequently associated with systemic diseases. What additional comorbidities would you screen for? How might her PCOS and prediabetes play a role? What additional questions would you like to ask her to see how HS is impacting her life? How might you educate and empower her with self-care strategies? What social determinants of health may influence her treatment decisions? What resources and interventions could you help provide to address these barriers?

With that, we will go out into the group and discuss.

Dr. Horissian: Okay. Virtual audience, what do you guys think? We have got a couple questions up here on the screen. What else should we screen for? How might PCOS and prediabetes influence your treatment management?

Personally, it would make me think about if she was not on metformin, potentially starting her on metformin to both help with the prediabetes and the HS. Since she is already on metformin, we could consider going up on that dose for the prediabetes. That is one option.

PCOS would make me think, is she having flare ups with cycles, are the cycles irregular, or might she benefit from spironolactone, which could help with some of the symptoms of PCOS and hirsutism? Depending on the age and other comorbidities or oral contraceptives, a good option for her.

There is a lot of different options based on the comorbidities that we could think about in addition to biologics. What questions would you ask to better understand how it is affecting her life?

Personally, I usually ask them just point blank, how is this affecting your life? Then they sometimes break down in tears and tell me I have not been able to go to work or have not been able to be with my partner or things like that.

There is two good questions here. I am just reading it. Do you find certain drug classes work better for certain morphology types? For example, IL-17 over TNF for draining tunnels.

Potentially yes, I do think so. We need more data on that to really prove it. It is not just anecdotal evidence. I do think that draining tunnels might be more helped by IL-17 inhibition.

The second question is Hurley is a flawed system, especially for assessing response. Do you use a different scale like the HS PGA or IHS4 in clinic?

I know several people do use different systems. I usually do not unless the insurance comes back and tells me I need a specific measure. Those are really helpful measures, particularly in clinical trials. But in a busy derm clinic, counting every single abscess or nodule, not always practical. I generally just base it off of what the patient tells me and clinical photographs. I take clinical photographs at every visit and compare. Again, those are just a snapshot in time.

To your point, you do not go backwards in Hurley staging. So it is not a great system other than giving it a number and getting insurance approval with that. I usually base it off of do I feel like they are having less inflammatory lesions? Are they having less frequent flare ups? How many flare ups do they have a month? Those questions let me know if they are really getting better or not.

Great cases and pearls. Can you talk a little bit about sweating? I often think about Botox in my more mild patients, but maybe I should be thinking in severe patients too.

I agree. There are some studies that show that Botox can help with the sweating, follicular occlusion, the moisture, the rubbing. I definitely think it can play a role in some patients. I do not think it is going to reverse somebody that is stage III. If it really is helping with the disease, it would probably be more helpful earlier on in disease. But could be helpful in later stage if they have excessive sweating.

Then maybe you will get to this, but can you talk about goal dose of metformin for HS?

Yes, we do not have that specifically in the talk, so I am happy to answer that. It depends on tolerability. I have seen people on a pretty high dose of metformin for their diabetes. When I usually do it, I usually do 500 once a day up to twice a day. I find two pills a day, so 1,000 milligrams a day tends to be where most people balance out from a side effect profile standpoint.

When I have gone above that, they have usually gotten sick from it. Even some people, the two pills a day just does not work well, so we do one 500 milligram dose per day.

Great questions. Do you guys have any other questions out there? Okay. I see one here. Talking about a patient that has a history of a recurrent solitary nodule of the groin and buttock, and one scar on the buttocks. You suspect this is HS, which aligns with the possible underlying ovulatory dysfunction that you are evaluating?

Yes, I agree. Usually when you have recurrent lesions in the common hot spots and they keep coming back and draining or even scarring, that is usually HS. I agree with you on that.

Are there any social determinants of health that influence treatment decisions, or any resources or interventions that can help you or your patients?

Small Group Discussion on Patient Case 2

Dr. Barnes: This was pretty fun. Okay. Great. Let us go ahead and do a recap. We heard some really great discussions amongst the tables. People picking up on the fact that she has PCOS. She has acne with perimenstrual flares. Spironolactone would be a great way to address that. Also making sure that we screen for other comorbidities like maybe some arthritis or also IBD would be really important as well.

