 Thanks for being here and thanks AHS for allowing me to be here to teach everybody a little bit about lupus and where it may have come from So as Tommy hints it out. I'm a naturopathic physician dwelling in rheumatology I'm in an integrative practice setting with a rheumatologist And so we we have a lot of fun budding heads and arguing talking trash back and forth Breast implants really interesting discussion. We had recently in other etiologic factors in autoimmunity You know me coming at his prednis zones and poisons and him at my stuff that supposedly doesn't work But we get along and we're a good team and he's seen that in his observation over the years working with a lot of different Nets paths that when Our patients implement the things that are taught here at the ancestral health symposium and These lifestyle sorts of things these patients can really reduce their need for medication, but so why rheumatology? Really interesting stuff, you know It's just fascinating autoimmunity and the number of ways it can present and this this kind of very good Be really schizophrenic and it's just a lot of fun to try to sort out But it's it's never lupus right nunca lupus. I was just talking to Luisa here. So anybody watch house It was lupus maybe one time so a little bit of Just on the sort of presentation of lupus before we get into it It can present in a lot of different ways and there's really two depictions here So the the wolf in the butterfly which we're familiar with that butterfly logo a lot in these different lupus organization groups and then the wolf so the disease can be really violent and Unpredictable and so I'd like to share two cases of women that I've worked with just to give you a Kind of idea on how it can present so s post menopausal women in and out of hospital since she was very young lupus-like features coming and going Never really present all at the same time and coherently in a way that would allow anybody to put the picture together Very easily and so she'd gone from clinician to clinician being labeled with anything from depression type 1 diabetes Glucosis regulation was part of the way hers presented widespread lymph adenopathy. So maybe it's lymphoma or cancer. Maybe it's anti-phospholipid syndrome. Oh wait a sec Some other strange complication here and then they're back to cancer And then back to depression and then you know, she doesn't get any support from her family members It's just really tough and so she's had a lot of the treatments out there steroids Imuran prednisone benlysta Cyclosporine she's done it all her saving grace primarily was plaque when all which she recently stopped tolerating because of a Hypersensitivity response to a recent neck procedure So some time ago her husband phoned me when I was doing house calls and said get over here now and I go well What's going on? My wife my wife's not well And so I get there and she's she's on the floor in the hallway and her husband's next to her and In my mind. I'm like why haven't why didn't you call an ambulance? What the hell's going on here? And she's breathing she's tachycardic her blood pressure is a little low So she's drifting and out of not being stable, but she's talking to me And so I'm like hey, I'm gonna call 911 and she's like well. No, you're not and I'm not going do something and so Fine I'm a natural path maybe a bad call in my book But I put some acupuncture needles in her and gave her a potion and she perked up in a few minutes And despite dramatic improvement with prednisone, which she was instructed to take For autoimmune involvement of what turned out to be her pancreas. She ended up calling that quits and didn't feel like she needed it So that's her and then you've got other women who you know, maybe just have a little bit of joint pain Just have a little bit of nausea some rashes This recent case I saw young gal well most of her life and will likely be well and so No major organ threatening disease come back again and see me in six months And so we've got this wolf depiction and we've got the butterfly My cursor disappeared here So here's our objectives So just a brief overview of lupus to teach everyone here what what that is and what it might look like and then is there a Explanation for the genes that predispose for lupus So a brief history for the longest time lupus was thought to be a disease with only cutaneous or skin manifestations goes as early back as Hippocrates between 460 and 350 BC to describe these cutaneous ulcers under the heading of herpes S The Amenos this is Rogerius here in the 13th century who described the skin manifestations Manifestations on the face is similar to a wolf bite. And so that's why you see that wolf depiction that I listed earlier the Skin lupus has a lot of different flavors Sorry, I'm having a little difficult to hear Tommy. Could I get your assistance real quick? I just need the the cursor to pop up so I can drag this down Okay So we could see it on the screen There it is. Yeah, thank you Yeah, I just want this I just want this to be able to slide down Yeah, but then so then you're not using that okay click forward and then sorry guys Okay, so skin lupus has a lot of different flavors the two most known are discoyed lupus attributed to the French dermatologist Caysnave in 1833 and then the malar rash or the butterfly rash that goes over the cheeks and over the bridge of the nose is described by the austrian physician von hebra in the Neoclassical period it became more widely known as a systemic disease and this is Moritz Kaposi here One of the first describing that it could involve all these other organ systems And then of course William Osler if there's any physicians in the room You may have heard of him further confirming the systemic nature of the disease