Lupus Unlocked- Cutaneous LE - Tuesday Night Rheumatology Save

Okay, welcome everyone. I'm glad you're all here at Tuesday Night Rheumatology. Episode of Tuesday Night Rheumatology is devoted to cutaneous lupus erythematosus. This is part of our lupus campaign month, lupus unlocked, you have the keys to mastery. This whole campaign month, this webinar is sponsored by Aurinia and we thank them for that.

Tonight, I've got a great panel and I'm just delighted to have four esteemed dermatologists who are experts in what we see and do. And it's really important that they're here to take your questions and to discuss some of the issues that we are gonna put in front of them. Our panel includes Doctor. Victoria Worth from the University of Pennsylvania, where she is professor of dermatology and medicine. Doctor.

Matilda Nicholas from Duke University Medical Center, where she's a professor of dermatology. Doctor. Anthony Fernandez from the Cleveland Clinic, who I was with this weekend at a great meeting at the Cleveland Clinic, Director of Medical Derm and Assistant Professor in the department there. And Doctor. Christopher Richards from the University of Rochester, associate professor of Durham and Rheum.

I'm really confused by Christopher Richardson at the University of Rochester must get confused with Christopher Richland at the University of Rochester all the time. Is that true?

That's true. So I actually did my graduate work well within Yaki Sands, who was at the time Chief of Rheumatology, and Chris was there and I would get his mail all the time, and I still do, and I kind of feel honored, so anyone in rheumatology would probably know Doctor. Richland, and so to get confused with him even in the mail room is an honor.

It's a good thing. Right? So alright. So the format of this is I want all of you who are watching at home to put your questions in the q and a box and not the chat box. That's really, really important.

And so it's really something that we'll be watching during the session. We're going to use as a script a PowerPoint slide set that I prepared for this that will include some of the questions that we pose to you in our weekly survey this week. So let's see, there we go. From a start with PowerPoint. So here we go.

I hope you can hear me. I want you to know that every Tuesday night, we'll do Tuesday night rheumatology. Last week, was Journal Club on lupus nephritis. It was great. Tonight, we have a panel of great experts in medical dermatology, rheumatologists and dermatologists alike.

And that's on our program tonight. We're also going to tonight sort of adhere to a script that in discussion with our experts that we wanted to cover the topics of the diagnosis of CLE, including how we use labs for serologies in patients who we have. Measuring outcomes both in our practices and also in clinical trials. And then end with a discussion of treatment of CLE. So we sent out a survey On Sunday night, we sent it out Monday morning.

In less than twenty four hours, we had 200 responses. So, includes about half who are from The United States. As you can see on the right, eighty seven percent are adult rheumatologists, nine percent are advanced practice providers. And we thank all of you for your input. I always look at these data and look at whether it's a difference between the international community and the Americans.

And on these questions I'm gonna show you, there's really no difference. Okay? So I'm gonna show you the results of The US community. We're gonna begin with a discussion of diagnosis and diagnosis by lab. The first issue was, who diagnosis cutaneous lupus?

You thought rheumatologists thought that dermatologists was diagnosed two thirds. I don't know that I agree with that. We're gonna get to that in a subsequent slide, but I wanna ask our panel to discuss these next two questions. What labs do you order in discoid or SCLE patients? And sixty one percent of you said we do full serology, twenty six percent just an ANA, a minority less than nine percent are doing SSA and SSB, but really ninety one plus percent of you are doing some labs in patients with CLE only.

The question is, is that right? Does our panel want to address that? Doctor. Wirth, I think you had a comment on that, the note you sent to me.

Sure, I think I would of would back it up a little bit just to talk about who makes the diagnosis, because I think that lupus is so heterogeneous in how it presents, but if it's truly just cutaneous lupus and presenting on the skin, I do believe a lot of those patients end up seeing dermatologists. They go to a primary and they often end up referred to a dermatologist. And so I don't disagree with the pie chart there. In terms of serologies, I mean, I think if we know a patient has cutaneous lupus, I think we wanna make sure that, in particular, I wanna make sure that they don't have renal disease. So, and I'll check an ANA, but that's not gonna tell me if they have systemic disease or not, but I will check urinalysis.

And if they're photosensitive, I might check an SSA and SSB. And if they have an ANA, I'll check a double stranded DNA because if it's elevated, I'm probably gonna follow those patients a little more carefully, even if at the time we see them, they don't have proteinuria. So those are sort of my initial approach, but obviously there are many other labs that we could consider for individual patients.

My question, I guess, and I'll throw this to Chris Richardson, do you need labs to diagnose CLE or is it pretty much a physical exam and history diagnosis?

Yeah, I would say it's mostly a physical exam and maybe some history. I find an anti Rho antibody helpful when I'm considering SCLE, probably the most helpful of any of the labs as far as diagnosing cutaneous lupus. But I agree with Vicki, it's good to do a little workup to see if they have systemic disease. I think the UA, which is not represented here in the graph, right, it's full serologies, that may be the most important one for me to find out if they have nephritis, because a lot of the other things they can tell me about, right? Do they have joint pain, for example?

But the kidney disease is silent, so I think that has to be looked into specifically. And I would say probably the one that many dermatologists forget to do, maybe not those of us who do a lot of room derm, but one I bet most of the rheumatologists are doing pretty routinely.

I guess the other question here on diagnosis is, should we be referring people for biopsy for diagnosis? Tony, you wanna address that?

