Hidradenitis Suppurative Huddle: Better Understand Pathophysiology for a Timely Diagnosis

Dr Amit Garg (Hofstra/Northwell, Northwell Health): I think any of you who has met an HS patient has probably appreciated that they may be some of the most vulnerable patients in our practices for a number of reasons.

One of which is that we have a ways to go in really fully addressing the symptoms and the impact that this disease has on the people it afflicts. However, we have made a lot of really great progress over the past few years in treating this disease. And we will talk a little bit about that today, but it really does start with all of us understanding how the diagnosis is made and how to really comprehensively manage these patients.

So thanks for your investment in that today.

[00:07:30]

Hidradenitis Suppurativa: Overview

Let us talk about HS. Let us start with an overview.

I think many of you will appreciate this is a chronic condition. We consider it to be an inflammatory disease involving the follicular unit. There are bacteria involved. There is a biology, a microbiome, if you will, on the skin and within the skin in patients in HS. However, we do not yet clearly understand what the role of that microbiome is. And there is really no evidence, no strong evidence to date that it is a driver of the disease.

So really this is still an inflammatory disease that results in some pretty characteristic lesions, typically abscesses, inflammatory nodules, tunnels, and then these rope-like scars that appear. And they tend to appear in fairly characteristic areas. They tend to involve intratriginous sites, body folds, such as under the arms, under the breasts, in the groin area, and can involve the genitalia, the perineum, and also the buttocks.

So when you have a combination of these characteristic lesion types occurring in a recurring chronic sort of fashion involving typical areas of the body that we described here, the diagnosis actually becomes fairly readily apparent.

[00:09:12]

Hidradenitis Suppurativa: Epidemiology

We are still trying to understand the true burden of disease in HS. Our prevalence estimates around the world vary quite a bit.

And it is not so much that the disease burden is so different in different parts of the world. I think this range really reflects just how we study prevalence in different ways in different parts of the world. However, in general, I would say that most people believe the disease afflicts up to 1% of patients.

There is probably a range of maybe, let us say 0.5% to 1% is probably our best estimates. That is pretty common, actually, when you think about it. You know, 1 out of every 100 or 200 people on Earth globally may have HS. That is actually a pretty staggering figure.

However, I think the other sort of attributes related to its disease burden are much more well-established. We know that this disease largely afflicts younger adults, so between 18-40 years.

Women are at least twice as commonly affected as are men. And in the United States, we know that HS disproportionately afflicts Black patients. It is less common in kids. We typically see peaks or this disease start to rise in prevalence really after puberty, or I would say even more specifically after adrenarche, which is just before puberty, when we see these hair follicles start to mature. Before that, it is pretty uncommon in kids, except in a very specific subgroup of patients, and that is kids with Down syndrome.

What we have appreciated is that kids with Down syndrome have a very high risk of developing HS. It is probably the strongest risk for a dermatologic disease that exists in patients with Down syndrome. So much so that actually when I am seeing a kid with Downs in my practice, they may be presenting for any complaint related to the skin, but because their risk for HS is so high, I am actually asking them to lift up their arms, and I am peaking in other areas where HS is commonly involved, really just as a screening measure for HS because it is that common among patients with Down syndrome. And we think that has a genetic basis that we are still trying to work through, but that is probably the basis for its strong prevalence in kids with Down syndrome.

[00:12:01]

Patient Perspective: Psychosocial Burden of My HS

Well, we will talk about HS, and Terry and I can tell you all about this disease, but I think one of the things I have appreciated most is that when you hear a patient describe their disease and their journey with this disease, it becomes much more compelling than anything that I could ever say. And so I think, as a level setting, we are going to listen to a patient describe in some ways how the disease has impacted her.

[VIDEO]

Sydney Carter: Hi, everybody. My name is Sydney Carter. I am so excited to be here and to share part of my story with you about living with HS.