in 1895 And then the biggest event in the modern era was this the discovery of the lupus erythematosis cell by Malcolm Hargraves and his colleagues at the Mayo Clinic in 1948 so this is around the time that prednisone was discovered as well and there was a lot of developments leading to the better care for these types of patients and The discovery of the ANA test Which Helped diagnose lupus more sensitively and so as I mentioned before we've got the butterfly in the rat the wolf here the butterfly Kind of describing what I like to call this soft this more soft Presentation of lupus not so severe more limited forms that maybe just involve the skin and the joints Characterized by that maylar rash maybe a little achiness get better with some NSA and said some plaque when ill See again in a few months, and then you've got the wolf representing what we refer to is hard lupus violent Unpredictable relenting unrelenting organ threatening involving the brain kidneys heart lung pancreas women in and out of hospitals steroids benlysta rituxin cytoxin very violent and unpredictable and So lupus is an autoimmune disease with protean manifestations, which means the clinical presentation can be incredibly variable It's a really fascinating disease and ultimately the springboard for our understanding of many different autoimmune conditions out there As I mentioned before it can affect any any bodily system one two fewer several some all at the same time Some here others there Maybe Sue was spilling some protein in our teens had some fatigue and joint pain in her 20s Some pancreatitis in her 30s and then having everything together in her 40s And then there are certain serologies we look for which are really a headache Especially for patients out there who maybe don't get very clear explanations from their clinicians who order them And they have names like a NA Double-stranded DNA Smith row anti histones sometimes they're there with the clinical features other times they're not My primary care provider orders an A&A and it's positive So I have lupus and to that I say not so fast lupus can mimic a lot of different diseases out there and it's often been called the great masquerader We get some nice sound effects here And this is why it's so frustrating for the patient again So one of my favorite type of consults is the patient comes in with an A&A that somebody ordered And then we have to try and sort it out And so it takes a lot of detective work and I don't always have the answer because Sometimes it's the A&A and they're just not feeling well and very little in terms of more specific signs and symptoms And it can explain this explains why it takes years or decades for some of these women to be diagnosed In terms of the epidemiology conservative estimates by the CDC estimate the prevalence to be around four 500,000 individuals in the US With the most liberal stats stating that 1.5 million in the US are affected with up to five million worldwide and the disparity in those statistics primarily has to do with how difficult it is to diagnose the disease and the heterogeneous nature of the presentation and This is a disease that tends to go after women as do most autoimmune diseases So nine to one ratio as high as 15 to one in some studies women to men and One of the main reasons for this is thought to be estrogen. So women make more estrogen and There were some case reports interestingly when birth control pills first hit the market in the 60s where women were essentially reporting lupus-like syndromes or flaring of their diseases and it's it's fascinating how things have changed in terms of birth control and the amounts of estrogen that are orders of magnitude lower today 150 micrograms in the older stuff in 25 to 50 in today's There tends to be higher prevalence of the disease and severity in the mind in minority groups, particularly economic disparity and genetics Explaining that and we're going to focus a little bit more on African Americans today How it's diagnosed So we take a history. We do a physical exam. We run some labs the old criteria Looked for a minimum number of characteristic signs and symptoms requiring four out of 11 criteria. There's a Acronym that we had to learn in med school and I'm looking at dr. Rob Abbott now because he was probably tortured by that as well So characteristics skin lesions painless oral ulcers symmetric Small joint involvement photosensitivity or flaring of rashes or disease overall in the sun low blood counts kidney involvement Low white counts and then specific antibodies, of course in a and a This is the new classification criteria out of the European League of against rheumatology and the ACR endorses this as well. And so essentially what you need here is 10 points from this blue area here and a few points from this green area Which makes things difficult. So you have to have Antibodies and you have to have symptomatic criteria here And so there's more to the story in the serological department than a and a we've also got double-stranded DNA and Smith antibodies Double-stranded DNA tends to be more specific for Caucasians and Smith for African Americans And then there's other antibodies like antiphospholipid syndrome And I think they should mention Hashimoto's antibodies in there as well because that's a common overlap feature of Autoimmunity and lupus and when I say Overlap syndrome, that's the ICD-10 code that we use to describe these sort of poly autoimmune entities How is lupus treated? So there's a wide range of pharmacologic interventions not listed here So a number of them I mentioned in S's case But the four main guys are plaque 1L, aspirin, prednisone and bulimumab. So only four FDA approved treatments Because of these treatments lupus isn't a death sentence as it once