Dr. Lee: On the point of PCOS, a good alternative or some patients that are on spironolactone and birth control and that came up in discussion. What is important to remember is not all birth controls are helpful for HS and some can actually worsen symptoms. When you look for birth control, we really want to look for one that has that newer generation progesterone. That fourth generation progesterone generally like drospirenone that has anti-androgen properties. If you are looking for birth control that you would try to look for a newer generation progesterone.

GLP-1s came up in the questions. A lot of questions came up on GLP-1s. It is a very hot topic in general, and it has shown some benefit for a few disease states like psoriasis, even HS chronic wounds. Right now we just have very preliminary data. Hopefully, we have more controlled trials, but it can be helpful to leverage in those patients who have comorbid obesity, sleep apnea, diabetes. I find it helpful to work with the patient's primary care provider to access those medications if they are a good candidate.

Dr. Peña-Robichaux: One of the interesting things we were chatting about with one of our groups was when you do have patients with PCOS and are on these hormonal therapies and they decide they want to try to get pregnant, often you get the question, well, what is going to happen when I come off my medication? What is going to happen during the pregnancy?

Just talking about how to counsel about that. I mean, generally pregnancy, I always tell patients is we really do not know. Some patients actually go into remission. Some patients things stay for the course. Some patients might flare, but just letting them know no matter what you are going to support them, their therapies that they can continue if they need to during their pregnancy.

Also just being aware that patients who have HS and who go through pregnancy, we do see higher rates of some complications with these pregnancies, higher rates of gestational diabetes, preeclampsia, need for caesarian section, things like that.

Dr. Horissian: Piggybacking off of your comfort in the exam room technique, the chux and the pillow are really good. One thing my mentor taught me was to do the exam. If you are not going to inject or do a procedure on the patient to step out, let them change in a normal clothes, and then you talk like a normal human instead of a naked patient. That is something I have incorporated too to help it feel a little bit more normal.

The Latest Advances in HS Management

I get to talk about the fun stuff. What are we going to do about all the HS that we have now diagnosed?

[00:58:25]

FDA-Approved Biologic Agents for HS

Okay. This first slide compares our three FDA-approved therapies. We have adalimumab. It is usually dosed Q weekly. It is approved 12 and up. Then the dosing is right there on the slide. You have 160 milligrams on the first day and then 80 milligrams Q15. Then you can do 40 milligrams Q weekly or 80 milligrams every two weeks. I personally do the weekly dosing. It is approved in our pediatric patients and the dosing is on there too.

Secukinumab, a different mechanism. It is an IL-17A inhibitor. It is dosed every four weeks usually, but you can go to every two weeks in patients that need that. Then one new thing this month is that secukinumab was approved for 12 to 17 year olds. We now have two agents approved for our adolescent patient population. I treat a lot of kids, so it is great to have more options.

Then bimekizumab is the newest on the block. It is an IL-17A and F inhibitor. It is dosed every two weeks and then it is every four weeks after the introductory 16-week period.

Patient Candidates for Biologic Therapy

Looking at who is a good candidate for biologics. I really base this off of the questions that we have been getting posed, which is what defines moderate or severe. If somebody is having frequent flare ups, the flare ups are interacting with their life. They are not able to have sexual intercourse, they are not able to live a normal life and go to the gym or go to a restaurant because of fear for leaking or the flare ups every week, and they never have a free period. Those are all reasons to do it.

If somebody has draining tunnels, that is something that is going to need a stronger treatment. The earlier we start these, hopefully the earlier we can prevent the scarring and tunnelling and progression of disease that comes with it.

You have to take into consideration a bunch of things. What is the patient's preference? What is their age? Do they have other comorbidities that might dictate your treatment options? You marry all those together like we would for any of our patients to find out what is the best option for our patients.

PIONEER I/II: Adalimumab for Patients With HS

Delving into the data a little bit more. Adalimumab was the first one to get approved. This is their primary endpoint here. Just to take a pause, the primary endpoint in most of our HS trials is the HiSCR 50. What that means is that there is a reduction in the number of abscesses and nodules by 50%, and no new draining tunnels. It is not a perfect measure, but it is the best we have got.

Here you can see that at week 12, that was their date of primary endpoint. In PIONEER I and PIONEER II, the treatment arm was significant. About 41% to 58% of patients achieved a HiSCR of 50 compared to placebo. Why is there a difference between PIONEER I and PIONEER II?

