A Case of Friendly Fire
Our modern lifestyle is great in many ways, but it isn’t without its drawbacks. We are being exposed to an ever-increasing toxic milieu of chemicals, pathogens, physical stress, mental stress, toxins, and genetically- and hormonally-modified foods.
Not coincidentally, the incidence of autoimmune disease has nearly tripled over the past few decades. Though we can’t pinpoint the causes, one thing is clear: this toxic milieu is having an effect.
Autoimmune diseases occur when the immune system loses the ability to differentiate between self and non-self, resulting in a misguided attack on your body. There are at least 80 known autoimmune diseases and each is different depending on which tissue the body attacks. Rheumatoid arthritis (RA) is the immune system attacking your joints. If the body is attacking certain connective tissues, that is lupus.
The development of an autoimmune disease requires two mistakes: an initial priming event, and a subsequent promoting event by the immune system. We are not sure yet what triggers these mistakes, but evidence is mounting that chronic, low-level inflammation is one important factor. Chronic inflammation—even mild inflammation—is believed to be a significant trigger not just for autoimmune diseases, but also for heart disease, type 2 diabetes, and cancer.
A case study
A 17-year-old, very thin male with Asperger’s and autoimmune vasculitis (where the immune system attacks blood vessels) came to see me for abdominal pain, right thigh pain, and headaches. He was very withdrawn, responding with only yes/no answers. His mom and dad were with him and answered most of my questions.
His symptoms ranged in intensity depending on the day. He had missed some school, avoided social activities, and was generally down. He had been to several doctors, including a rheumatologist, and had been prescribed plaquenil, prednisone, and a couple of other medications that had no effect and were quickly abandoned. His dad, a physician himself, felt none of the doctors knew what was wrong with him and were just trying to offer him something.
It was obvious that this patient had multiple symptoms related to stressors on his body, an unbalanced gut, and inflammation. To get him better, we needed to decrease his body stressors and inflammatory triggers, and heal his digestive tract. This brings us to the crossroads of the digestive tract and the immune system, an intimate relationship that deserves closer inspection.
Locating the immune system
When I first heard that 70 percent of my immune system was in my intestinal tract, I was quite surprised. The medical term for this is GALT, or gut-associated lymphoid tissue. I had assumed that my immune system would be concentrated around my heart, brain, eyes, and so on. It’s protecting my vital organs, so I thought it would be concentrated in these areas accordingly. It seemed odd to me to have such a high percentage in the intestinal tract. So why is almost my entire immune system in my gut?
In trying to understand this I drew a simple picture of the human body and realized something interesting. On closer inspection, the intestinal tract is actually open to the external environment. Something in the mouth is not technically in the body until it is absorbed. Our intestinal tract is actually an external environment—albeit an internal, external environment. If you swallow a penny (yes this happens from time to time, ask any pediatric emergency physician), the penny never actually enters the body. Rather it is surrounded by the intestine and is in this internal external environment temporarily.
The human intestinal tract has a massive surface area. For reference, our skin has the surface area of a bed sheet, our lungs have the surface area of a tennis court, but the intestinal tract—stretched out and flattened—would have the surface area of a football field.
It is vital for our health that we protect against toxins, bacteria, parasites, viruses, and other potential invaders crossing this border and entering our body. Since the intestinal tract is the barrier, it makes sense that the immune system is so prominent in the intestinal tract. We are breathing in and ingesting toxins and bacteria with every breath and every meal, and this large absorptive surface needs an army at the ready to attack anything harmful that crosses and tries to enter the body.
As we said above, the immune system’s goal is to distinguish between self and non-self. Millions of cells in the immune system and antibodies in our body are constantly bumping into proteins and other molecules in circulation. They very quickly recognize these as self or non-self. The rules are simple: if it is self, leave it alone. If it is non-self, kill it.
This system is generally very good at proper recognition. But what happens if there is a mistake, and what situations render that more likely?
A case of mistaken identity
Let’s say we have some microscopic injury or area of inflammation in the gut. It could be microtrauma from ingested food or the result of a mild viral or bacterial infection. Whatever the case, this small area of inflammation may cause a local increase in gut permeability (or leaky gut), allowing a larger-than-appropriate food particle to cross the basement membrane of the intestines and enter the local bloodstream.
The immune system is right there and ready to respond. This abnormally large food particle might be treated as a foreign body by the immune system, so you make an antibody against that food resulting in a food sensitivity. That, however, is not the biggest problem.