used to be All we had in our arsenal really in the past was just a ton of aspirin and so we've we've really come a long way plaque 1L is what we've referred to as a disease modifying anti-rheumatic agent or a DMARD Which essentially helps pull the reins back on the inflammatory response influencing these things we call toll-like receptors and Then if you're Into sort of the microbiome area it seems to have some Antiparasitic and antimicrobial action as there's there as well. So there could be some reason for disease Modulation there and then the other really interesting thing about plaque 1L is that it's an anti-malarial and kind of what I hinted at talking about here is malaria Plasmodium infection and we'll get into The story as to why lupus predisposition Exists and may have to do with that but unfortunately plaque 1L's mechanism of action doesn't seem to overlap in any way with what we'll be Discussing when it comes to plasmodium, but I thought it was kind of ironic how there was this Plasmodium sort of origin Component and how there was an anti-malarial Used as the mainstay for treatment. So kind of a funny coincidence So why does lupus happen and auto-immunity in general some of you may have heard this story before you have a set of life Instructions acquired from mom and dad most like everyone else's with your own little nuances And then we have these stochastic events a lot of which you've heard of infections toxic and toxicants in the environment Mercury silica and hydrolyzine have been studied in lupus Valates pesticides Nutritional factors like gluten casing lectins and so on These insults are thought to contribute to this sort of Preclinical stage where you have this immune dysregulation and auto antibody formation Which is another fun place for discussion because there's a lot of debate as to The presence of antibodies and whether or not that will predict the Development of an autoimmune disease later and there's research indicating that subset of people who do have Antibodies including high-titer antibodies at some point may never develop the disease And then finally we have the manifestation of the disease lupus or whatever you have the predisposition for And so the question we're going to try to answer here is why do we have these genes in the first place? okay, and So we already know about we have an idea of what some of those stochastic events are we're not going to focus so much on those But again, what is proceeding? these genes and So we're going to talk about mosquitoes and lupus in West Africa and this is a mosquito here Hopefully not trying to feed off of the floor, but not my favorite type of insect and this conjures up memories of some struggles in I'm a really anxious and sensitive constitution and part of that the way that manifests is as a light sleeper and so I recall these times Being attacked by mosquitoes trying to sleep and you know the thing goes by your ear a couple times And you know I was always a type to get out of bed and hunt the thing before I tried going back to bed And so you know I have these images conjured up of Running around the bedroom with my lamppost shined at the wall trying to find this guy so I could obliterate him After he's bit me five or six times so Exactly where do mosquitoes fit into the discussion as you know mosquitoes have played a very important role in the development of certain Genotypes more specifically sickle cell and certain hemoglobin opethies and this may also be the case for systemic lupus erythematosis and So the story goes like this In 1968 Brian Greenwood a British physician and researcher was working in Nigeria at the time He had noticed that SLE admissions to the hospital were four to six times less frequent than figures He observed back home in Europe and two other investigators confirmed his findings ten and twenty years later And notice that lupus seemed to be less prevalent outside in the community Even less organ-threatening manifestations Although you know our best evidence today reviews of lupus incidents and prevalence pitted against stats for lupus and endemic areas Aren't entirely supportive of this, but they're they're not quite complete either and so What this ultimately led to was This hypothesis where Greenwood proposed that paracidic infections particularly Plasmodium The critter that mosquitoes carry were protective against the development of certain autoimmune diseases He and his colleagues went on to do rodent studies showing that infection with malaria could delay SLE in mice geared spontaneously to develop lupus and other lupus like syndromes and Other investigators found that malaria infection in these lupus prone mice could induce remission of the disease The specific models being studied lupoid hepatitis and lupus nephritis And then also really interesting the anti-plasmodium antibodies extracted from the lupus prone mice could actually be put into the mice and Conferred a protective effect although that was much smaller than actually infecting the mice with malaria So all very interesting and recall that the prevalence and intensity of the disease seems to be more pronounced in African Americans this the the reason for that might have something to do with something called tumor necrosis factor alpha okay, and so the Tumor necrosis factor alpha is essentially a pro-inflammatory cytokine, which I'll just refer to as TNF moving forward It's a prime part of what we call your acute phase response so you have some kind of insult a bacteria a toxin a food protein and Essentially a fire alarm gets pulled and part of that response part of that fire alarm pulling is TNF And so if you haven't heard of these cytokines are essentially text messages to your homeland security saying we need inflammation now We're