Well, one potential is PIONEER II actually allowed patients to be continued on oral antibiotics. That might be why PIONEER II is a little bit higher. It is also probably more realistic of what we would do in practice. You are not just going to pull somebody off because you are starting a biologic.

PIONEER I/II: Safety of Adalimumab (Wk 13-36)

This is the safety data from that trial for their phase II part, where they randomized people that were in placebo, back to the treatment arms and placebo and people that were on treatment arms to placebo. There were not any big new safety signals from the original 12 weeks.

SUNRISE and SUNSHINE: Secukinumab for Patients With HS

Moving on to SUNRISE and SUNSHINE, which were the secukinumab trials. This is 52-week data. Their primary endpoint was at 16 weeks. A little bit different than the PIONEER trials. They also required five lesions instead of three. They had two different dosing regimens compared.

You can see that about 60% or so of people on the treatment arms get to that HiSCR 50.

SUNRISE and SUNSHINE: Safety of Secukinumab

Looking at the safety of the drug. Again, no huge safety signals by comparison to placebo. Did have a few more fungal infections, particularly candidal infections, which makes sense with the mechanism of action, IL-17 important for fighting off fungus. Most were treatable. And IBD cases in the SUNRISE trial.

BE HEARD I/II: Bimekizumab in Patients With HS

Then moving on lastly to bimekizumab. Bimekizumab, similar structured trial, in that patients had to have at least five lesions in two different locations. Two different dosing regimens were done. In this first data set that I am showing here, this was where they had a more stringent criteria. Patients could not be given any antibiotics or increased on their antibiotic dose, or else that was considered a treatment failure. You see about 50% of patients or so achieved HiSCR 50.

BE HEARD I/II: Efficacy at 48 Wk

When you look at longer term data and a little bit less stringent, you can see that that number goes to almost 80% for HiSCR 50. One of the coolest things to highlight here is that for the first time, we are talking about HiSCR 75. This reminds me of psoriasis where we used to talk about PASI 75. Now we are talking about PASI 90s and PASI 100.

The bar is getting raised in our clinical trials as to what we want. We do not just want a 50% reduction in abscess and nodules. We are looking at what happens when you have 75% or 90% or 100%. I am really excited for what is to come.

BE HEARD I/II: Safety of Bimekizumab

Looking at safety of bimekizumab, again, very similar safety profile to placebo. We have more candidal infections in this one.

Emerging Therapies for HS

Really exciting to me is what is to come. We have here listed all the later phase medications. You can see that there is a bunch of different mechanisms. We have got JAK inhibitors. We have got an IL-36 inhibitor. We have oral BTK inhibitor. We have another IL-17A and F inhibitor. We have a topical agent. We have oral agents. We have subcutaneous agents. It is an exciting time for HS. There is a lot that is coming out and hopefully a lot more options than we will have other than the three that we currently have.

Beyond FDA-Approved Therapies for HS Management

These are some oldies, newies and goodies. I will try to touch on some of the questions that you all had while I am doing this slide. One oldie but goodie can be infliximab. It is not FDA-approved for HS. The dose that most people find helpful is usually higher than the dose we use in psoriasis, somewhere between 7.5 and 10 milligrams every four to six weeks. That can be really hard to get approved depending on the insurance, but I find infliximab very helpful for those patients that do respond to a TNF, but maybe bigger in size and a more weight-based dosing would be more helpful.

Roflumilast is not universally helpful, but there was a question in the chat about using apremilast. I used to use apremilast until I found out about roflumilast. Roflumilast is generic, so it is available for pennies on the dollar and people can use GoodRx or other things to get it. It does not work for everybody. I do not think it is as heavy hitter as everything we have talked about so far, but it can be a good intermediate or a good add on to therapy.

Then we touched on this with the Q&A session. Spironolactone, metformin, GLP-1 agonists are all helpful. The biggest takeaway with HS is you do not have to use one agent. You can use multiple agents and tack them on and tackle different parts of the HS pathogenesis.

Surgical Management of HS

I would be remiss. I do a lot of surgery. Does anybody do HS surgeries in this room? Okay, a handful of people. Awesome. Hopefully after this talk, you will be doing even more.