The reaction itself causes the release of local inflammatory mediators that trigger another reaction, which may lead to more “leaky gut” and more large food particles crossing into the blood. This cycle can end in a state of chronic low-level inflammation in the gastrointestinal tract. Remember, this is a football field-sized organ that is now inflamed. If you get a football field-sized organ angry, you are not going to thrive, to say the least.
With this massive barrage of GI inflammation and antibody production, the odds of a case of mistaken identity increase greatly. If that happens, an “autoantibody” is produced that incorrectly identifies self as non-self. Autoantibodies trigger inflammation against your body tissue.
A simple blood test can detect these antibodies. The appearance of these autoantibodies is the first step in the development of autoimmune disease. The most common autoantibody is called ANA, anti-nuclear antibody. This nonspecific autoantibody is a warning sign that the immune system has been primed. If another similar mistake occurs, there is a high likelihood that the person will develop an autoimmune disease.
The tipping point
So here’s the big question: which autoimmune disease will they develop? That depends on what the second mistake is. If that autoantibody falsely identifies a joint, we call that rheumatoid factor. A positive ANA plus a positive rheumatoid factor equals rheumatoid arthritis. If the second mistake is against certain connective tissues we call it scleroderma, or lupus. If it is thyroid, we call it Hashimoto’s thyroiditis, and so on.
Why do some people develop autoimmune disease while others do not? How do we account for times when the same underlying pathologic process is at play, yet leads to very different clinical presentations?
We all have unique weak spots genetically and we all have slightly different environmental influences. You may be prone to eczema, irritable bowel, or Crohn’s disease, while I may be prone to ulcerative colitis, depression, or an autoimmune disease. The challenge for physicians lies not in identifying these differences, but rather in identifying the pathologic process that triggers each person’s symptoms. This is a key point, and this is where I feel my traditional training failed me.
Many times patients have come to me with arthritis, saying, “My doctor tested me for rheumatoid arthritis and I am ANA positive, but my rheumatoid test [rheumatoid factor or RF] was negative.” They were told that it might be rheumatoid arthritis but it is too early to say for sure. The doctor planned to check the RF level again next year. In the meantime they were usually prescribed anti-inflammatory medications to treat their symptoms.
A fire starting
This is problematic, to say the least. A positive ANA is a warning sign akin to smoldering embers. In someone with a lot of arthritis symptoms, a positive ANA and negative RF tell me the fire is kindling. Waiting for the fire to gain ground and show up as a positive RF so you can then prescribe powerful and dangerous medications that do nothing to stop the underlying problem is the wrong approach. These medications are fraught with dangerous potential side effects including cancer and “infections that may lead to death.” (You’ll see this if you read the inserts that come with the prescriptions.)
Let’s return now to our case study, a 17-year-old male with Asperger’s who came to see me for abdominal pain, right thigh pain, and headaches. He had been to several doctors, including a rheumatologist, who believed he had autoimmune vasculitis. The doctor had recommended plaquenil, prednisone, and a couple of other medications that had no effect and were quickly abandoned.
The patient had missed some school, avoided social activities, and was generally down. I tested his IgG food sensitivities via a blood test, not the pinprick test the allergist usually does. These are the antibodies that can be produced via the leaky gut and inflammation mechanism I described earlier. I was looking for signs of systemic inflammation. It turned out he had over two dozen of these types of food sensitivities/allergies. We also performed a digestive stool analysis which showed that two different strains of candida (yeast) had colonized or lived in his gut. He had almost no beneficial bacteria, several nonspecific inflammatory markers, and some malabsorption. His hair analysis showed his body stores of some essential nutrients were very low.
We treated all of this with dietary restrictions, antifungal medication, herbal antifungals, probiotics, L-glutamine, nutritional IVs, and a few other nutrient and mineral replacements orally. I use L-glutamine and some combinations that include this amino acid, including nutritional IVs to help repair the intestinal mucosa. This way, when we give the probiotic there is a healthy surface for them to attach to. I like nutritional IVs because there is no question of absorption, the nutrients are immediately available, and we can often use larger doses because there is no risk of GI upset.
When I saw the patient about two months later, his dad came in beaming. I asked the young man how he was doing. This previously closed-off, shy, extremely introverted young man began to tell me at length how embarrassed he was when he lost his retainer at school by throwing it away on his lunch tray and had to dig through the trash in front of his friends. I had to ask myself “Who is this guy in front of me?”