Sure. So I don't think every patient needs biopsy. I think there are certain clinical scenarios and clinical presentations where it's pretty obvious that the patient has cutaneous lupus and what immediately comes to mind is acute lupus in the setting of SLE and your classic butterfly rash. However, I do think a biopsy is valuable and I do like to get biopsies on most of my patients. I think there's something that is nice about having objective information not only at the time you make the diagnosis but from that point forward in the patient's medical history so that any clinician who sees that patient does have more evidence than just seeing a photograph or having the patient tell them that they had cutaneous involvement.

You have that histopathology report that shows you that information that confirms or supports a diagnosis of cutaneous lupus.

Does anybody else have a pearl on diagnosis of CLE that they think that the rooms need to know? I mean, the one thing I'll say is I think what I see a

lot and maybe the other panelists see is that clinicians other than dermatologists, not just rheumatologists but all clinicians who see these patients when they have a diagnosis of lupus there's a tendency to want to attribute just about any rash that occurs as being cutaneous lupus. And I think there are plenty of rheumatologists who are good at doing a clinical exam and knowing what is cutaneous lupus or not. But even if you're not, I think cutaneous lupus there are only so many subtypes and I think there are specific features about most of those subtypes that it doesn't take that long to learn and I think that can if you do take the time to really study the different subtypes I think you can get very good over a short period of time at recognizing a lot of times what is cutaneous lupus and what is not. Okay.

And I might add.

Nikki, go ahead first and then we'll to Matilda.

Yeah, I might add that there are mimickers of lupus and the biopsy is only so good as being able to do what we call clinical path correlation. And in particular, a biopsy with interface dermatitis, as you often reported out as consistent with lupus, with the idea being that lupus is, more common than dermatomyositis, which is another disease that can give you interface dermatitis on biopsy. And so I have to say that I see a lot of dermatomyositis patients who come in with a diagnosis of lupus and they don't have lupus. So in addition to learning the morphology, it needs to look for the differences between dermatomyositis and lupus. Matilda, you're on.

That was literally exactly what I was going to say.

I was

going to say Vicky has published extensively on this, but I feel that that's a really, really common thing. And the only other little pearl I'll say is that, you know, when I get a referral for lupus patient that had a drug rash in response to hydroxychloroquine, there's like very high odds that that patient actually has dermatomyositis. So just reminding the rheumatologists that up to thirty percent of patients with lupus can have a drug eruption in response to hydroxychloroquine, I'm sorry, not with lupus, just rhomyositis, which is really unusual in lupus patients, but can happen.

Excellent. Admit a couple of

things maybe to Once you get us started, there may not be any stopping this.

Yeah, that's good, good.

So I just got a referral this week, which is pretty common, from a rheumatologist, which is, Is this acute cutaneous lupus or rosacea? That was the clinical question. And I can imagine that my rheumatology colleagues, which are great, often get this patient, which all of the rheumatologists have seen, they have an ANA of one to 80 and they have a rash on their face, right? And it really does matter if that's cutaneous lupus or not. So they send them my way, because I've got a good relationship with them, to talk about that.

But I think a lot of those referrals probably could be avoided really from our perspective, at least my perspective, I think it's shared by many, the malar rash of acute cutaneous lupus is a sign or symptom of systemic disease, active systemic disease, and if someone comes in and they just have a malar rash and they don't have anything else going on as far as, you know, systemic lupus, it's not systemic lupus. And so, just keeping that in mind that the malar rash is a manifestation of active or flaring systemic disease is really important. Just asking some questions like, does it flare in the sun? Well, that's not going to help you much because rosacea flares in the sun too, right? But what about caffeine, alcohol, those kinds of things?

Oh yeah, every time I have a drink it really flares up. Some of those things can point you towards rosacea, as well as obvious telangiectasias on the skin or papules and pustules, those are things that are less common in acute cutaneous lupus. So I think those are things that could really help the rheumatologist turn that patient around back to the primary care doc pretty quickly that I find really helpful. So the other comment I was going to make, which is unrelated, and I guess I'm curious what others on the panel might say, but I find a DIF not terribly useful most of the time for diagnosing cutaneous lupus. I think the H and E of the interface dermatitis that we've talked about is just or more helpful, so I'm not I think I used to do a couple of biopsies in the past, but I'm finding I'm not really doing a direct immunofluorescence DIF biopsy very often to help me figure out if something is lupus, but I don't know if the others on the panel have a different

Yeah

and I totally agree because there can be false positives people with photosensitivity or who've been in the sun and sun exposed skin who don't have lupus can have a positive antibodies in the skin at the dermal epidermal junction. So it's not a very specific test and usually not so helpful.

I agree as well and in fact we are getting ready to really look at our history of this and try to really determine does DIF patterns do they really make a difference in our ability to determine if somebody has cutaneous lupus or not? I think just over the years the serologic panels and other aspects of evaluating patients with lupus have just gotten so good that the need for direct immunofluorescence has just kind of fallen by the wayside and that's okay. But I mean I think in terms of saving healthcare dollars I think it is important that we do not think that DIF really plays an important role and to share that.

Yeah, I mean, one other point about that is that the direct immunofluorescence on nonlesional, non sun exposed skin, it was previously called the Lip BuSpan test. And that was a test that people did if they were looking for multiple immunoreactants, compliment, IgG, IgM, hoping that if there were more of them, that it correlated more with renal disease. But again, that predated things like the double stranded DNA in our complement tests. And I don't think getting a lupus band test is considered very useful these days.