So I was diagnosed with HS around 2014, 2015. And at the time I was 17, 18 years old. I had been experiencing HS though for years prior since about age 11 or 12.

Until I was able to get diagnosed with a dermatologist, I was a frequent flier to anywhere that you can. And so even though I went to primary care doctor every single year because I played sports my whole entire life, I never felt comfortable enough to tell him about my HS. And he never asked any questions that made me think I can share that with him.

And so it was not until I was diagnosed by a dermatologist that I realized that dermatology correlates to skin. And so it took years after getting diagnosed to go back to a dermatologist just because I felt like there was such a lack of treatment options, a lack of bedside manner, and options that were given to me at that point.

So I just did not take care of my HS after that. And it became a huge burden to me mentally, physically, socially, not only my friends, but intimately. And so it has been a huge journey to get to where I am now and unburdening all of those psychosocial things that happen to you as an HS patient.

[00:14:15]

Hidradenitis Suppurativa: Pathophysiology

 Dr Garg: Okay. So, quite a bit to actually unpack in a lot of what our patient described. And certainly, I think a lot of what she said will resonate with your own experiences in speaking with patients.

So with that as a backdrop, let us dive into a little bit about how HS happens, its pathophysiology. What I will say is that we are still trying to understand the pathomechanisms of this disease, and I think we are not quite there yet. And that is one of the reasons we do not yet have a cure, or at least a treatment that fully addresses this disease and all the ways that it manifests.

However, I do think we have come a long way in understanding what is going on in the skin. So, as I mentioned, this really is an inflammatory disease that really involves the follicular unit. Through various influences, follicles in these intertriginous areas become occluded, essentially. And that occlusion eventually results in a disruption of the follicular epithelium and ultimately recruitment of a whole host of types of inflammatory cells and cytokines that ultimately leads to the manifestation of the disease, which we described as inflammatory nodules, abscesses, and even tunneling, which eventuates in scarring.

[00:15:50]

Hidradenitis Suppurativa: Immune Pathways

Well, what are the inflammatory cells we see? There is really a whole host. I think when we look at expression studies in tissue of HS lesions, it is really all over the map, but some of the things that really stand out are cytokines, overexpression of TNF-alpha, IL-1-beta, IL-17, and that is really the basis then for drug development programs around trying to address the inflammation in HS lesions and by way of that, the symptoms that the disease causes.

[00:16:30]

Role of IL-17 in the Pathophysiology of HS

IL-17 has risen as a particular interest because we now have 2 new drugs that specifically target the IL-17 pathway that have been approved in HS. IL-17 has a number of roles in inflammation in the skin, and in particular, HS. We know that it is involved in recruiting in a number of different types of inflammatory cells, monocytes, and particularly neutrophils, with HS being this suppurating disease, and also recruits in Th17 helper cells and other myeloid cells that again help promote that feedback of driving the IL-17 response. And so with this as an overexpressed cytokine, in HS lesions, it became a target of interest. And indeed, we will go over the data in a little bit, but when we target IL-17, we see very good efficacy in managing the disease.

[00:17:38]

Clinical Phenotypes of HS

Not all HS patients have the same exact phenotype or presentation, if you will. We do see some differences, and we are doing a lot of work to try to sort out what these different phenotypes are, how each phenotype behaves, what the natural course of disease may be for individual phenotypes, and certainly trying to understand response to treatment for individual phenotypes. Ideally, we get to the point where we can say, well, this is a particular type of phenotype that this patient has, and we know that this particular target of treatment works best for this phenotype.

We are early in our evolution of that concept, but you can see here listed a few phenotypes that have been sort of identified or at least distinguished. The most common one is the one that I am describing, where you get the inflammatory lesions that I described in intertriginous areas. The follicular phenotype, more follicular-based papules and inflammatory nodules. You get significant involvement of the trunk, with some involvement in the intertriginous areas, but it is more of like a truncal process. And even a phenotype that really heavily involves the hips and the girdle area.