Medicine is a really helpful tool and is one of the most important things. But surgery can also be really helpful in something that is in our wheelhouse to do small procedures like deroofings or larger procedures like excisions. I find it best for tunnels that are not responding to biologic therapy or abscesses and nodules that keep recurring despite our best therapies.

My tips, if you are ever going to do an HS procedure, is it is going to take more anesthesia than if you are taking off a mole on somebody, so anesthetize well.

Do not forget about secondary intent. You do not have to close things up. The body is really good, particularly in intertriginous areas at healing. After the surgery, people have limited morbidity because they can move their arms. They are not tacked down with sutures.

Petrolatum is key. The more moist the wound can be, the better it will heal, and the less pain and irritation patients will have. I will rarely jump to surgery first. Most people need a medication first, so that we can quell the disease and then surgically remove what is gone. I also think this helps with surgical outcomes and they have less chance of recurrence and quicker healing.

SHARPS: Adalimumab + Surgery in Moderate to Severe HS

There was a good trial called the SHARPS trial, which is helpful. If you ever send a patient to a surgeon, a lot of times they want to stop the biologic because they are worried about infection risk and those kind of things. You can always show them this study, which showed that the treatment arm that had adalimumab plus surgery compared to placebo plus surgery did better in all regards, both surgically, medically, and there were no increased risks of any infections, complications or bleeding after the surgery. I keep all my patients on their treatments when I do surgeries.

Shared Decision-making in HS Management

Okay. Shared decision-making is important, particularly when we are picking medications. I might think I have a good plan in my head, but if the patient does not want to do injections, we have to tweak my entire plan. It is important to have that shared decision-making, let patients lead it. I usually tell patients they are the captain of the ship and I am their first crewmate. I give them the options and then they tell me which direction we are going.

You have to think about economic needs. You have to learn their goals, their preferences, earn their trust. Do not do the larger surgery you have ever done for the first time. Start small, build their trust and go from there. Then having help with medication access and support can be really helpful.

Patient Case 3: A 17-Yr-Old Girl

That takes us to patient case three. This is a 17-year-old girl diagnosed with HS four years ago. Her symptoms were managed with episodic antibiotics. She has on her buttocks, vulva regions and inguinal areas, a lot of indurated plaques that have pustules on them. She has focal taught nodules, a lot of drainage when you press on it. She is getting ready to start college and she is worried about managing her condition when she is going to be living in a dorm and adjusting to a new academic environment.

She has frequent flares and persistent pain, which have already caused her to miss classes and social activities in high school. She says she is excited about college, but she is scared her HS is going to hold her back. She does not want to miss out on opportunities and feel different from everyone else.

Small Group Discussion on Patient Case 3

For our small group discussion, what management decisions would you encounter with this patient's case? What factors are you considering when you want to select a treatment for this patient?

Dr. Peña-Robichaux: Hello, virtual audience. This is Venessa here. I am looking through your questions. Okay. I have a question here. It is two questions. Do you find certain drug classes work better for certain morphology types? For example, IL-17 greater than TNF for draining tunnels.

Then second question, Hurley is a flawed system especially for assessing response. Do you use a different scale like HS PGA or IHS4 in clinic?

Those are great questions. With regard to certain morphology types, it is a great question. Right now we do not have data to support using specific biologics based on morphology types or clinical phenotypes. I will say though, as I was referencing in the first part of the talk when we talked about inflammatory versus follicular phenotypes, when I do have patients that have more of a follicular phenotype or you see more comedones and acneiform lesions, I do tend to add on systemic retinoids as adjunctive therapy and I find that sometimes to be helpful.

Otherwise it is difficult to say is this patient going to respond more to an IL-17 or TNF? Often what I tell patients is we just have to give it a try and see how it goes. I do know that there is some evidence to suggest that potentially for young, thin males who have that phenotype, where the buttocks and groin area is involved, there is some evidence that suggests that IL-23 inhibitors may be helpful in that scenario. Again, those are off-label use and difficult to actually get approved.

Then the second question with regard to using Hurley. Yes, agreed. Hurley staging, I do not find it too helpful other than just describing the type and exclusivity of the lesions. It is definitely not associated with severity. I, in my own clinic, I do HS PGA scores. I like that versus the IHS4 because it is very easy to calculate and it is a great way to assess whether or not your patient is improving. For those of you who have never taken a look at it, I would take a look at it. It is really easy to implement. It is just based on how many inflammatory nodules they have, how many draining tunnels they have. It is pretty straightforward.