Okay. So I jumped into the slide a little too quickly. I wanted to begin by asking our panel of experts to declare upfront what they would like their takeaway message to be and advice to rheumatologists and APPs who care for lupus patients, what would be a good takeaway that you'd like to begin with that they might get from a session like this? Doctor. Nicholas, why don't you give us your suggestion for the audience?

I was hoping you'd forgotten about that part, Jack. So I would just really like rheumatologists to have some comfort level in the initial and basic assessment and management of cutaneous lupus. There's a lot that rheumatologists can do to really help their patients. And actually the third pie chart here, I'd love to get into a little bit because I love, I love, love, love that we get to talk about that.

Okay. Doctor. Fernandez.

Yeah, think going back to just evaluating a patient and determining if you think they have cutaneous lupus. I think an important objective is just to recognize that there are really only a limited number of subtypes of cutaneous lupus. They all have some features that do not take that long to learn. And if you take that time, I think it can really help you in evaluating patients to determine what on their skin may be cutaneous lupus and what isn't. And I should I should say that a reason I think this is such an important objective is that I do spend some time adjudicating for clinical trials for systemic lupus just the classy scores and I think what I see every day that I'm doing that is clinicians attributing any rash as being cutaneous lupus when most of what I see is not.

Yeah, you may have heard of Grainwald's Law of Lupus which is if a patient has lupus and anything that happens to them is immediately attributed to lupus, unless it's immediately otherwise obvious. And yeah, every day contact dermatitis, rosacea, fungal, like all just chalked up to lupus.

I like that. Doctor. Worth, do you have a takeaway for the audience that you'd like them to get from this session?

Absolutely. I think one of the things that's important is to understand the impact of cutaneous lupus on patients' quality of life. They're really miserable. They often can't go outside in the sun. They can't do their normal activities.

The result can be permanent scarring and dis pigmentation. And that has such you know, sometimes I have conversations with people and they really minimize the skin and think that it's a kidney and the brain that's so much more important. But if all you have is the skin, that becomes super important to these patients. And I think the second thing I would like to say is that we don't think that for most patients being on oral steroids is the long term approach that we should be taking. We have really a lot of other options for treatment.

Excellent. And Doctor. Richardson.

Well, now that my co panelists have determined you should know all about diagnosis, workup, and treatment, I don't know what's left for me to say, but I do hope you come away, each of you who are on here with some a few pearls, right? Something new because we're going to say a lot of things that you know already because you're astute clinicians, but hopefully you pick up something from us and our perspective as dermatologists. And maybe if we have time, we'll talk about or get to the fact that there are some new treatments on the horizon that we're pretty excited about and we really haven't had much for many many years or decades, but hopefully everyone can find something to take away.

Excellent, so let's get to that third pie chart there. There's a true false question and I'll ask Doctor. Nicholas to address it first. Again, 200 rheumatologists when asked through false photosensitivity can be discerned by history, eighty plus percent said that that is true.

I love I love that. I hope that this is helpful for people. So I have both just experiential and actual data that this is not true. So there have been studies that have shown, they ask people lupus patients, are you photosensitive? And they either say yes or no.

And then they test them all in a controlled environment with UVA, UVB, or visible light and they see, are they sensitive to it with their disease? And at least thirty percent of the patients that say that they have no photosensitivity do have measurable photosensitivity. But I've definitely found that clinically, when I really dig into it, when when you just ask them, does the sun make you worse? They may say no. But then you have this very photodistributed eruption and or when they really start thinking about it, you point out, you know, you may have a systemic flare even a day or two later, there's maybe a delayed effect.

They start to piece it together and so, I think that this is really under you know, sort of asked about and and addressed with patients. Particularly with patients that are skin of color that may not have had to really think about photo protection or had issues with the sun, you know, either, you know, in their family or personally in the past. So, this is a real opportunity to help with disease control for patients and not just cutaneous disease control always, but sometimes systemic disease control. So, really digging into this with your patients and saying, you know, most patients actually do experience this and obviously some antibodies more than others, but particularly if you're seeing clinically a distribution of disease that's very photo distributed, please address this with your patients and talk to them about photo protective clothing, seeking shade, sunscreens and tinted sunscreens are very, very important, especially for skin of color patients, but also if you're trying to address any pigmentary changes, the tinted sunscreens that have iron oxide are really, really, really important. So, love that we can drop that in, but I'd be happy to hear what my co panelists have found in their practice as well.

Yeah, think most of us think in rheumatology side that, yeah, it's that your rash comes out and gets worse off on exposure, but you're telling us that a photo distributed rash finding, even though they don't complain of worsening, is a sign of photosensitivity. Doctor. Richardson, any comments on that?

Yeah, I guess a couple of things. This may not be true, but I just go in with the assumption that every one of my patients is photosensitive, because I can't really tell from their history necessarily, and they can't either, and I don't ever tell a patient, Well, I don't think yours is photosensitive, so don't worry about sun protection. I'm counseling all of my patients about sun protection. So I'm in Upstate New York, I'm in Rochester, everyone's favorite place to go when it gets cold, which is most of the year, is Florida or The Caribbean, right? And so they go and they have the cruise for a week and they're fine, and then they come back to Rochester and their disease flares up.

