Immune Compromised - 028

Digging deeper and finding answers

In the last newsletter, I wrote about how my prostate-specific antigen (PSA) had almost doubled from 63 to 117 in three months - May 2023 to August 2023. A fast doubling time portends a poor prognosis and a higher likelihood of developing metastases.

From March 2022 to May 2023, I had gotten my PSA doubling time to slow to 25.3 months. This timeframe included my proton therapy, lasting from January 10, 2023, to February 24, 2023.

But then strange things began to happen. The week before I was supposed to start proton therapy, I had a bout of COVID-19, my second bout since being vaccinated and boosted. That delayed the start of proton therapy as we pushed it back a week.

Proton Therapy

I developed side effects during proton therapy, including severe fatigue, nausea, and constipation. I was prescribed Zofran for nausea, which worsened the constipation. Switching Zofran to Compazine helped the nausea and reduced the intensity of constipation but didn't eliminate it.

I have rarely experienced constipation before this, especially the severe constipation I experienced during proton therapy. Upon completing proton therapy, the constipation improved but never quite fully resolved. Then, I began having bloating with abdominal distention and excessive flatulence.

Some days, the distension is so bad my stomach looks like I'm five months pregnant. I also have intermittent abdominal cramping. One of the strangest things I've developed is burping as soon as I get out of bed in the morning.

These symptoms persisted, and the fatigue worsened. In retrospect, it wasn't a good idea to begin proton therapy before fully recovering from COVID-19. COVID-19 suppresses your immune system, and it didn't help that my proton therapy focused on "microwaving" the lymph nodes in my abdomen.

Healthy lymph nodes are essential to a healthy immune system. Despite proton therapy being more focused than traditional radiation, it is not without collateral damage.

The parts of my body I suspect experienced collateral damage include my intestines, gut-associated lymphoid tissues, and enteric nervous system - my gut's brain. This collateral damage will come into play later in putting all the puzzle pieces together about why my immune system became compromised.

Skin Cancer

In late March, about one month after completing proton therapy, I underwent an excision of a suspicious skin lesion on my chest that rapidly grew during proton therapy. The pathology turned out to be an aggressive squamous cell carcinoma.

When I returned for the biopsy results, my dermatologist told me she only sees that type of skin cancer in transplant patients. That cued me into the idea that my immune system is significantly compromised.

Sore Throat and Fatigue

In early June, I developed a month-long sore throat and saw an otolaryngologist (ENT) who scoped my nasopharynx and said he couldn't see anything wrong. He attributed my symptoms to gastroesophageal reflux. I know what reflux feels like, and I had not been having those sensations.

It was about this time I told my colleague and close friend, Dr. Daniel Kessler, about what had been going on. Daniel is one of the most intelligent physicians I know and is board-certified in multiple specialties, including Family Medicine and Functional Medicine.

He recommended blood, urine, and stool testing to help determine why my immune system is compromised. Daniel approaches patient care holistically. He doesn't focus just on alleviation of symptoms but looks for root causes of illness in an attempt to intervene there.

Blood Testing

We started with blood work, which showed no abnormalities except for elevated antibodies to the Epstein-Barr virus (EBV). EBV is a member of the herpes family of viruses, and once you are infected, it stays dormant in your body for life unless it reactivates.

EBV causes mononucleosis, a contagious illness typically occurring in young adults known as the kissing disease. It can reactivate under stress and cause symptoms such as sore throat and fatigue.

It's very similar to how the chicken pox virus, a member of the herpes family, stays in your body for life and can reactivate as shingles. Both viruses reactivate when the immune system weakens. Once reactivated, EBV causes further weakening of the immune system by infecting B lymphocytes and hindering their ability to function.

I found an excellent scientific article on the causes of EBV reactivation, and recently, I had two of them - COVID-19 and radiation (proton therapy). There is another cause of EBV reactivation, which urine testing also showed I have, but I'll save that for later in this article.

Stool Testing

Due to my persistent gastrointestinal (GI) symptoms after proton therapy, Daniel ordered a GI effects stool test by Genova Diagnostics. It is a comprehensive stool analysis that looks for markers of digestion, absorption, inflammation, immunology, and the status of your microbiome - microbes in your stool.

This stool test revealed several remarkable findings, including:

• Undetectable pancreatic elastase

• Very high levels of Beta-glucuronidase

• Low short-chain fatty acids

• Low beneficial bacteria

• High levels of E. coli

• High levels of a potentially pathogenic bacteria called Klebsiella pneumoniae

The pancreas releases pancreatic elastase, which is a measure of how well the pancreas produces and releases digestive enzymes. The pancreas releases enzymes by communicating with the small intestine. When the small intestine lining is damaged, that feedback loop signaling the pancreas to release the enzymes can be lost.

If your pancreas doesn’t release digestive enzymes well, known as pancreatic exocrine insufficiency, you can develop malabsorption of nutrients and malnutrition. In addition, many studies correlate pancreatic exocrine insufficiency with small intestinal bacterial overgrowth (SIBO).

Beta-glucuronidase is an enzyme produced by pathogenic bacteria, and high levels reflect adverse metabolic activity in the intestines. High levels can limit the excretion of compounds from the body, such as carcinogens, estrogen, and fungal toxins - mycotoxins.

