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Where to Start with Lyme or Mold... Herx Reactions & More

Today, we are talking about Herx reactions, which is a bit niche but considering that in treating many chronic illnesses/infections, there is typically an initial die-off or toxin release that can initiate this so-called Herx reaction.

So to start out, what is a Herx reaction? Basically, The Herxheimer reaction manifests as an acute exacerbation of existing symptoms or the onset of new symptoms shortly after the initiation of antimicrobial therapy. It typically occurs within hours to days of treatment initiation and is often self-limiting. Common symptoms include fever, chills, headache, fatigue, and exacerbation of skin conditions.

Now, The underlying mechanisms driving the Herxheimer reaction are multifaceted and encompass both host immune responses and microbial factors. So now, let’s dive into these causes just a little bit more. So if we start on the microbial side of things, we could first address the release of endotoxins. And for reference, let’s just take Lyme disease as the example condition that we analyze in order to evaluate how a Herx reaction occurs. Okay, so the release of endotoxins… So essentially Upon antimicrobial treatment, the rapid bactericidal action leads to the lysis of the spirochete bacteria called Borrelia, the causative agent of Lyme disease. And since Borrelia is a Gram-negative bacterium, its cell wall contains lipopolysaccharides (LPS), which are potent endotoxins. So basically, The disruption of bacterial cell integrity during lysis results in the release of these endotoxins into the surrounding environment, including the bloodstream.

Now: The presence of LPS in the bloodstream can trigger a cascade of inflammatory responses orchestrated by the innate immune system. For example, LPS binds to Toll-like receptor 4 (TLR4) on immune cells, such as macrophages and dendritic cells, which can lead to the transcriptional upregulation of pro-inflammatory cytokines, notably tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β).

So to recap everything so far, we’ve got Borrelia dying, LPS being freed, and that freed LPS endotoxin can bind to TLR4 on immune cells like macrophages or dendritic cells, and then, those cells can increase their transcription of pro-inflammatory cytokines.

Okay, so now TNF-α, IL-6, and IL-1β can then propagate the immune response by promoting vasodilation (which widens blood vessels, increasing blood flow to the site of infection or tissue damage), increasing vascular permeability (this allows immune cells and proteins to pass more easily from the bloodstream into the affected tissues, aiding in the defense against the pathogens.), and the cytokines themselves can actually also signal the recruitment of other immune cells, such as neutrophils and monocytes (which are capable of differentiating into those macrophages and dendritic cells we talked about earlier)… So all in all, we’ve got these pro-inflammatory cytokines increasing and propagating the immune response via vasodilation, vascular permeability, and immune cell recruitment.

Now in addition to all of that, the pro-inflammatory cytokines can also stimulate what is called the acute-phase response, leading to fever, chills, and systemic manifestations characteristic of the Herxheimer reaction. For example, when these cytokines interact with the hypothalamus in the brain, Fever is induced, resulting in an increase in body temperature, which helps to inhibit the growth of certain pathogens and enhances the activity of immune cells. So now we’ve got a propagating immune response plus the induction of the acute phase response which is inundating your body with symptoms.

So far we’ve talked about how the antimicrobial treatment kills the bacteria and releases bacterial remnants including LPS endotoxins… so what happens now that we’ve got all of these bacterial remnants and debris in the body… here is where the phagocytic immune cells like macrophages and neutrophils step in.

Starting off with macrophages: we remember that Macrophages are professional phagocytes capable of engulfing and digesting microbial pathogens and cellular remnants. And, after phagocytosis of these microbial remnants, the macrophages then process and present antigens derived from the engulfed material to immune cells called T cells (and these t cells are part of the adaptive immune response… so we are switching from innate to adaptive here). And through this process of engulfing the bacterial remnants, the macrophages release cytokines such as interleukin-12 (IL-12) and interferon-gamma (IFN-γ). These will then promote the activation and differentiation of the T cells; AND, this activation and differentiation of t cells is critical for coordinating the adaptive immune response.

Now before we fully switch gears to the adaptive immune response, we have a few other phagocytic immune cells like neutrophils that serve to play a role as well… so like I just said Neutrophils are another type of phagocytic cell that plays a prominent role in the early innate immune response to bacterial infections. Neutrophils are recruited to sites of infection or tissue damage, where they engulf and destroy microbial pathogens through phagocytosis just like those macrophages… So overall, the activation of these phagocytic immune cells such as macrophages and neutrophils are essential steps in the innate immune response to bacterial infections, and this process is what eventually leads to the initiation of the adaptive immune response like we briefly just mentioned.

Now, to highlight the difference between the innate and adaptive immune responses just a bit more, we need to remember that the adaptive immune response is highly specific, meaning it targets specific antigens presented by pathogens. This specificity is achieved through the diversity of T cell receptors (TCRs) and B cell receptors (BCRs), which can recognize a vast array of antigens. And In contrast, the innate immune response recognizes broad patterns shared by many pathogens. And of course, the immune cells that are involved are certainly different. In the innate or first-acting immune response we have those cells like the macrophages and neutrophils working diligently to phagocytize the bacterial remnants and then present them to T cells for the purpose of activating and differentiating those t cells. And in the adaptive immune response we have those cells like the T cells and even B cells that are antigen specific and even produce antibodies in response to the antigen presentation. Also, what is important to note is that due to the specificity of the adaptive immune response (meaning that it is specific to the antigen), we can say that the adaptive immune response has immunological memory, so upon re-exposure to the same pathogen, the body is able to recognize it and launch an attack even more efficiently. So all in all, while the innate immune response is adept at recognizing and eliminating pathogens through phagocytosis and inflammation, it’s often not sufficient for clearing the infection totally, and some pathogens can even evade or subvert innate immune mechanisms which just places even more authority in the hands of the adaptive immune response.