The other thing I do is I do also track pain scores. That could be really indicative. Again, HS, it ebbs and flows. One day you are fine, one day you are not fine. It is difficult, right? Because we are catching our patients at a moment in time. I also, of course, ask questions to patients at follow-up regarding how many flares have you had since your last visit? Have you gone to the ED, things like that. It can be helpful to assess improvement in clinical improvement.

Okay. Let us see if we can find another question. What is the impact of inflammation on other body systems?

That is a good question. The way I explained HS to my patients is that even though we think of HS as a skin disorder, it is more than that, right? We do know that patients with HS have these comorbidities. We see higher rates of cardiovascular events, heart attack, stroke, pulmonary embolism. I have had a few patients of mine, actually more than a few have these comorbidities. We see metabolic syndrome in these patients, these inflammatory seronegative spondyloarthropathies, things like this.

Even though, yes, we think of this as a skin condition, I explained this is not just a skin condition. This is a systemic inflammatory condition. It is also important to explain that to patients, because when you have a patient that you are having a discussion about potentially like a biologic, for example, I do explain that not only will this help your skin and potentially we have data, for example, from psoriasis patients that going on these meds potentially could also help with systemic inflammation and therefore decrease the risk as it relates to these other comorbidities.

Another question. Okay. With regard to this case that we just discussed, consider her age and social situation and experiences at college. How far is college from HS treatment? Does she need debriefing before or after starting biologic? Can she give her own biologic shots?

Yes. These are really good points. When you have someone that is going away to college, you have to think about all of these questions. If they are going to be giving their own shots, for example, do they have access to a refrigerator? If the patient is severe enough, where you think they are going to need something more than an injectable, something like infliximab, is there an infusion center nearby?

As far as surgery goes, I do have some patients that are surgical candidates and timing is really important. You do not want to do a surgery during spring break right in the middle of the semester. We plan for these things. Having those discussions is really important.

Okay. Real quick, I see a question about, can you talk a little bit about sweating? I often think about Botox and my more mild patients, but maybe I should be thinking in severe patients too?

With regard to Botox, I ask patients if they feel like sweating exacerbates their symptoms. We also do glycopyrrolate as well sometimes. Some patients find this helpful, but I do not offer it to all my patients unless they think this is an exacerbating factor for them.

The other question says, can you talk about goal dose of metformin for HS?

Small Group Discussion on Patient Case 3

Dr. Horissian: Okay. Recapping a little bit. There was a lot of really good discussions, particular to this patient. Again, it is an adolescent pediatric patient. How many options do we have available biologic wise? Does anybody remember? Two. Great. Okay.

Where would she keep that biologic? In a college mini fridge? Who is her roommate? Is she going to take it? Is it safe? What other things is she considering? Maybe she is considering starting birth control now that she is going to college. There is a lot of different factors to take into place. What if she is going out of State? When is she going to see you again? Are you going to have to schedule visits around breaks? There is a whole lot of social factors to consider in addition to just picking the right medicine for her.

Depending on the patient, she may have a different opinion on I want to start birth control and spironolactone or I want to go really hard and start a biologic. Individualizing that to the patient's needs and wants is the best way to do it. Do you guys have any additional points?

Dr. Barnes: One of the things that came up in our group was surgery. What if we just did it now before she left? Maybe that would take care of a lot of what she would have to deal with. We talked through when things are really inflamed if there is not a medication on board. Surgeries can be bigger, more likely to have recurrence. So it is really helpful. We would not do that for an inflamed cyst, right? We would typically try to inject with this ILK[?] or give them some doxy beforehand, so they get the better outcome. That is how I think about HS surgery as well.

Dr. Peña-Robichaux: Going along those lines, I sometimes feel that our pediatric patients, because we are seeing them earlier in their disease, sometimes the parents are pushing for surgery more because they see it as like a quick fix. I always find it a difficult conversation.

Dr. Horissian: I agree. The flip side to that is sometimes people are scared to treat kids. I treat a lot of kids. I love kids. If you see somebody progressing quickly or you see somebody who has severe disease, do not be scared to start them on a biologic. They are approved now. You should have the FDA behind your back to say that it is okay. It goes for that point that the earlier we can start something and change the trajectory of their disease, the better.