And that's because there's often a delay of at least several days, if not a week or so, in their cutaneous symptoms with a good sun exposure, and they're not really putting it together. Things were great on the cruise, they're bad in Rochester, but really it was that big sun exposure while they were gone. So understanding that there's a delay in the flare I think is helpful to educate patients on as well.

Any other comments on photosensitivity, any of the pearls?

Yeah, I mean, I'll

go ahead. I

was just gonna say that sometimes I do think the systemic flare is also worth considering and patients can have arthritis, they can develop new onset proteinuria in the setting of getting too much sun. And so you really can't emphasize enough about the importance of sun protection.

Yeah, I agree 100%. But the one thing I will say is when I counsel patients about protecting themselves from the sun, I do make a point to try to tell them that we're going to try to find this balance. Don't think we want to

send the message in a

way where people think that they have to stay inside and live like a vampire only come out at night. I mean the idea is still to optimize their quality of life but to allow them to get enough exposure of the sun that they feel like they're living a good quality of life but not so much that it is aggravating their lupus regardless of what organ systems are involved. And I feel that that approach gets more buy in from patients and they're more likely to actually listen to how I tell them to sort of address avoiding the sun at certain times.

One of our questions goes to our next survey question, which is the dermatopathology that you see, especially if patients are SFA positive, that it could be lupus, it could be dermatomyositis, especially if it's the cat on clinically a myopathic DM. What's your comment on again, the importance of pathology in making a CLE diagnosis and where are the pitfalls? Who wants to run with that bird? I can take a stab at that. Think, look, I think

most inflammatory rashes in dermatology to make a a truly accurate diagnosis require that clinical pathologic correlation. So, I definitely think pathology is important. And I do think in the appropriate clinical setting, if you have the appropriate histopathologic findings, you can be close to 100 with your diagnosis. I think the biggest pitfall is what Vicki pointed out is that the overall histologic pattern, the interface dermatitis with increased dermal mucin just from a histopathologic standpoint you cannot tell the difference between lupus and dermatomyositis in most instances. And I think sometimes you get some weird drug rashes so the other entities that can present with interface dermatitis can be a little bit challenging but if you're clinically astute and you know lupus on the skin and the morphology, I think you can usually tease out the pitfalls and be pretty accurate.

I'll just add a couple things. So hands and feet when you biopsy them are very tricky with a lot of different diseases. And so, interface and a lichenoid pattern can sometimes be similar. I've had a couple dermatomyositis patients whose biopsies initially were read as being lichenoid. So that's a potential pitfall.

It really depends on the dermatopathologists. And sometimes nowadays slides are being sent to regular pathologists and I found a tremendous amount of variability in how well those are read. So just emphasizing what Tony is saying, like you really, the times I've seen people go really, really wrong is when they put all their eggs in the pathology basket. And you really have to put it together with the full clinical picture. The other thing that can happen is if you have a really super exuberant interface reaction, someone had mentioned Rowell syndrome, you can have this erythema multiforme Steven Johnson sort of appearance with necrosis and necrotic keratinocytes.

And so that can throw you off as well. So just know that it's one piece of data, that's super, super helpful piece of data, but it's just like an ANA. I always joke with the residents, it's like an ANA of one to 160. Like maybe it's a thing, but maybe it's not. We need to make sure that it fits with everything else we're seeing.

Yeah, I want to just piggyback on what Matilda said about not putting all your eggs in the pathology basket. So I'll tell you maybe five years ago or so our group pathology group at the Cleveland Clinic started requiring that every in house biopsy pictures are taken of the patient and the location and I cannot tell you how much that it's proved our accuracy in making a diagnosis because sometimes, you know, either clinically or histopath ology, not all the clues are there but when you have both, you can usually arrive at the accurate diagnosis.

So, again, Matilda brought up this issue of it'd be great if it's read by an experienced dermatopathologist that does a lot of lupus skin and whatnot, but often it's not. It's often it's the community. I mean, all of you work in centers where you have the experience. I work, you know, very closely with Clay Cockerill, who does a big thing. There's a new nationwide thing doing a lot of dermatopath, which is kind of neat.

So how do we, what should the rheumatologists in practice in the community, how can they ensure they're gonna get the right reading, and is there a role for AI in reading dermatopathology?

I would say something quick that I don't know, I don't have an answer to the AI, but anybody who gets the biopsy should feel free to question the pathologist or the dermatopathologist. If it does not look like it fits with what you're seeing, it's time to send a note, pick up the phone, and talk through things, because as Tony's pointed out, really that clinical pathologic correlation is key, and sometimes if we're not familiar with the dermatopathologist, you know, they're not our buddy in our system, we're hesitant to do that, but I think that's a really important part of arriving at an accurate diagnosis.

I would say very often I will actually, if I see a patient where the histology is not fitting very well, we will request the outside slide and do a second read. It may require getting approval from the insurance company but it can be really important in terms of making sure that you know what you're treating.

But I think initially, Jack, whoever, whatever pathologist is reading the biopsy, if a clinician, rheumatology or otherwise, really is wondering if that's an accurate read, As Chris pointed out, calling that pathologist, sending the pathologist pictures, you know, I get pictures from outside clinicians through email nowadays, and private practices have these even the pathologist, and even having the conversation or including it in the email some clinical information that is thought to be important, whether they're serologic results, you know, about ANA or other anti ENA antibodies. All of that can help a pathologist go back to a slide and see it through different eyes.

