Week 9 Review

Today I inoculated with a second dose of hookworms (40).  The experience has been much like the first time - pin pricks going in and a faint rash at the beginning.  I now have a total of 70 hookworms and 300 whipworms.

I have discontinued prednisone and will continue taking entocort and asacol for the foreseeable future.  I had one instance of red streaks in my stool this week but otherwise I have been fine.

Week 8 Review

While my doctor suggested discontinuing prednisone on Monday I decided to do one more week at 2.5mg/day just as insurance against withdrawal symptoms.  At week 7 I would say my hookworm rash had completely disappeared.  I have generally been doing well.

Week 6 Review

On Monday I decreased prednisone to 5mg/day.  In two weeks I will only be on entocort.  I'm feeling considerably less wired (an effect of the prednisone) and my appetite has not been as insatiable.

And this morning I took my second dose of whipworm - 200 ova.  Five more doses (spaced 6 weeks apart) remain.

Week 5 Review

The rash has continued to fade and not much else has changed.  I also saw my GI on Tuesday. He wants me to continue to taper off prednisone and try to establish a "maintenance" dose of entocort.  I should note that I am not tapering off prednisone in hopes that the helminthic treatment is working.  It will be many more months before the whipworms are fully colonized and John Scott sent me this really great post by Jasper Lawrence on why Chron's sufferers should really wait close to a year before attempting a med taper in favor of helminths.

Rather, I am tapering off of prednisone in favor of entocort (a formulation of budesonide) at my doctor's recommendation because it has fewer systemic side effects.  Prednisone is quite simply nasty stuff to be on long term.  My first blog post coincidentally was during the first week where I had started taking budesonide and had begun a slow tapering down from prednisone at 40mg.  I began the prednisone after my extremely bad 6MP reaction.

"Normally" I haven't taken either prednisone or budesonide as maintenance medications.  I have been taking Asacol for roughly 12 years and for most of that time it seemed like it has supported remission but the last couple of years have been rocky and I have had to use prednisone several months at a time to quiet some bad flares.  It's my doctor's opinion that I may need to be on something like budesonide long term.  Of course it's my hope that it won't come to that.

As an aside, even if the helminthic therapy produces good results I don't plan on eliminating Asacol from my regime.  I seem to tolerate it fine; it has few side effects; and there's even some evidence that it may be protective in colo-rectal cancer [Tang 2010].

Week 4 Review

On Monday I reduced prednisone to 10mg/day.  The hookworm rash became very angry this week (continuing from last week) but has since started to subside.

Week 3 Review

For 4-5 days early in the week I had really bad gas.  It didn't manifest in pain or bloating but the smell was truly toxic and prolific.  My wife wondered if it might be my GI microbiome re-aligning with the helminths.  That sounds a bit feng shui to me but I think the gas is likely helminth related because otherwise my diet hasn't changed.  These symptoms are listed in the hookworm timeline as an uncommon but observed side effect that may happen in week 3.  Fortunately the gas passed a few days ago.

I was also surprised that the spots that make up my rash have become raised and more pronounced this week.  The hookworm timeline suggests this may be a consequence of the hookworms becoming adults and attaching to the intestinal wall and the immune system is reacting in kind to both the worms and the debris left in the skin.

Week 2 Review

I had more bloodwork done yesterday and everything is in range except for my platelet count, which is still low from my 6MP encounter.  But the good news is that it is slowly climbing.

On Monday I reduced my prednisone to 15 mg/day per doctor's instructions and will continue to taper down 5mg every two weeks.

I've felt pretty good for the last couple of days.  While the hookworm timeline says this about the right time for a "worm bounce" (a sudden improvement in symptoms) I actually attribute feeling a bit better to the lower prednisone dose.  Prednisone makes me feel really wired and each time I have lowered my prednisone dose, I've felt a little calmer.

Week 1 Review

Today ends the first week of helminthic treatment.  The rash on my arm is less red overall although the individual hookworm entry points are now much more distinct.  I really had only one day of slight itching and no other significant changes.

Day 3

Or, "What to Expect When You're Expecting.. Worms"

Jasper Lawrence and John Scott have put together an excellent hookworm timeline.  In the next few days the hookworms should be migrating via the lungs to the small intestine where they will mature.  At the same time the whipworm eggs should be hatching in the small intestine and after a week they should migrate to the large intestine.  It will be weeks before the worms are mature and probably months before I really know if they are helping to maintain Crohn's remission.