[00:19:10]

Clinical Presentation of HS

So we did discuss this, but I do think it warrants just some emphasis here because the diagnosis really does rest on the clinical presentation. When you have chronically recurring inflammatory lesions, such as inflammatory nodules, abscesses, tunneling in the skin, presence of rope-like scarring, which is the ensuing damage, and other lesions that are characteristic in HS, such as comedones, or even these double comedones, or triple comedones, we call them, occurring in classic areas, such as in the axilla, under the breasts, in the groin, the perineum, the buttock, that really does strongly suggest a presentation for HS.

And this is important because 1 of the things that we have appreciated in the medical community at large, not necessarily just within dermatology, but there is generally low awareness of this disease. Some clinicians have not even heard of the words, hidradenitis suppurativa, so we cannot expect, necessarily, that they would readily be able to diagnose this condition when it presents.

And so, it is not so surprising that an HS patient who does not yet have a diagnosis has a huge flare in the axilla with an abscess, shows up to the ED, that that patient is diagnosed with an abscess, and managed with an abscess as an abscess, rather than a diagnosis of HS, and really optimizing treatment here towards a chronic inflammatory disease, such as HS, rather than an infection, such as abscess.

So this clinical presentation, I think, is important to sort of lock away. However, more on diagnosis, I am going to actually hand it over to my colleague, Terry, who has going to take us through, um, diagnosing HS.

[00:21:19]

Diagnosing HS

Terry Faleye (Dermsurgery Associates): Thank you,  Dr Garg. So, just like was spoken before, HS is 1 of those things that it is so confounding that when you think about, yes, understanding the clinical presentation, and when it presents itself, but I think even more so as providers, as clinicians, it is so important about definitely being able to diagnose and make the diagnosis. It is so sad, many times you have these patients come in, and yes, they have had HS for 10, sometimes 15 years, and the thought is that, wow, it is not a case where that patient just noticed it for the first time.

It is also the fact that, you know what, this patient has probably likely gone to multiple ERs, they have gone to multiple urgent cares, they have been to multiple, even PCPs, wanting a diagnosis or even understanding so far as what is going on. And so, it sometimes behooves you when they come in, and they look frustrated, they look upset, they look angry, and rightfully so.

So, it is super important, definitely, I think, number 1 is definitely being able to, 1, clinically recognize HS when it is presenting, and recognizing those paronychials and recognizing the papules and all the areas that we talked about, the axilla, the gluteal area, so far as the inframammary areas as well, too, that tend to be involved.

However, at the same time, I think it also bears down on us having time to actually listen to our patients, and actually conducting a proper physical examination. You have to have them, unfortunately, sometimes take off their clothing and things like that, and sometimes that is not very easy for HS patients. It is because they already have this feeling of shame, of the odor, and just the confounding components to the disease really kind of make it a very hard visit.

However, I think more than anything is recognizing that it has to be confirmed clinically, and recognizing that the diagnostic criteria is, 1, where the areas of skin involvement are, where they lie. At the same time, these lesions, they are inflamed, these nodules, these abscesses, especially when a patient comes in and tells you, you know what, I have gone to the ER, you know, last 5 years, and I just go in, they drain it, and they make it better. Sometimes that is why they are coming to you.

And so when you begin to recognize where, where the locations are, it then drives that understanding of what is going on. And also the, the chronicity of it. We recognize that many times that these patients have been told that they need to clean more, especially from when they were in adolescence when this began.

So sometimes there is that stigma that goes along with it, but the chronicity of it is what a lot of times what drives these patients into our offices, and wanting to know more, like what is going on?

[00:23:54]

HS Presents Differently Depending on Skin Tone

So it is also recognizing, especially with HS, that the presentation can look very different when you are looking at skin of color. A lot of times, I feel like a lot of my skin of color patients, the severity is definitely much more increased. But then at the same time too, many times my skin of color patients sometimes feel like they have truly been going to providers, and they are not getting any answers, or any idea of what is going on. So sometimes that frustration is there. So, it is recognizing that they tend to be definitely disproportionately affected, but it is also recognizing that it can clinically present different.