Okay. We have a question from Jorge Rojas on something of Rowell syndrome or a targonoid rash with SLE or other, what in the world is a targetoid rash or Rowell syndrome?

It depends on who you ask. Some people feel very, if you wanna have a dermatologist have a fist fight, you can bring this up. Some people think that it is an erythema multiforme like presentation that's occurring in a patient with lupus and other people think it's just a super, super exuberant interface dermatitis. I probably fall into the latter just because I'm a big fan of Russell and that's what he thinks. But, and just based on what I've seen, but that's really what it is.

Are these like erythema multiforme targeted sort of edematous plaques that on biopsy have more necrosis and they look more indistinguishable for like a Stevens Johnson's or other things, but you have to be very careful that you're ruling out other causes of an erythema multiforme like rash in that patient before you can sort of comfortably land on that presentation.

And to make it more confusing, I have a patient who had this diagnosis of Rowell syndrome, and it turned out after I started seeing her, she got a flare of it every time she got fluconazole, and if she didn't get fluconazole she didn't get it. So it was actually a fixed drug reaction that she was getting on her palms, and she also has systemic lupus.

Also indistinguishable on pathology.

Yes, so you just have to take the whole situation in perspective. And who made the diagnosis? She made the diagnosis, because eventually she came to and said, Hey, I got fluconazole again and I got this rash. I knew what the name of it was, but she was pretty astute. So you do have to listen to your patients too about when these things happen.

So when rheumatologists were asked, can you distinguish a drug induced lupus rash from a non drug induced lupus, they're split down the middle. And I think it's for a lot of reasons that were already stated here, but I'll ask each of you to address this question with a pearl as to how you can distinguish it, or you should, maybe I should worry more about drug induced lupus with the following drugs. Why don't we begin with Doctor. Wirth?

So I think that traditionally, it's subacute cutaneous lupus is really the subset of cutaneous lupus that we worry as being drug induced. And it's very different than a drug induced SLE, which is a different set of drugs and actually where the skin rash is not really even cutaneous lupus, it looks somewhat different histologically and clinically. But with subacute cutaneous lupus, you really can't that much differentiate that from just idiopathic subacute cutaneous lupus, although the distribution of the rash may be a little bit more. It might be more on the face, more on the extremities, but you can see an SSA, SSB antibody associated with that. And what I will say is it's so important in such patients to take a careful history about their medications so that any patient who tends to get subcutaneous lupus, they're often older and they're often on meds.

And it's very often that you can really track down that there's a med rep involved. Now I will say that there are over the counter meds such as PPIs, omeprazole, that are probably the most common cause of drug induced subacute cutaneous lupus, and that's not gonna be on the drug list that the patient's getting to get over the counter. So you really have to take a very, very careful drug history on these kinds of patients.

Okay, I agree. Any other comments on DLE, I'm sorry, drug induced lupus and differentiation?

Just one, I mean, Vicki, I think went over everything that I find important. I would just say most, and there's a little data in the literature about this, but most of the time SCLE is waist up. And if it's on the legs, some might call that widespread, I think that's a clue for me to really, really dig into the medication history thoroughly. A regular run of the mill SCLE I don't see on the legs very much, but drug induced can be. So, Becky talked about distribution, think that's the cutoff point where I think, oh, I really need to dig further.

But enough SCLE is drug induced that really you need a thorough drug history for everybody.

Yeah, I've seen it quite a lot unfortunately. The other clue is that in drug induced male female equal predominance, unlike in classic SCLE, and there's some data too that the actual eruption's more severe, so you're starting to see like sloughing, a lot more edema, they're just angrier looking frequently or disease that's just really recalcitrant. And I think it's especially tricky because see a ton of PPI induced SCLE and patients may take those medicines intermittently and they might not even know what they're called. So I'm just like, do you take anything for heartburn over the counter? Terbinafine, I see a lot, a lot of also, but unfortunately it's pretty common.

I see a lot of referrals that are on systemic meds for SCLE that actually there's this drug induced.

Okay.

The other thing I would say is that patients who have SLE and don't have SCLE, I think they're at increased risk when you give them some of these drugs to have a reaction. And because they have a background of SLE and then they get their PPI or their terbinafine and they blossom forth with SCLE. And so there's probably some kind of genetic risk factor involved.

But then I would, is that analogous to the situation of patients with lupus shouldn't get drugs that cause drug induced lupus because the lupus may get worse. I don't think that that's true. But does anybody have a different view? Yeah. Think we just need

to be aware it could and watch closely for a new rash.

Okay, so we're gonna get next into assessing patients with CLE. So TruePulse pathology can diagnose lupus with 100% accuracy. Two thirds said, no, that's not true. And I think we've heard that that's not true, but that the pathology needs to be carefully reviewed and jive with the clinical situation. The interesting thing for the four of you and the audience is overwhelming message from you and also from our renal lupus people is, know, you really should get a biopsy, you know, because, and I would say that I'm one of the guys who's been at the medical school and then also out in practice.

Out in practice, we often don't get biopsies because they probably don't need it. That's our excuse. But the bottom line on that is I'm left to guess about what's going on either in the skin or the kidneys based on the scenario or what I see. Whereas my colleagues who are teaching me are saying, get the renal biopsy, repeat the renal biopsy, get the skin biopsy, because you're more likely to know with some greater assurance. So I think this is still a strong message that we're putting out this month that biopsies are really needed.