Key Takeaways

Okay. Key takeaways of everybody's talks. We have got HS is a systemic inflammatory disease. It has got a lot of comorbidities including metabolic disease, inflammatory bowel disease, inflammatory arthritis. You need to plug them in with a multidisciplinary team.

Diagnosing early before tissue destruction occurs is really helpful. The earlier we can be aggressive about management, potentially the better the patient's long-term outcome will be. I really think of biologics as a disease modifying agent for HS. It is helpful to think of it that way, because HS profoundly impacts their quality of life. It is not something they are just going to have for a year. It is something they are going to have for decades. There is pain, stigma and mental health associated with that.

Educating patients and having them in the decision-making process is critical to coming up with a good plan. There is a lot of new and emerging therapies that are expanding our armamentarium. I am really excited for the future.

Posttest 1

Now we are going to do the post test. This is back to the iPads here. We have got a 28-year-old patient presenting with recurrent painful nodules in the axillae and groin, occasionally drain and recur over time. He is concerned he may have HS. Which of the following clinical presentations is not suggestive of HS?

Looks like most of you got it here. Definitely in the post, we are doing really well with 95% of people getting the correct answer here.

Posttest 1: Rationale

The first episode of an acutely expanding abscess on the lower extremity associated with fevers and chills. HS classically is a recurring disease. By quick definition, we say you have a typical lesion in a typical area happening at least twice in a period of six months. Having a first episode of a lesion that does not fit the description outside of the typical area does not fit, whereas A through C would all fit.

Posttest 2

Okay. Post test two. We have got a 44-year-old man with Hurley stage II, who has got recurring painful nodules and draining lesions in the axilla. Despite previous therapy, his dermatologist explains that dysregulated inflammatory pathways contribute to disease progression and are targets of emerging therapies. Which of the following best explains how IL-17 plays a role in the pathogenesis of HS?

Awesome. This one was a little bit of a stumper here, but we definitely got some improvement from pre to post test.

Posttest 2: Rationale

Just highlighting, HS is a follicular occlusion disease that has rupture triggering IL-17 driven inflammation and that promotes the downstream of IL-17, 23, TNF-alpha and IL-1-beta.

Posttest 3

Moving on to post-test number three. We have got a 38-year-old Black woman with history of hypertension, PCOS, diabetes, lupus and Hurley stage II HS, who presents with nodules, abscesses and tunnels that continue to drain despite topical and systemic antibiotics. She reports significant quality of life impairment, including pain and post-inflammatory hyperpigmentation. Her dermatologist is considering escalation in therapy. Which of the following would be the next step in managing her disease?

Posttest 3: Rationale

Okay, a little bit of a trick question here, but the correct answer is IL-17. You are technically not wrong by picking a TNF-alpha. You could do that, but this patient has a history of lupus. Generally, we try to avoid TNF-alpha inhibitors in patients that have lupus. Since we do have another option of an IL-17 inhibitor on the screen here, that would be a superior option to start the patient on.

Posttest 4

Okay. Post test four. We have got a 36-year-old man visiting the doctor's office for a follow-up. His HS progresses to Hurley stage III disease. He has failed treatment with adalimumab, isotretinoin and infliximab. He is interested in trying one of the recently approved IL-17 inhibitors. While counselling your patient about treatment expectations with an IL-17 inhibitor, which of the following safety considerations would you discuss?

Posttest 4: Rationale

Great. Almost everybody got this one right. Risk of inflammatory bowel disease. The IL-17 inhibitors were tried to use for inflammatory bowel disease years ago, found that it made the disease worse, so they stopped those trials. In most of the IL-17 trials nowadays we actually screen for IBD beforehand and do not include patients with IBD beforehand. Then we look for if a new development of IBD happens during the trial, but generally you would avoid IL-17 inhibitors in patients with inflammatory bowel disease.

Poll 3

Okay. Last poll here. Do you plan to make any changes to your clinical practice based on what you learned in today's program?

Poll 4

Okay. Please take a moment to enter one key change you plan to make in your clinical practice based on this education.

Q&A

We can move on to the Q&A session. I saw one question that I meant to answer while I was talking about medicines, but one question was about TNF inhibitors. What is the highest dose of adalimumab that you can do? There is probably a safety answer to that. I do not know what that is. But I have had patients that have needed double the approved FDA dose. It is sometimes hard to get approved now that we have other options that you can switch to. That is what I have used before. I have not gotten above that. That is usually my max dose.