Day 2

I have had only a very slight periodic itch at the inoculation site.  The rash itself is already starting to fade and look more diffuse but at one point in the day the little marks looked particularly crisp and I counted roughly 20 of them but at the center they were so clustered it's easy to believe all 35 may have made it in.  I have circled the rash site in the photo below.

Day 1

Today is inoculation day.  I am beginning with 100 TTO and 35 NA.  As mentioned in my previous post, I am taking prednisone so my reaction to both the TTO and NA is likely to be duller (less itching or other effects) than had I not been on prednisone.  AIT actually recommends taking prednisone to patients who have or think they might have a stronger reaction to infection.

The TTO comes in a small vile to be ingested.  I was a little surprised that when I was going to swallow it nothing came out.  The surface tension of the fluid was actually holding it in place because the vial is so small.  Tilting the vial more slowly instead of trying to take it like a shot of whiskey did the trick.  I then rinsed the vial with tap water drinking the rinse water each time.  The solution is slightly salty but there's hardly enough of it to really even taste it.

The NA kit comes with two small vials.  The first contains the hookworm and the second contains a rinse solution to dislodge hookworm that may be hanging on to the sides of the vial.

One applies the hookworm on a bandage and then uses the rinse solution on the hookworm vial.  The rinse solution is then also added to the bandage.  The bandage has adhesive on all four edges to keep the solution in but really the cotton part of the bandage does that well enough - it's not a lot of fluid so the bandage feels only ever so slightly damp.  I added a little bit of loosely wrapped co-flex just as insurance that the bandage would not come off.

Within five minutes I felt the first pin prick and then shortly after a cascade of other little pricks.  After ten minutes the excitement was over.  I will continue to wear the patch for at least four hours in case there are any stragglers.  I haven't noticed any itching or other ill effects.

I began this procedure at approximately 3am while the rest of my family was asleep.  Because of the prednisone this is when I wake up "normally".  While supportive, my wife didn't actually want to see me doing this so it's the perfect time.  I have to admit a slight urge at 4am to shout, "Argh.. The worms have got me!"

Baseline

Due to my recent bad reaction to 6MP I wanted to make sure I had a good baseline to start from before treatment with NA and TTO.  I had blood work done this morning and both my doctor and myself were surprised to find that one of my levels, the platelet count, had not completely rebounded.  Normal platelet counts should be between 130-450 billion/L but mine is at 115.  While this is low it's certainly not critical and with hookworms sitting on the shelf I've decided to go ahead and begin inoculation tomorrow.

My CBC showed red blood count, hemoglobin, hematocrit, and white blood count are all in normal ranges.  Furthermore segmented neutrophils, lymphocytes, monocytes, eosinophils, basophils, and absolute neutrophil are all in normal ranges.  Platelet count (115) differs from norm by roughly 15 billion/L.  Iron and B12 were also in normal range.

My weight is 84 kg (increased weight due to effects of prednisone) with height at 1.8 meters.

My current drug and supplement regime includes:

• Asacol (3200mg/day)
• Prednisone (20mg/day)
• Entocort (9mg/day)
• Flintstones Complete Multivitamin (1 a day)
• Ultimate Flora Adult 15 (1 a day)
• Vitamin D Supplement (2000 IU/day)

The Flinstones vitamin is chewable and contains iron (not all multivitamins do).  I will over the next weeks be tapering both the prednisone and entocort and in fact have already tapered the prednisone down from 40mg/day in mid-April.

The Hygiene Hypothesis

The hygiene hypothesis asserts that a lack of exposure to infectious agents, symbiotic microorganisms, and parasites increases susceptibility to allergic and autoimmune diseases.  The hypothesis gives one explanation of the increase in allergic and autoimmune diseases since industrialization and the higher incidence of allergic diseases in developed countries.

Dr. Joel Weinstock is one advocate of this theoretical framework in explaining the increasing incidence of Crohn's disease.  Late last year Nature published a piece by Weinstock titled Autoimmunity: The worm returns.  If you haven't heard of the hygiene hypothesis or its relevance to Crohn's disease, I can't recommend this article enough as an introductory text.  When I went to talk to my GP and my GI about doing this, I gave them each a copy of this article.  Fortunately both of my doctors have been very supportive and although neither can recommend this my GI has said he will be very interested to see what happens.  Intellectual curiosity; I like that.