So the next question was, in your patients who have cutaneous lupus, and let's just say CLE alone, non systemic disease, how would you assess disease activity? And seventy percent said history and exam, twenty one percent a derm referral, and no one is really relying on official measures like SLEED eye or patient reported outcomes or survey form. Do you think that that's a good idea, Doctor. Nicholas?

I think you're muted, Maddie.

Yeah, sorry, my kids were like opening and closing the garage door. I think it can be challenging for people that aren't used to assessing cutaneous lupus to know active from inactive disease, particularly with discoid lupus, where there's a lot of sort of chronic damage that may not indicate activity. And I think Vicki's published a lot of really fantastic stuff on that and the value of the sleet eye when it comes to to that sort of thing. But at least having the concept that, assessing because some scarred areas from discoid can still be symptomatic. So history and exam may not be enough.

Also, if you're not very experienced with skin of color, it can be very difficult to see subtle signs of activity like erythema. And so I think that it's nice to have a little bit of training and be a little bit more exact. Sometimes patients are very good at telling you if their disease is active or not, and sometimes they're not so much. So I think using a little bit more of a structured tool can be really helpful. And my only pro that I would add is if you're not used to looking at skin of color and you're trying to learn how to see erythema and skin of color, it's easiest to just ask the patient.

Does your skin look red? Show me where it looks red. And the more you look at it and the more you let them teach you, the better at it you get.

Yeah, so I made up a slide here on the left about how we might assess clinically cutaneous lupus in practice. And one would be to get the diagnosis right. And then there are other factors that our faculty like to address their advice for people in the clinics wanting to do a better job of assessing them in addition to what Doctor. Nicholas said.

I would add that a picture is worth a thousand words, and if you can take pictures and put it in the chart, you're going to be able to see if things are better or worse, a lot better than trying to remember or relying on the patient to remember. And so I am always trying to get pictures in every visit. And then the things that I tell my patients on what to treat, right, because they'll just keep treating a spot over and over and over when all they have is maybe post inflammatory hyperpigmentation or something. Is it red? Is it rough or scaly?

Is it tender or itchy? I think that covers most of it, and so if you're looking at an individual lesion, if it's still red or flaky or, you know, it's tender when you touch it, that's a spot that probably needs to be treated. And then overall I'm always asking my patients, Do you have any new spots? And then I'm comparing to pictures. And if it's expanding, well it's active, right?

So those are just some basic things that probably pertain to most skin diseases that you could take home with you, but particularly for, I think, cutaneous lupus, which can be flaring in some areas and inactive in other areas, and that can always be changing.

I'm going back Jack to just what I first said. Think I personally think you know there are many different practice settings and of course and you know just very busy practices I do think history and physical exam is adequate to assess cutaneous lupus patients from visit to visit. However I think the key is you have to feel confident that when you are examining the skin, you know what is cutaneous lupus and what isn't. And you show the classy tool here. And this is what I see when I'm adjudicating.

This is what clinicians around the world are filling out. Presumably a lot of them rheumatologists because they're for SLE trials. And I just see everything that doesn't have the color of normal skin being graded as active cutaneous lupus. So I think no matter how you want to evaluate I think there are many different ways to do that that are fine but you have to be knowledgeable and confident about what is cutaneous lupus, what isn't, what is activity and what is damage. And then you can really be an important tool to help your patients get the good outcomes you want them to have.

Doctor. Hurt, well, Vicki, I want get to the classy.

Okay, go ahead.

You could add on that. So, Doctor. Fredrick brought it up. CLAS C is a tool that's being used in clinical trials, but can be used in practice. Since it has its origins with you, Doctor.

Wirth, can you talk about the CLAS C and how it's being used?

Sure. So we initially, as you can see, there, Jorg Albrecht, who was a fellow with me decades ago, worked with me and developed the CLASI along with other people and patients to measure skin activity and damage. And what we try to do is to look at, we've talked about extent of the disease, this is a way of telling where there's erythema, where there's scale and the degree of them, both of those items in different parts of the body. And so this is a way of really more granularly being able to measure disease activity. The bottom part there is all about hair loss, which is a whole discussion we could have.

The middle is about lesions in the mouth. And on the right hand side is damage. And one of the points I wanted to make about damages, if you ask the patient, are they better? Sometimes they're gonna tell you no, even when they are because they don't realize that damage means that basically the activity to a certain extent may have gone away and they're left with damage. And so I do think sometimes in darker skinned people you have to almost explain to them what the expectation might be of what's important.

And so with the CLASI we've tried to differentiate between activity and damage and for the investigator or the clinician to really think about that as they see each part of the body. So this is a way of coming up with an activity score on the left bottom there and a damage score on the right. And now in clinical trials, we're able to use this to look at skin activity both as a primary outcome and a secondary outcome in SLE trials but a primary outcome in CLE trials. And this is a huge advance and there's been a group that's worked very closely with the FDA over a number of years and just very recently the CLASI is now being able to be used as a primary outcome. And that is really opening up the door to a lot of very important trials that are gonna make treatments better for our patients.