You can check an adalimumab level and antibody level, which can be helpful in determining if that is the issue. Sometimes people may metabolize it quicker or be bigger and need more medicine. You can look for a drug level and make sure that they are not just eating away at their drug with antibodies and escalate the dose if their drug level is very low.

The question as to what the correct drug level should be is also questionable, and we think it should be higher than that in inflammatory bowel disease when looking at HS patients. So generally above 20.

Dr. Barnes: The other thing that I usually will check for as well is if they notice really good response in the loading period that went down when they went down to like 40 milligrams weekly, then that gives me a hint that they just needed some higher doses, but if they did not notice much during loading, they are not really doing much on 40 and you are going to have to fight tooth and nail with insurance to get the 80 milligrams weekly, it is probably worth it to just try something else. Especially if you are worried about, are they getting enough of the medication, then infliximab is a great option.

A lot of patients like the idea of, wow, this medication, I am getting the amount for my body, which is what I explained to them. We are giving you medicine that is based on your body size, so that it is the right dosage and tends to go over pretty well.

Dr. Lee: Yes, I use 80Q-week often as well, and the HS Foundation has a wonderful prior auth letter that I found super helpful. You can access that and just fill in your patient's information and send that often. That has been really helpful in terms of getting coverage.

Maybe a question for in terms of post deroofing infections and hypergranulation tissue. How do you counsel on wound care to optimize healing?

Dr. Horissian: Everybody that does a deroofing will have a different answer to this slightly. I have seen zero infections in the hundreds and thousands that I have done in our residents do. The infection risk is very low. A granulating HS wound just is less likely to get infected than if you cut out a mole on their back. My usual post-op is Vaseline with a good bandage to hold that Vaseline in place, and then I will add Timolol eye drops and clobetasol ointment if I see a lot of hypergranulation tissue to help prevent that.

Timolol, they are eye drops. Timolol. I forget what the second word to it is, but Timolol eye drops. Timoptic was the brand that we usually use. You do one or two drops depending on the size of the wound in the wound and it helps with hypergranulation tissue.

Dr. Peña-Robichaux: Yes. I typically inject intralesional kenalog into the deroofing site as soon as I am done with the procedure and also have the patient apply clobetasol into the wound with their dressing changes for the first week. I do not know if I have ever gotten hypergranulation.

Same answer. I have never had an infection with deroofings. I wonder if what is going on is if it is just inflammatory drainage, maybe, recurrence potentially.

The other thing too is that I find when patients are on biologics, they actually heal way quicker, less post-op pain. It is just so much less complicated when you have these patients who have very focal tunnels or lesions, and they just want you to just deroof it.

Oftentimes those will have more post-op complications, take longer to heal. I try to encourage some anti-inflammatory treatment if they are going to have a surgical procedure.

Dr. Lee: There is a question on zinc, and if we routinely recommend zinc? Zinc can be helpful. I find it more helpful as an adjunctive therapy or maybe something you can implement for milder HS. Typically for zinc, I will recommend 90 to 100 milligrams of elemental zinc. What is important is when you give zinc, you also have to let your patient know that they should take a little bit of copper, usually at a ratio of like 10:1. It is something easy they can find over the counter. Generally, pretty well tolerated. Sometimes can cause a little bit of GI upset. If it does cause GI upset, you can also recommend it in a gummy form and that can be helpful.

How about laser hair removal? Any thoughts on laser hair removal for HS?

Dr. Horissian: I use laser hair removal a lot. I do not do it as much for like stage III disease, although there are some studies showing it can be helpful, but definitely stage I, 1.5, II. It is really helpful.

In the US, coverage is a big issue for this. There is a lot of efforts to make it an official treatment for that and all that, but I think it can be helpful.

Dr. Peña-Robichaux: Yes, I love using laser hair removal in addition to earlier milder HS in the postoperative setting. When you have patients who have Hurley II or III very widespread involvement of the axillae or groin, they have surgery, they are on a biologic. I often will recommend adjunctive laser hair removal preventatively just in addition, because especially if they are going to see someone in plastics where they have these flaps. So you are still having skin on skin, you are still having follicles around the area. You can go and laser around those areas. It works well.