So with that said, here’s the issue: what happens when the adaptive immune response is not launched efficiently and appropriately? Well, we often see chronic infection and or inflammation. And biochemically speaking, what we are talking about is a disruption in antigen presentation to the t cells. So if you remember from a minute ago, we talked about how those macrophages engulf the bacterial remnants left over after the antimicrobial treatment kills the bacteria and then present proteins to the t cells in order for the t cells (and therefore the adaptive immune response) to become activated. So basically what I am saying here is that if the genes that encode for these proteins contain certain polymorphisms, this antigen presentation can become disrupted and the adaptive immune response can be held up quite significantly. Therefore, we get chronic inflammation as a result of the failure of the adaptive immune system to fully clear the pathogenic bacterial remnants. This is truly the crux of what we call biotoxin illness or chronic inflammatory response syndrome.

Also, this is why a genetic test is very helpful when it comes to ensuring how your HLA genes are affecting your immune response.

So if we go back to the case of a Herx reaction and to summarize everything thus far: say we have Lyme disease, we take cats claw or undergo another antimicrobial treatment, the antimicrobial begins to kill the Borrelia spirochete bacteria, and the LPS endotoxins in the cell walls of the bacteria are released rapidly into the bloodstream. Then, the innate immune response goes crazy and initiates vasodilation, vascular permeability, and pro-inflammatory cytokine production to recruit more of these innate immune cells. And here, we also see the acute-phase response ensue – so think fatigue, fever, aches, flu-like symptoms essentially. Now, these phagocytic innate immune cells begin phagocytizing the bacterial remnants left over from the antimicrobial treatment, and assuming a good HLA gene pool (which is not present in those with CIRS), the innate immune cells then present these remnants in the form of little proteins to the T cells in order to initiate the adaptive immune response and fully clear the pathogen.

So with all of that said, when we think of the Herx reaction, we are thinking about a pretty potent inflammatory response carried out by the innate immune system. So basically, we get this uncontrolled activation of immune cells and the excessive release of cytokines that culminate in a cytokine storm, characterized by overwhelming inflammation and tissue damage. This dysregulated immune response can then lead to systemic manifestations, including hypotension (remember how we said that vasodilation occurs in order to get those innate immune cells to the site of infection), we can also see organ dysfunction, and even multi-organ failure due to all of these inflammatory cytokines swirling around as a result of the innate immune system's activation!

So a couple of things here: first, it goes without saying to always work with a doctor. Second when starting an antimicrobial treatment for something like Lyme, you need to prime the body in order to better handle the sudden onset and release of endotoxins like LPS into the bloodstream. Third, and beyond the scope of the Herx reaction, you need to address any HLA gene defects in order to obtain clearance of the pathogen. We will talk about that third point more specifically in a later post. For now, let’s focus on addressing some of the ways we can mitigate the Herx reaction when first beginning an antimicrobial treatment in the presence of chronic infection such as Lyme or mold. I will say, though, that in mitigating the Herx reaction and in addressing the HLA gene defect, some of the strategies are the same… such as the use of specific binders. But with that said, for the Herx reaction… what can we do?

First, when it comes to Herx reactions, the important thing to keep in mind is that the body is herxing because it is pretty toxic right now. That is the sign to slow down and titrate the antimicrobial therapy. In other words, Slowly titrating antimicrobial treatment to gradually reduce the bacterial load and minimize the intensity of the Herxheimer reaction. So starting with lower doses and gradually increasing over time allows the body to adjust to the treatment and may reduce the severity of symptoms.

Another thing we can do is address the inflammation. Now, it’s important to note that inflammation is essential for signaling the immune response and fighting off pathogens, but excessive inflammation can cause collateral tissue damage and exacerbate symptoms. And often, we have excessive inflammation in these cases, so reducing inflammation in the body is typically very advantageous for reducing the symptoms of a Herx reaction. So, what are some of those ways to reduce the inflammation? Some supplements include: omega 3s (SPMs derived from fish oil can be super helpful), Curcumin, Quercetin, Resveratrol, Green Tea Extract, Boswellia, and Ginger… there are some others, but those are some helpful ones.

Okay, next… supporting the body’s clearance pathways: supporting the liver, lymph, and kidneys. I’ve talked about these in-depth in previous articles, but in general, some liver support supplements include milk thistle, DHM, artichoke, calcium D glucarate, liposomal glutathione, NAC, amino acids like glycine and taurine. Supporting the lymphatic system through echinacea, cleavers, calendula, and some others. Then, supporting the kidneys with things like nettle, marshmallow root, parsley, and some others.

Also, when it comes to Herx reactions, ensure you are using the restroom! There is no use in doing anything else if you are not eliminating properly.

A few other things: taking Epsom salt baths and taking supplemental binders. Some binders include activated charcoal, chlorella, bentonite clay, zeolite, and of course, cholestyramine (we will get into these in a later post when we are talking about the best binders for which types of toxins and also addressing the ways to mitigate the HLA gene defect and fully clear the pathogens).

So, all in all, binders, anti-inflammatory supplements, liver + lymph + kidney support, epsom salt baths, and of course taking things slowly can all be super helpful when encountering a Herx reaction during antimicrobial treatment for something like Lyme or mold.

-- Always work with a licensed physician --


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