I think it's brilliant because lupus trials are hard enough to do. And to do them on the basis of a SLEET I2K or an SRI4, with a general lupus indication, I think it's inferior and it shows up with really high placebo responses around fifty percent compared to a specific organ endpoint like renal lupus and lupus nephritis. Now, if we can add cutaneous lupus that has a primary endpoint like the class A, think there's a major advance in getting drugs studied and approved. Any other comments on this? Since many of you do clinical trials?

Doctor. Fernandez?

Well, I think we agree. And that working group that really communicated over time with the FDA to sort of work out what the issues were on that side I think was very successful. And of course Vicki played a huge role in doing that. But I mean one thing I'll say is I do the Class C tool on every patient that I see in clinic. It doesn't take that long.

And so I do think that if you no matter how busy you can do it and it can be valuable to you to really know where your patient is and where they've come from and track or need to make a change in treatment.

Only thing I'll piggyback on what Chris had said, I think particularly when it comes to hair loss, when we have slow improvement, is the only kind of improvement that we get with hair loss, patients do not remember well, right? So they'll say it's no better. And then you pull up a photo and they have like 50% regrowth. And I just can't tell you like the surprise and delight you see on patients faces. So totally, totally agree with Chris's experience and recommendation there.

Yeah, pictures are invaluable. Our next, second to last question, we should get through this quickly. Co management, again, the two thirds believe derms are mimicking. I think the right answer there is while many of them present with skin findings to primary care rheumatologists, maybe the diagnosis does rest with the dermatologist. And then who manages cutaneous LE in your practice from the 200?

Oops, sorry about that. From the 200 that were surveyed, you can see that most felt that at least half are being co managed with a quarter being managed by derma and a quarter being managed by Rheum. What is your preference, Doctor. Richards?

Well, it depends, right? So if they only have cutaneous disease, I'm usually not sending that to my rheumatology colleague and I'm managing it myself. If they have some systemic disease, then I'm involving those who need to be involved, and it's usually starting with the rheumatologist, but it might be a nephrologist or whoever else. And so, I think anyone I see is either managed by me or co managed. I never really let them go unless they come to me for something that's not really cutaneous lupus.

I happen to find they have systemic lupus and they don't need to see me anymore. But most of the time I would say if they have other signs of systemic disease, it's co management. But of course I've got a great team to work with, and like you've pointed out, not everyone has that, so I'm pretty fortunate that way.

I think my practice is very much like Chris's where you know if somebody sends me cutaneous lupus and they because they're not interested in playing any role in managing it or if I'm diagnosing it then I just manage it but I am always happy to co manage with rheumatology. Even you know sometimes they some of our rheumatologists like treating cutaneous lupus and if they have a patient that who only has cutaneous lupus and involve me, I mean I'm certainly not going to say, hey you know I should be treating this patient. We co manage and I think that's one of the nice things about being at a big center is you have a lot of colleagues to work with and learn from and to help patients get better.

I would imagine there are a lot of dermatologists that as soon as they see lupus, they want to wash their hands of that though. So you're probably getting referrals as rheumatologists from dermatologists in the community usually that just don't want to be managing immunosuppressive medications or other things, and then you're just kind of stuck managing them. You may need to reach out to an academic center that is close, meaning within five or six hours depending on where you are, to get an opinion. But yeah, we're a little bit of an odd group here, right? We're a focused group of rheumatologic dermatologists, so just keep in mind not every dermatologist is going to be jumping at the chance to independently or co manage lupus.

Having said that, we do have a Rheumatologic Dermatology Society and that group is really very focused on diseases like lupus and really expert. And I would say most big academic centers have somebody who makes that their priority in many ways. And you're gonna find a lot of variation in how the collaborations are done depending on the skill set and the interests of the practitioner.

Excellent. Okay, our last questions were on treatment. This is kind of a simple question. What's hardest to manage? The winner was lupus profundus followed by discoid followed by lupus tumidis.

Most people felt photosensitivity was not hard to manage. Anyone wanna comment on this almost silly question, but does it ring a bell with any of you?

Well, it's interesting because lupus profundus is quite rare, but I think all of us are very, some have trepidation when we start seeing these patients because they can be a bit more refractory. I think the approach to treatments are not that dissimilar from what we do with other subtypes. But I think it's because it's deeper, it's harder to evaluate and potentially can be also in its own way, you know, you get atrophy in the skin that could be very concerning.

So in the world of lupus, it's a major no no for anyone to have lupus and not be on hydroxychloroquine. Does that mean that maybe you guys are being put out of business that we're averting all the lupus skin disease by ubiquitous use of hydroxychloroquine? Anyone think that might be true?

Would that be amazing? I mean, we have referral bias because if a patient's cutaneous lupus gets better and hydroxychloroquine, we don't see them, right? So, all of my flaring cutaneous lupus patients are on hydroxychloroquine, almost all of them. So, sadly, sadly that has not been my experience.

That goes to the next question. Go ahead, Chris.

Oh yeah, you know, when you can't use hydroxychloroquine, what's the best option? Really depends on why they're not using hydroxychloroquine. So for those patients who do get a drug rash on hydroxychloroquine, almost invariably I can put them on chloroquine, and they're fine. They don't get a reaction to the chloroquine, and I think that's maybe an underutilized pearl because I really think antimalarials really is the first line treatment for first line systemic treatment for cutaneous disease, and Vicki's gonna pipe in and say, Don't forget quinacrine, and when it was more available, I loved it. I would just give one hundred milligrams of quinacrine once a day to the patients on hydroxychloroquine, I call it a plaquenil booster for my patients, and it was fantastic.