preparing for a skirmish And so we don't measure TNF in the clinic We usually track lupus with things like CRP ESRs blood counts and compliments which are all Distilled the TNF But there are a few drugs that target TNF which is which will return to in a moment here because I think it adds to the story in an interesting way And so a plasmodium infection TNF What we've learned about TNF is it's not just a trigger for inflammation, but it also plays an immunoregulatory role And so you've got two specific arms of your specific Immune system your th1 and th2 and it seems that the autoimmune diseases that are characterized one of the autoimmune diseases that seems to be characterized by th2 preponderance is lupus And so you have the infection you get the TNF th1 preponderance and it seems to quiet the disease and so the idea is that West Africans have these polymorphisms and TNF genes that were selected for by Malarial infection that protect against SLE And so we we use TNFs in rheumatic patients who have diseases where TNF seems to be a big player in Activating the immune process and rheumatoid arthritis is is a big one and Then a category of the diseases that we call seronegative spondyloarthriopathies. So this includes psoriasis psoriatic arthritis Crohn's ulcerative colitis Ankylosing spondylitis. These are all HLA B 27 associated disorders and blocking TNF here seems to do a really good thing and in a lot of cases the results are miraculous and You see in the commercials the glowing smiley elderly woman who's doing back flips and cartwheels and beating her husband at arm wrestling She doesn't have synovitis anymore In part there's these drugs like humera and burl and remiccate to thank But what's interesting is that they can actually trigger lupus? Okay, so you're blocking TNF and we mentioned TNF's immunoregulatory role So I got to share this case with you that I learned about from this rheumatologist I was listening to and he had this lady come out from Greece who was told she had ankylosing spondylitis by one of the best rheumatologists she's ever seen and She comes in demanding remiccate because that's the biologic agent that she was getting before and so before he writes her prescription for that he wants to see some evidence that she actually has Ankylosing spondylitis and so she hands him a bone scan and she says see I have Ankylosing spondylitis and he looks at her bone scan and starts chuckling and he says lady those aren't your SI joints Those are your kidneys and so apparently the previous doctor who had saw her Said that her kidneys were her sacroiliac joints and was treating her with Remiccate and that wasn't indicated for and so what ended up happening When he worked her up further was he found that she actually had She had fibromyalgia which she treated differently, but she was developing a lupus-like syndrome That was due to her being on this TNF agent So he holds the remiccate And her antibodies and her symptoms get better and he treated her fibromyalgia with lunesta which improved a lot of her symptoms And so it goes back to what we spoke about before Described in this review on anti-TNS induced by lupus, williams and friends Described this cytokine shift hypothesis that proposes the pharmacologic systemic blockade of TNF alpha Suppresses production of th1 cytokines Thereby driving the immune responses toward th2 il-10 and interfere on gamma and so downstream of these events are lupus And I try to find some data on the incidence of this phenomenon in caucasians versus African-americans, but there isn't there isn't enough out there right now And so to recap Uh, you're now lupologists lupus is a multi-system autoimmune disease with protean manifestations It can be more limited or it can be really mean and nasty And the genetic predisposition for lupus may have been selected for by a plasmodium infection With a potential pathway for explanation being through TNF alpha And those TNF antagonistic therapies have the potential to induce lupus like syndromes And so some implications of this may be up regulating TNF in some way Using immunoglobulins produced during plasmodium infection Uh, we I didn't really talk about nitric oxide too much, but part of the TNF response and and maybe, uh Taking advantage of that pathway and then there's different herbs and botanicals that skew towards uh th1 preponderance for your specific immunity And so, uh mosquitoes I There's there's ideas out there about treating certain diseases with uh different infections and I don't know if well ever be there With malaria, but but who knows I think that antibody idea is kind of attractive, but uh Being a nature path I wanted to kind of give you some Points on some things to integrate into the standard of care that that we do in practice and so um Obviously heavy emphasis on diet and lifestyle And I don't know if uh, you had a chance to listen to rob abbott angiolton And mickey tress got speak, but we use the autoimmune paleo protocol in practice And I've seen outstanding results with it across different autoimmune diseases So that or some other kind of elimination diet to implement identifying pathogens in the gut um low-dose naltrexone quinocrin adiabrin and chloroquine a lot of people give up on plaque when they're too early because of sensitivity There's these other avenues here to try out and then anesthetal cysteine All right, so that's what I've got Thank you for being here and I'll take any questions now No questions I was just wondering about uh Some of the mechanisms involved in some of the things that you're You're using with your patients. So you're obviously talking about tnf uh tnf alpha Is that you know something that we should really be targeting? I'm sort of I'm thinking about exercise, you know Exercise