Dr. Barnes: To the point about cost, because a lot of times we are advocating for it to be covered by insurance. When that is not possible, like I have partnered with some local laser hair removal groups. SEV Laser, for example. I personally went there myself, explained to them what HS looks like, what to expect.

They had the GentleMax that we use at Stanford as well. Safe for darker skin tones because it had the 1064, but then also had Alexandrite. There are things that if you are noticing. A lot of your patients are not getting things covered, then a group on of like six sessions for Brazilian and axillae for only 360 in the Bay area is pretty hard to beat.

Dr. Peña-Robichaux: There is a question about comparing secukinumab and bimekizumab. Secukinumab blocks IL-17A and bimekizumab blocks IL-17A and F. If you look at the data, it does seem that bimekizumab seems to have better efficacy. In the real world, at least from what I have seen, that is true. The way I describe it to my patients is that it is a stronger version of secukinumab.

However, I have seen definitely more side effects associated with it. Specifically, I am seeing a lot of patients with candidal infections, thrush. I have had actually two patients with esophageal involvement had to go to the emergency room. It was really bad. Then these psoriasiform rashes. What is interesting is that these side effects usually occur pretty quickly, usually within the first one to two months.

At least from what I have seen, if you go beyond the loading period of bimekizumab and you are responding and you have not had one of these side effects, generally you are in the clear, but that has just been my experience. I do not know about you guys.

Dr. Horissian: It is really hard to compare the trials because they are designed differently. They are in different time periods, different patient populations. Then what is your comparison? Are you comparing how many reached HiSCR 50 because they might have different placebo rates. Then maybe you are looking at the delta to placebo.

It is really hard. You can look at it one way and come up with one medicine being the best and look at it another way. Some of its number playing. It really depends on the patient. Some people respond better to TNFs, in my opinion, and some people respond better to IL-17s. I cannot figure that out until I give it to them. I have not found the answer to that.

Dr. Peña-Robichaux: Yes, I also think that if you have a patient on secukinumab and you have them on Q two-week dosing, which is the highest dose you can do, and you have had a partial response, at least maybe 50% improvement but they are still having breakthrough. Those are the patients that I feel better about trying something like bimekizumab because, you know they are already responding just how you were talking about earlier. If they have had a partial response to adalimumab, then maybe you check levels, but you would consider increasing the dose. I take that into account as well.

Dr. Barnes: Another important question that we got much earlier is the role of imaging in assessmenwt, especially in the pelvic area. That goes to extend to like perianal area. I am sure all of us here have gotten a lot of patients who manage HS and then you evaluate them and it actually does not seem like it is HS. It looks like it could probably be Crohn's, or like maybe someone has a perianal fistula.

One of the key things that at least I think about is the discharge from HS is usually not as copious as like if someone has a fistula. If it is a higher volume and a little bit like more malodorous, that is definitely a case to just get an MRI. Since a lot of times like these patients might be referred to me for surgery, and the last thing I want to do is get into a fistula.

The other thing is, is if it is particularly close to the perianal verge, I at least will try to just get some imaging because of that higher risk. Then also just getting other history, like we were saying with the comorbidity screening. There are some cases where there is cutaneous Crohn's that it is, if I remember from Bologna or something like 30%. Sometimes people can have cutaneous Crohn's before they even have GI symptoms.

For a lot of patients, they maybe have both. So making sure that you screen for that. Then occasionally, biopsies can be helpful. If I feel like this looks a little bit more like a knife, like fissures from cutaneous Crohn's, the granulomas, as we expect from the pathophysiology of HS should be around hair follicles. If you have noncaseating granulomas that are not associated with the hair follicles, for me, that helps me think a lot more about Crohn's and then make sure that we get GI to do the endoscopy, the colonoscopy, and complete workup.

Dr. Peña-Robichaux: Yes, there are these patients who will just have perianal involvement. If they have no involvement anywhere else, you always want to think about possibly Crohn's. I have had these patients where you go and they see GI and they do the colonoscopy. They do not have Crohn's, they do not have lesions. They will just have these perianal fistulas. I feel like these patients are their own clinical entity. I feel like they are harder to treat.

The other thing I was going to add is besides sending to GI, I have done fecal calprotectin too. I have sent for that because I find that it is not a perfect test. Sometimes if that is really elevated, that could indicate something as well.