Short-chain fatty acids feed colonocytes, the cells lining your colon. Mine must be starving.

Small Intestinal Bacterial Overgrowth

I also had high levels of a microbe called Methanobrevibacter smithii, a methane-producing bug commonly found in intestinal methanogen overgrowth, which includes methane-dominant small intestinal bacterial overgrowth (SIBO).

Even though we didn't do a breath test looking for high methane levels, everything pointed to SIBO. There are different types of SIBO, depending on which gas is in the breath test - hydrogen or methane.

Overgrowth of E. coli and Klebsiella pneumoniae are culprits in hydrogen-dominant SIBO, and Methanobrevibacter smithii is the main culprit in methane-dominant SIBO. It appears I have a mixed bag causing my SIBO.

SIBO is a condition that causes increased intestinal permeability, also known as leaky gut. The increased permeability of the cells lining the intestines occurs at a molecular level. Still, there is enough leakiness that proteins and toxins from microbes leak through into the gut-associated lymphoid tissue (GALT) and bloodstream.

Once these proteins and toxins leak into the GALT, your immune system is on high alert and reacts to these invaders by creating inflammatory cytokines. If it continues long enough, the inflammation becomes systemic, resulting in fatigue, muscle aches, joint pains, headaches, and autoimmunity.

The collateral damage my proton therapy caused possibly includes damaging the lining of my intestines, my GALT, and my enteric nervous system. Damage to the enteric nervous system can damage the migratory motor complexes that keep your small intestines moving smoothly, also known as peristalsis.

One of the key contributors to developing SIBO is impaired peristalsis of your intestines. As peristalsis fails, the microbes in your colon start to back up into what should be a relatively clean microbial environment of your small intestines. Thus, the origin of the term "small intestinal bacterial overgrowth."

In addition, the lymph nodes draining my gut-associated lymphoid tissue took the brunt of the proton therapy, so they were damaged, which likely resulted in immune system dysfunction.

That's the sad part about most cancer therapies. Your doctors use tools and drugs to save your life, but damage occurs to your body.

To top it off, the methane produced by Methanobrevibacter smithii causes constipation and bloating. It's a vicious cycle that sets up, making it difficult to treat.

Urine Testing

Let's move on to what we found in my urine, which probably represents the most significant reason, other than EBV, for causing me to become immune compromised. We checked my urine for mycotoxins, which are toxins produced by funguses.

When exposed to fungal overgrowth in a water-damaged building, you can see mycotoxins in someone's urine. This can result in what’s known as sick building syndrome. It typically occurs in people who, by their current health issues and genetic makeup, don't manage or eliminate mycotoxins very well.

Mycotoxins

We found three mycotoxins in my urine:

1. Very low levels of Ochratoxin A

2. Moderate levels of Citrinin

3. High levels of Mycophenolic acid

Mycophenolic acid is also a pharmaceutical drug called CellCept, an immunosuppressant used in transplant patients to prevent rejection. It is derived from a fungus and increases the risk of skin cancer. Does that ring a bell?

It's truly amazing when the puzzle pieces start to come together. When I returned for a follow-up visit, I brought the report to my dermatologist, and she was astonished we had uncovered that.

No, I haven't been taking CellCept. I’ve been exposed to at least one of the funguses that produces mycophenolic acid, not to mention the funguses that make citrinin and ochratoxin A.

I had my home checked for these molds, and the test came back negative. It makes sense because my house hasn't experienced water damage.

But I used to work in a building with extensive mold damage. Daniel believes I was exposed then, eventually colonizing my sinuses and gastrointestinal tract. Consuming these molds in food is also possible, but it is unlikely, given my strict diet.

Causes of Immune Compromise

Bringing things full circle, the article I referenced earlier about EBV reactivation lists multiple causes, three of which I’ve had:

• COVID-19

• Radiation (proton therapy)

• Mycophenolic acid

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My immune system is compromised due to multiple causes:

• Mycophenolic acid and the other mycotoxins

• EBV reactivation

• Proton therapy focused on my lymphatic system with collateral damage to my gastrointestinal system

• Small intestinal bacterial overgrowth

I'm not considering the possibility of long-term COVID-19 because my fatigue is improving as we tackle the EBV, SIBO, and bind and eliminate the mycotoxins.

The Fallout

I apologize that this was such a scientific article; I did my best to explain it in lay terminology. It's incredibly complicated and one of my most challenging experiences as we tackle each issue under the guidance of Dr. Kessler.

On top of physical and mental fatigue, I am currently experiencing medicine and supplement fatigue from taking so many medications and supplements.

I've also been experimenting with 12-hour fasts, during which I feel best when I don't have something digesting in my GI tract. But it's causing me to lose weight, which concerns me.

Intermittent fasting can be good for the immune system, but when your gastrointestinal system is damaged, it's a fine line to walk.

More importantly, we must tackle these issues to get my immune system back in shape to rein in this cancer. I have no other choice.

You can let setbacks take you down or incentivize you to succeed. I choose the latter.

Thanks for all your prayers and support.

Much love,

Keith