if you exercise very intensely you increase tnf alpha, but even at lower levels you're suppressing tnf alpha production, right supposed to be suppressing You know chronic inflammation like how how does that feed into this is tnf really sort of like the crux of the matter Or is it more upstream than that? Yeah, I I don't I don't know how that would relate really to exercise I don't know if the exercise is really going to influence tnf alpha in a big enough way for that to be relevant and then you know in terms of exercise it used to be really gung-ho about getting people to Exercise more aggressively but with these patients and their functional status You got to be really careful and so most of them are just doing light exercise and walking and You know got to be mindful of them being outside as well because of photosensitivity and the tendency for sun to set off their disease, but Yeah, uh, I think where the tnf alpha is most relevant right now is is with these therapies that you're considering to control the disease and The potential to induce a lupus-like syndrome from that Thank you for That really I think interesting talk. I was curious you Kind of were alluding to some of this In the talk, but if you wanted to expand a little bit more about maybe some of the practical Things that you know, you're doing sort of integrating your mindset with the clinician you're working at I'm definitely interested it's coming from more No traditional perspective and trying to bridge those worlds But if you wanted to expand a little bit more about some of the things that you're doing And bringing your expertise alongside the sort of more traditional rheumatology I thought that would be a really good thing to talk about Yeah, so my big focus is on is on the gut and And the lifestyle so so I mean there's a lot of different levers we can pull and and it goes back to those stochastic events we talked about and heavy metals and toxicants and and And dysbiosis and nutrient sensitivity and things like that. So basically what I'm doing Is is really hitting hard with the dietary therapy and then seeing what's going on in the gut and I just was a little bit Rattled by lucy mailings presentation and some of the Strategies that I've been using so I'll have to rethink things there but I've really seen a lot of benefit for patients in Addressing some of the simple things that appear on some of these Digestive studies and yeast seems to be a really common one And so, you know, I use a lot of diflucan and nice statin Lodos naltrexone, so there's a rheumatologist on the east coast His name is Andrew share beam And he's using it in a way that's a little bit different from what I was taught from some of our functional mentors and so I usually like to start that at 0.5 and slowly work that up to as high as 12 milligrams in some cases And then I'll sometimes I'll take the reins on the anti-malarial prescription A lot of rheumatologists out there aren't Going beyond plaque when all but sometimes the patients can get a better response from quinocrine. I don't like chloroquine so much because you have to Pay close really close attention to their eyes more than you do with plaque when all but sometimes Switching the anti-malarial to quinocrine can sometimes give them a really good response And then an acetyl cysteine so That's uh, I usually use that anywhere from 6 to 2.4 Grams and and that's kind of also a disease modifying agent I have a question about early detection Lupus seems to be one of the autoimmune diseases that people struggle a lot with getting a diagnosis and Actually probably making that diagnosis is pretty tricky. There's a lot of different things that people can present with So i'm just curious What you would recommend as far as things for people to look out for Maybe for especially the those of us who are more health coaches or allied Practitioners who are maybe not making the diagnosis but things that we would maybe notice in our practices and then The testing that we can encourage our clients or even like our friends and family members to go to a doctor and Get those tests for that early diagnosis so that they can avoid that rapid progression of the disease Yeah So That's a really great question And it's really hard to detect early on but the biggest thing that I would say are constitutional signs And so these are symptoms that the body expresses when inflammatory cytokines are floating around and they consist of things like fevers weight loss night sweats loss of appetite Kind of like flu like feelings and the key is that they will come and go And with this cadence they can persist anywhere from A few days to a few weeks so so that's that's probably the biggest key More specific signs may not appear That early and and so when I say more specific signs Some of these the characteristic rashes on the face like the malar rash small joint involvement Kidney involvement where they're urinating blood or maybe they're noticing some funny urine abnormalities Those are those are probably the big ones but early on looking for those constitutional signs and then in terms of lab testing That's a tough area for me You know because the way the way rheumatology is right now A lot of the rheumatologists out there are really conservative and they would be hesitant to diagnose just based off of you know Those those signs and even if you had a bit more of those specific features I think a lot of folks are still going to have a hard time in terms of diagnosis, but There's a there's a panel I use called the The vis by exigen diagnostics and and it includes a lot of these these markers for lupus and other potential overlapping autoimmune diseases Thank you. Mm-hmm. Thank you. Uh, everybody a round of applause applause for dr. Mitchell. Thank you