This was not the same shy guy I met two months ago—this was a completely different person. He was upbeat, jovial, smiled, and made direct eye contact. He had not done this the first couple of visits. His leg pain, abdominal pain, and headaches were gone. He was happy and his mom and dad were thrilled.
Why did he get better? What was the key? There really is not just one answer to the question. He got better because we helped calm his immune system down by reducing the total load of stressors to his body, helped his gut heal, decreased his inflammatory cascade, and replaced his nutritional deficiencies. I think this decreased the likelihood for him to develop one or more autoimmune conditions. He suffered from multiple food sensitivities, dysbiosis (bad bacteria) in his gut, as well as candida.
Even though he is better now, I believe that he has the potential to develop an autoimmune disease. I also believe that it is within his power to avoid it. He is vulnerable to headaches, abdominal pain, the development of food sensitivities, and apparently, irritation of nerves in his right thigh. (Remember his leg pain or “autoimmune vasculitis?” I now feel autoimmune vasculitis was an incorrect diagnosis, or at least premature.) Regardless, we took the right steps and he got better. The other good news is that he now has the tools and understanding to prevent these symptoms.
It can be said that every patient is their own clinical trial: no matter what the results are, they are 100 percent statistically significant for that patient. I strongly feel that individualized medicine, which is what you saw described above, is the next step in the progressive evolution of medical care. It is not “alternative medicine” to me. It is “sound, evidenced based, individualized, preventive, natural, and nutritional medicine.”
That particular specialty has not been invented yet, unfortunately.
In a bit of irony, although I am treating the individual, I can apply the same principles of treatment to every patient. So the good news for me is that even if I am not sure why a patient is suffering symptoms—or even what their actual diagnosis is—I can apply sound principles of medicine and logic. When I do this people often get better even if I don’t always know the exact reasons why. I may not always know why you got better, but if I know that you got better, sometimes that’s good enough.
If you have been diagnosed with an autoimmune disease or if your doctor has been suspicious enough to order the tests, some of what I described above may be occurring in your body. It is important that you find a physician that understands and treats the underlying causes of your symptoms, not just the symptoms themselves—remember, you don’t just want to feel better, you want to be better.
Jeffrey Hendricks, MD, has practiced emergency, occupational, family, alternative, and integrative medicine. He has served as medical director for Shoreline Occupational Medicine, Bosch Automotive Corp, Shoreline Alternative and Integrative Medicine, and Biogenesis Medical and Wellness Centers. He is a triathlete, inventor of RIZE health drink, and CEO of Nothing Ventured, LLC.
Naltrexone is a drug used for its powerful anti-opioid receptor effects. It traditionally has been used in the treatment of opiate addiction and overdose. I have used it many times in the emergency room to treat heroin overdose and have witnessed its incredible power. Its effects can be so dramatic that just before giving it to an overdose victim, I make sure there is help immediately available. A lifeless, not-breathing, seemingly dead patient given 50 mg of Naltrexone can not only come back to life in a matter of seconds, they can be physically combative and very strong. They are often angry and combative because the treatment that just saved their life also put them into a state of immediate withdrawal.
It turns out that this powerful life-saving drug has other benefits at just a fraction of the normal dosing (4.5 mg as opposed to 50). LDN, or low-dose naltrexone, appears to have important effects on immune system function. The exact mechanism is still being elucidated but there have been good studies demonstrating that it is relatively safe.
Usually given at bedtime, naltrexone is believed to trigger upregulation of endorphin production during a critical period of sleep. We do know that it upregulates the activity of certain cells called natural killer T-cells, a benefit to HIV patients. It has shown efficacy in protecting the immune system from deterioration in some studies of HIV patients. It also can downregulate the overactivity or misguided activity of the immune system in autoimmune disease. Based on the fact that LDN seems to benefit two seemingly opposite immune system problems—i.e., deficiency and overstimulation—it is possible that LDN acts as an adaptogen. An adaptogen is a molecule that can upregulate a system that is low, and can downregulate a system that is overactive.
While we work out the details of just how this process occurs I would argue this: most drugs treat symptoms and do not correct the underlying problem. A drug that can serve as an adaptogen has the potential to normalize otherwise abnormal physiology. If we can achieve complete and sustained normal function in a previously strained, diseased system, the word we use for that is “cure,” a term used all too infrequently in medicine today.
An excellent resource for more information is lowdosenaltrexone.org.