So in your Caucasian patients where you definitely have those fluctuant nodules, and they are erythematous, and they are red, and you see the papules and pustules, when on darker skin, it tends to be a lot more violaceous, a lot more dark and dusky. And so sometimes it is a case where they themselves, you will notice if a patient's in a room, sometimes they will not even sit down because if it is in the gluteal area, the first presentation will be like, it hurts. I am not even going to sit down right now. I am just going to stand for most of this visit, or you can see that they are brought to the side, they are more leaning to 1 side of their buttock and not the other.

So you just basically begin to assess, there tends to be a lot more intense hyperpigmentation that is at play, and definitely is recognizing that sometimes a lot of times we think that when we see hyperpigmentation, then it is not really active. That is not the case, especially when we are looking at skin of color. A lot of times, erythema in itself, it is not in the absence of inflammation. Inflammation is still very much present, despite the fact it does not look pink or by textbook characteristics, what we are wanting or what we are used to looking at.

[00:25:39]

Risk Factors for Developing HS

So it is also recognizing the risk factors, because obviously, that is the next question patients have. They are just like, okay, you have now told them what it is. And now they are just like, well, how did I get this? However, it is also recognizing that we have to let them know that there are risk factors at play.

I remember years ago, it is a case where I used to be in infectious disease. And I can tell you that it is not the case. I was under the understanding before dermatology that this was more of a bacterial infection because that is what I was taught or what I was alluded to thinking. And so, but recognizing that, just like  Dr Garg said, there are definitely multiple pro-inflammatory cytokines at work. And knowing that it is not just a bacterial disease, it is a case where it is definitely so far as inflammatory, but it is also recognizing there is a genetic predisposition for these patients.

A lot of times there tend to be first-degree relatives that do have the disease as well too. Or sometimes you can have patients that come in that may be adopted or whatnot, and they do not even know so far as their history or family history. So sometimes you have to do a little bit more digging in that regard.

However, lifestyle does play a big role as well too. We definitely know that when we have patients that these patients in itself overarching with a lot of the inflammatory syndromes, when metabolic syndrome comes into play, and we have patients who are overweight with high BMIs, we definitely know that because of the skin friction and sweating production, and not only that, a lot of times their disease characteristic tends to be a lot more severe in these patients. So we tend to notice that sometimes when these patients lose a little bit of weight or get weight under control, sometimes disease does improve.

However, there is also clinical data that definitely supports the aspect of smoking. Definitely, it is a case where 70-90% of patients with HS, a lot of times they tend to be sometimes smokers, not always. However, it is associated with epidermal so far as thickening, and as well as impaired, you know, pathogens so far as killing those neutrophils as well too. So it is very important if we can counsel our patients, letting them know that, if you do stop smoking, your disease progression may definitely improve. Not to say that it is going to completely go away. So we want to definitely temper expectations, but we want to let them know that definitely factors that are definitely inhibiting so far as improvement.

And also, you know, friction from tight clothing. And at the same time, a lot of times we have a lot of these females, a lot of times I have a lot of young girls that come in or that they are in high school, and they are starting to develop so far as whether it be late puberty, or whether you have some that are in middle school, you know, it is a case where it is recognizing that a lot of times menstrual cycles, a lot of times you may see that after they start their menstrual, that a lot of times some of these symptomologies may start to come about, or pregnancy or menopause. So it is taking all those risk factors into consideration.

[00:28:28]

Hurley Staging System

So we know that with HS, it is a case there is a staging system at play. And I think a lot of times, when we are documenting so far as in our, you know, EMRs, it is very important that we know that definitely what we are looking at, and what stage we are at, because that in turn lets us know how we need to progress, especially in regards to treatment, because definitely our idea and understanding of HS has definitely evolved. And I think it is awesome that there are now multiple treatment options that are flooding into the landscape, and many more that are coming into the space for a much needed so far as disease.