I'm looking forward to the day when it's more readily available, you can get it in a few places. Cutaneous disease in that way is no different, you're going to start with hydroxychloroquine for almost everyone who needs systemic disease treatment, but I mean the four of us have tons of patients on methotrexate and mycophenolate and other things. As Maddie said, if they cleared on hydroxychloroquine, we probably aren't seeing them in the first place.

I will add that it's really important, and I think rheumatologists know this, just like with systemic disease, there's a significant lag, and skin disease can take four to six months of treatment. And so, if the patients don't understand that, they may stop taking it early. So, I think that's, it's extra important to counsel them on that. And especially in discoid that you know even if they have some old lesions in the redness as Doctor. Richardson was saying, the redness scale everything's gone away but they're still dark and that doesn't mean that the black one is not working.

Also you know it's obviously

it's safety profile is so much better than the other systemic agents we use. So for me, even when I feel that somebody is not doing well on hydroxychloroquine and I'm really thinking about adding another more immunosuppressive agent, I do try to talk to a patient and try to gauge whether or not they're really compliant with taking hydroxychloroquine. And I think that's a little bit tricky like I never want to be accusatory but I want to try to tease out are you missing certain days of the week. So for me I really try to make sure that patients give it an adequate trial before thinking about adding a more immunosuppressive medicine. As I'm sure everyone on the call knows there's a lot of literature about checking whole blood levels.

I don't do that probably as much as I should but I do at least try to get a sense if a patient is taking the medicine the way I prescribed it on a regular basis before adding something more immunosuppressive.

So in the last two minutes that we have, three minutes that we have, I'd like you to address where you see the newer drugs, the anaprolimab, belimumab and voclosporin and how you're using those in your patients with CLE. Why don't we begin with Doctor. Wer.

Okay, so voclosporin is approved for nephritis and there's no literature in terms of cutaneous lupus. So I'm not using it. It's very simple. Balimumab, there've been a number of studies. It definitely can work for some patients.

It takes a long time to work. It can take five months. And most of the studies suggest that the efficacy, it takes a while and it may not be quite as effective as some of the newer agents coming along. Anifrolumab, there's been really a flurry of literature. We know from the SLE trials that it worked in the skin patients who had SLE.

There's been case series and there's now an ongoing trial for CLE. And so I think we all know that it's a lot of patients can respond quite quickly to the drug and do quite well over time.

Yeah, I

would. I've had really good experience with anifrolumab, not universally, but in a lot of patients, especially discoid and psoriasiform SCLE seems to respond really well. And especially even in patients that have failed most other things. And then, some of the early trials with some of the other like plasmacytrate dendritic cell inhibitors and things are looking really promising. And then I think we sometimes will throw in JAK inhibitors topically, you can have this compounded.

So a lot of exciting things coming down the

pike. Chris?

Yeah, for me, the question is belimumab versus anifrolumab, it's not a question.

Like

belimumab rarely works, it's super slow if it does. I haven't had a patient fail anifrolumab because of lack of efficacy. I will, I will, but it is game changing and lightning fast compared to basically everything else, and I've had patients who couldn't work, who were disabled, who now are back to work, and it really has changed their life. So I'm always pushing anaprolimab over belimumab when that question comes to me.

It's interesting that you say this in light of the sub analysis of anaprolimab showing that those who had the high type one interferon signature had the best skin and joint responses. Whereas if you try to look at lupus responses based on type one signature, it wasn't so dramatic. But for skin and lupus, it was significant. Doctor. Fernandez?

Yeah, so I'll just quickly Jack say that it is very exciting that some of these medications including anifrolumab, litifilumab, dacravacitinib, their clinical trials that are really the primary endpoint is does this medication help improve cutaneous lupus? So, know, it's at some point there may be FDA approval for some of these medications that we're talking about specifically for cutaneous lupus patients regardless of whether or not they have underlying SLE. So, I know we're we're in dermatology very excited about that.

All right, so we got a bevy of questions at the very end. I don't think I can get to them. Let me see if there's a, how do you deal with cresiosis from antimalarials? Basically, it doesn't go away. You stop the drug or or you tolerate the the slate gray appearance.

It's rare, but does anybody have a way of dealing with that?

Yeah. It's short of stopping the drug and and time. It takes a lot of time for it to get better.

It will fade.

Yeah. A question about whole blood levels of hydroxychloroquine. What we learned from Michelle Petrie recently, and talks a lot about this, is that it's like an A1C for compliance. You don't need to check it at any one time and whatnot and there are different methods of checking it but they're all sort of valid. You need to target.

I think that target ranges like 900 to 1,500. I don't know if any of you have a different opinion about that. And let me see if I have another last question. Anybody able to comment on that? Okay.

Let's end up at the top of the hour like we're supposed to. I wanna thank our truly expert panel, Doctor. Victoria Worth, Matilda Nicholas, Anthony Fernandez, and Christopher Richards for a really great session that's gonna be recorded and gonna be seen by a lot of people. Tell your friends, it'll be in podcast form as well. Tune in next week where we're gonna have another Tuesday night rheumatology and we'll be discussing anti phospholipid syndrome.

That should be I think a knockdown drag out. Everyone's got something to say about anti phospholipids. Folks, thank you very much. Have a great night.

Bye.