However, when we are looking at Stage I, it tends to be more abscess so far as formation. It is not the evidence so far as tunneling that is there, but even sometimes not very characterized by any scarring. However, a lot of times these patients come in saying that, hey, I have a little boil, can you just drain it for me, and I will get on my way. And that is the presentation that a lot of times these urgent cares kind of come about.

Then we talk about Stage II, when it tends to be a little bit more recurrent, having recurrency, we have skin tunnels, and at the same time, scarring as well, too, starting to take place. And a lot of times I feel like by the time we see them in derm, I feel like a lot of times we have got to the place of Stage II and Stage III, unfortunately. However, by Stage III, it is much more diffuse, it is interconnected. That is when a lot of times you may push on 1 area, and it is draining from another site. And that is from itself, just from the tunneling and abscess formation that is happened. And it tends to be super unfortunate because these patients are just in pain. It is definitely such an unfortunate disease process.

[00:30:04]

Other Staging Systems

However, it is recognizing also the different staging systems that are at play. When we are talking about clinical data, and even looking at the clinical research data from all the different drugs that are on the market, a lot of times we see these things when it talks about HiSCR50, HiSCR75, and HiSCR90. And I always say that from a patient's standpoint, they do not know what a HiSCR is, but they are wanting definitely improvement.

However, just for our recollection, it is knowing that, that means that it is at least a 50% or 75% or 90% so far reduction in the total inflammatory lesions that are there, as well as abscess and nodule counts. However, no increases in draining fistulas or anything at baseline.

Then IHS4 is basically an international hidradenitis suppurativa so far as scoring system. And that just takes into consideration the number of nodules, abscesses, and draining tunnels. And with nodules, you multiply it by 1. For abscesses, you multiply it by 2. And tunnels, you multiply it by 4 and get so far as your scoring system.

And then the other is that the HISTORIC COS, and that in itself, I think is really important because I think that taking into consideration a patient's introspective understanding of their own disease, but how they look at themselves is super important. And recognizing how that patient quantifies their pain, how they quantify their physical signs and symptoms, even their quality of life because that is a big portion of it. You can have a patient that you have put on therapy, and in your mind, you are just like, well, I improved the drainage and different things like that. However, you know what? Holistically, we are looking at the entire patient.

If it is a case where they still feel like their quality of life is still super impacted, then we still have a long ways to go. However, it really looks like the global assessment as well as the progression of the disease course as well too.

[00:31:48]

Early HS Diagnosis Is Critical

So 1 thing that is very critical is delayed diagnosis. It is so critical that we are able to recognize this disease early. And I think that what we know overall is that if we can detect this early, we can educate our patients early. I truly believe that we have truly altered the disease course for this patient by far.

Does not mean that we curbed them, in which they do not have HS anymore. However, I think a lot of times I think that it reverses the fact of this patient having to go through scarring. The fact that this patient has to go through periods of life where they feel like they have to hide from family members or not go to a wedding or not go to functions just because they are afraid that they are going to drain all over their clothing.

I mean, I think that that is 1 of the big things that we are able to diagnose early. It is such a huge benefit. Obviously, recognizing the comorbidities at play and honestly educating our patients of those comorbidities because they just do not know.

At the same time, surgical intervention. We know this is a disease that many times is truly multi-modal that we are definitely utilizing, you know, whether it be medical management as well as surgical management, whether it be deroofing and all those different modalities. It is not just 1 thing.

However, I think that when we are able to intervene early, I think that may sometimes maybe delay what we are doing in the severity cases, and also the patient burden and also utilizing of high cost medical care. You think about you are going to urgent care, and you have now run up a bill that you know, what if you knew that you had HS 5 years ago, you may have you may have chosen to go a different route. So super important.

[00:33:32]

Symptom and Psychological Burden With HS

So also recognizing the psychological burden of the disease is just recognizing overall that there is such a huge stigma, the body image that is associated with it, as well as depression. Depression is real. Many times I say that these patients, I feel like if you have ever watched the movie Inside Out, I always say that all those emotions that come about, you know, the anger, the anxiety, the depression, all those things, you think about it, it definitely takes a big toll.

So when you really look at seeing that there is a meta analysis that indicated those with HS were at increased risk of actually committing so far as suicide, and even though that so far as the adjusted odds were much higher so far as with depression, but you definitely see the prevalence, especially when the suicidal rates with these patients as well to recognizing that disability, you know, those patients that it has impacted their lives in which they cannot go to work, you know, they are in pain, and then they cannot function or even having hospital visits and different things like that.

I think overarching is recognizing that the mental health component of disease is real and being able to address it early is so important.

[00:34:40]

Negative QoL Associated With HS Exceeds Other Chronic Inflammatory Dermatoses

And then just this overview just really just talks about like to talk about that quality of life. That I think we talk about quality of life, we talk about it when we are talking about psoriasis and atopic derm and as well as urticaria as well, too. However, with HS, you do definitely recognize, and I think that we can all agree that definitely these patients suffer to a much higher degree or how they view themselves and how this disease affects them, definitely greatly exceeds those patients and other so far as other inflammatory disease dermatoses.

And honestly, sometimes there is the overlapping arch. You definitely sometimes can have those patients who have HS and psoriasis or overlapping so far as disease. So sometimes we are not even unpacking that, those patients who have compounding multiple inflammatory so far as conditions on board.

This just took into consideration, it was a multicenter registered study that looked at those patients and those that had started or modified so far as systemic disease treatment. And this is really recognizing that 43% of those so far as with HS and vs those in chronic urticaria because they missed work because it impacted their lives much higher so far as in these patients with HS. So overall, we definitely have ways to go, but it is recognizing that this definitely affects our patients' lives.

So I am going to go ahead and turn it turn it over.

Martha Sikes: Both  Dr Garg and Terry, I mean, you are bringing up incredible points. I mean, these people come in, they are frustrated, they have been dealing with these lesions. They are not in fun areas, right? They are in areas that are very uncomfortable and sensitive, and it can be quite burdensome here.

[00:36:24]

Case Study 1: John, 32 Yr of Age

So let us take a look at John. John is a 32-year-old male who presents with a history of inflammatory lesions in his perianal area and medial thighs within the past ten years. Area's involvement previously improved with episodic antibiotic treatment. He visited the urgent care and emergency department multiple times to seek medical attention and was never prescribed anything to manage his pain. John reports significant emotional impact, as well as feelings of embarrassment and self-blame.

So I will open it up to our faculty. What factors would you consider when confirming the HS diagnosis for John?

 Dr Garg: Yes, so I think it is amazing, right? This is a case and without even seeing a single picture, you can get a sense that HS may be at play here. So even taking a really good history can help with this.

So, inflammatory lesions, the patient will probably call these boils, for example, or lumps and bumps, right? However, you get the idea that they are these inflammatory lesions involving pretty typical areas. The perineum, the buttock, the medial thighs or the groin folds occurring over and over again over a ten-year period.

I mean, people can get abscesses, but it might happen once, maybe twice, and not even typically in the same area. However, you have got here a ten-year history of these similar lesions occurring in those characteristic areas over and over again over years in those same areas. So I think there is a lot here that really helps you get a sense that HS is a high likelihood.

Terry Faleye: Yes, I definitely agree. I think him just saying that he has been to multiple urgent cares and ERs in itself is just like a red flag there, you know, for ten years. Because you definitely recognize that means John started having this in his 20s. However, he has a frustrated young man at this point in time. So definitely, it gets your well-housed thinking, without him even taking off his clothes that something is going on.

Martha Sikes: Yes, and it highlights what you were saying just a little bit ago, Terry, with the cost that is involved with this too. Every time you go into the urgent care or emergency room, and you are having IND to these lesions, that is a lot of expense, and it is not really targeting what the real problem is in HS. And then the second part of this is he was never prescribed anything to manage his pain. I mean, that is something that is inherent to these patients. They are very uncomfortable.

[00:39:13]

Case Study 2: Kylie, 32 Yr of Age

All right. So what about Kylie? Let us look at Kylie. She has 32 as well, but she has a low BMI, and she complains of recurring lesions in her armpits, behind her neck and around her groin. She works at a store and says, I cannot lift my arm to put things on the shelf. It made me quit my job.

Kylie's been managing her condition via obsessive hygiene and cleanliness practices. She has not sought any treatment until now, and does not report any significant medical history. Clinical examination showed multiple lesions and abscesses with skin tunnels and scarring. Have you seen this before?

 Dr Garg: Yes, you know, absolutely. We see this type of patient all the time. And I think, this case study of Kylie makes me think about a couple of important concepts that we should all be thinking about when we are working with our HS patients.

One is symptom burden and impact. She cannot really even use her arms as effectively. She had to quit her job. So many HS patients will describe, I cannot study. I cannot go to school. I cannot stay in school. I cannot get a job. I cannot keep a job. I cannot advance in a job. All in my 18, 20, 30-year-old period, which is a time when we are all trying to do these things. So it is a high burden, high impact in such a fundamentally critical time in life.

And then the other concept here is stigma. You know, we talked a little bit about BMI as being a risk factor. And I think there is enough data now to suggest that it is a risk factor, but it is not the only one.

Terry Faleye: Correct.

 Dr Garg: In fact, there are many. And in this case, Kylie has a low BMI. So before I even bring up things like weight management and smoking cessation with patients, I often really just try to make sure I have a very strong therapeutic relationship with my patients. Because before they got to us, they have got ten years of being bounced around, ten years of being blamed. It is your hygiene. It is your weight. It is because you smoke. None of which is fair. And frankly, none of which may even be true.

And so, before I even bring up things like weight management, smoking cessation, other lifestyle issues, just make sure I have got a good trusting relationship with the patient. And then really what I say about it is the truth is we do not know that they are strongly related or that they were related in your case. And we also do not know that if you were to change things that your HS would substantially change.

You should manage your weight. You should stop smoking because it is something you want to do for your overall health. We know that it is important for your overall health. Will it change your HS? We can hope. And if that is extra motivation, let us use it.

So just a couple of things as this case has evoked for me in terms of what I often have conversations around with my own patients.

Terry Faleye: No, so true. I think that 1 thing I took from you,  Dr Garg, was the fact of cannot. And I was just like, I never heard cannot. And you think about it, you are just like, you know, I cannot do this. I cannot do that. I cannot do that.

And just the reality of just like, wow, so much impairment, because at this stage in your life, you are just like you are used to telling your kids you can. You know, go out and do this. You can do that. You know, conquer the world. You can.

And man, all the limitations of this disease in itself and how much it impacts Kylie to the fact that she has just like, yes, I cannot work. I cannot lift up my arm. I cannot pay for this. I cannot. It is just like, and the burden of the disease is just so real.

And not only that, just recognizing her clinical exam, just the fact of multiple lesions and abscesses with tunnels and scarring. It just speaks to the fact of the chronicity of this disease and how advanced, because then you are looking at the fact of just like, wow, she potentially obviously is no longer early Stage I. You know, we are now looking at someone who has potentially more early Stage III, or maybe kind of in between.

And it just saddens you because you are just like, wow, she progressed to a place where she cannot. If she would have known maybe she would have been doing something when she was the "I can. I could do something".

[00:46:08]

Faculty Discussion

What are some questions you would ask this patient?

 Dr Garg: Yes, I think for me, I try to keep it simple because I think you can get really kind of caught up in the weeds and trying to distinguish II from III. But I actually think the most important distinction is distinguishing I from any other, because that helps you decide on how to manage the patient. And so for me, if I see just either 1 tunnel or 1 rope-like scar, I know that that patient is at least II. And that is all I really need to know to decide, okay, we have to think about some advancement in treatment because you have already got presence of tunneling and scarring, and we know that this disease is chronic and usually progressive, meaning things are going to get worse.

And it is really hard to control symptoms or modify disease when you have patients who are very severe at III, and our best drugs do not really work as well at that point. So the goal is to try to identify patients who are at the earliest of II, and get them on the best treatments that we have. And so for me, I think that is really the relevance here.

If you see even just 1 tunnel or 1 rope-like scar, that puts them at least II, and you got to manage them in a different way.

Terry Faleye: Definitely, I agree. I mean, I think it is just catching these patients early and then at the same time definitely being, definitely aggressive in how we manage these patients. Because sometimes in some areas, we may take the approach of mild. Okay, well, mild, I will just give you something mild. However, the reality is that there are so many factors that are kind of going with this disease, you could definitely have someone that is mild and progress quickly to something else more. So definitely how we approach these patients, just like  Dr Garg said, I think it is more knowing, okay, where am I dealing with 1, or am I dealing with II and III? And that way I know how to then approach this patient properly.

Martha Sikes: Yes, how aggressive to be.

Terry Faleye: Yes.

 Dr Garg: Our best treatments that we have to date based on the evidence are the biologics. The biologics are indicated for moderate-to-severe disease. And it begs the question, what is moderate-to-severe disease for us in practice, separate from clinical trials? And I think that, you know, you can make a very clear argument that Hurley II, meaning 1 tunnel and/or 1 scar, puts them at Hurley II, and that is certainly moderate-to-severe disease.

Terry Faleye: Yes.

 Dr Garg: You can even argue that even Hurley I patients can reach moderate-to-severe status. And let me tell you why. The inclusion criteria for a clinical trial is 3-5 inflammatory lesions.

That means you could have 3-5 nodules and/or abscesses and be considered moderate-to-severe. So if you have 3-5 inflammatory lesions, even without a tunnel or a scar, you can be considered moderate-to-severe, at least by definition for inclusion in a clinical trial. So, I would encourage this group to think broadly about what moderate-to-severe disease means.

And it can be, certainly if you have 1 tunnel or scar, that is moderate-to-severe. If you have even 3-5 inflammatory nodules and/or abscesses, even without a tunnel or scar, that is moderate-to-severe disease. And that is a Hurley I patient, actually, by definition.

And if you think about how we approach inflammatory disease overall, right, in psoriasis, we also take into consideration not just body surface area, but impact. So you could have small surface area, but if it is involving your palms, your soles, your genitalia, your scalp, those are high-impact areas, and sometimes we advance treatment because the impact of the disease is so great for patients.

So there are a lot of ways to think about what is moderate-to-severe disease in HS for clinical practice, but I think the idea is to identify these patients early, think about their impact, think about what the physical signs of the disease are, but also recognize that this is a chronic and progressive disease. And if you do not modify the disease course in some way now, it is impossible to do it when they are really advanced, at least with the therapies that are available today.

Terry Faleye: Yes, definitely. I would also put 1 more challenge too, just like  Dr Garg said, I think that when we are looking at mild, moderate, and severe, it is definitely taking into consideration the patient's experience. I always sit back and say, if I am looking at a patient and yes, they look like they are mild disease, but you know what, but if I grade that patient, that patient defines their disease as severe, they are just like, no, this is impacting my day-to-day, even when you are looking at just a few abscesses, then is it really just mild? You know, one would beg to differ. So, I think at that moment, really take into consideration, yes, obviously what we are clinically looking at, but definitely the patient's experience, I think definitely drives home a lot of how we even manage as well.