One other piece on the hygiene hypothesis that I wanted to highlight is the obscurely titled and obscurely linked Coronado Bioscience Analyst Meeting.   This is a webcast of a power point presentation given by scientists associated with Coronado Biosciences and it has an extremely good explanation of the history of the hygiene hypothesis and a description of where the research on helminthic therapy is now with the actual doctors and scientists doing the research.  (Note that you have to register to watch the webcast but it's only a matter of entering an email address.)

The Worms

The research on helminthic therapy and Crohn's has primarily considered three different species:

1. Human hookworm (Necator americanus or NA)
2. Human whipworm (Trichuris trichiura; Trichuris trichiura ova is abbreviated TTO)
3. Pig whipworm (Trichuris suis; Trichuris suis ova is abbreviated TSO)

Helminthic therapy involves infecting oneself with the larvae of these worms in the case of hookworm and the ova of these worms in the case of whipworm.

Most of the current studies consider TSO because unlike human hookworm and whipworm, the human body isn't the natural home for Trichuris suis and it dies off after only a few weeks and presents no opportunity for reinfection.  This also means one must continuously reinfect oneself with the ova, which if you are a pharmaceutical company is attractive because you can treat TSO similar to any other medication.  A company called Coronado Biosciences in currently engaged in a number of Phase 1 and Phase 2 trials of TSO for Crohn's and other diseases.  TSO is available from a German company called Ovamed and at the doses being tried in studies is quite expensive at over $16,000 a year.

Trichuris trichuria by contrast can live in the body for roughly 18 months and Necator americanus can live in the body for 3 to 5 years.  While these worms can in theory spread to others, modern sanitary practices (i.e. toliets) make this virtually impossible as both worms must live in infected soil under specific conditions and then be reingested (see also CDC's whipworm lifecycle) or exposed to bare skin (see also CDC's hookworm lifecycle).  While there are fewer studies currently considering TTO and NA, the evidence suggests the genetic makeup of TTO is very similar to TSO.  TTO and NA are available from UK-based Autoimmune Therapies (AIT) and Mexico-based Worm Therapy (WT).  See also List of Helminthic Providers.  For both reasons of cost and convenience I have decided to try a combination therapy of TTO and NA from AIT.

The Subject

This blog follows my own battle with Crohn's disease (CD) for which I was diagnosed in 2001 (I'm presently in my mid 30s).  Crohn's disease is a type of inflammatory bowel disease (IBD) characterized by an immune system response that attacks the body's gastrointestinal tract.

My symptoms present as abdominal pain, rectal pain, diarrhea, fecal incontinence and malabsorption.  And that's on a good day. On particularly bad flares I also have frank blood and mucus stools, fatigue and flu like symptoms including fever and chills.

Findings from colonoscopies and upper GI endoscopy have found: 
Inflamation in the sigmoid colon (no ulceration); abnormal upper GI consistent with Crohn’s disease involving ileum and duodenum

; 
inflamation from the rectum secondary to Crohn’s disease.

For me prednisone has historically worked well to induce remission (or at least suppress symptoms) but maintaining remission has always been challenging.  My diet seems to have very little effect on remission - I have tried a vegetarian diet, a milk-free diet, and a gluten-free diet but none offer any relief.  I have no known food allergies.  The only thing that I have observed in my own diet is that during a flare low fiber foods are less painful to digest than high fiber foods. I've found the best solution is simply not eating: no food; no pain.  CD literature suggests there's something to this - one effective CD treatments is enteral nutrition or an elemental diet, which essentially bypasses some of the digestion process [Grover 2013, Zachos 2007, Day 2006].

With respect to maintenance drugs I have had the best success with asacol (mesalamine) but in recent years my symptoms have become more persistant and flares more common even with asacol.  I have also tried other formulations of mesalamine, antibiotics, and very recently 6MP (mercaptopurine).  None of these drugs has a great track record for maintaining remission; often no better than placebo [Change 2013, Chambrun 2012, Bjerrum 2011].  Despite having taken a genetic marker test and getting frequent blood tests 6MP put me in the hospital after almost eliminating my white blood cells and platelets.

The next options for me include biologic immunosuppressants such as humira and remicade but these have serious risks and side effects and relatively poor efficacy in maintaining remission.  And while steroids have worked extremely well for inducing remission they don't support maintenance well and have serious long term side effects.

One promising treatment that I will be exploring in this blog is using helminths to down regulate the immune system response.  This is part of a body of thinking called "The Hygene Hypothesis."  The hypothesis suggests that in sanitizing our environment and reducing exposure to bacteria, microbes, and parasites we, as a society, are upsetting a natural symbiotic balance.  Some studies have suggested that hookworm and whipworm exposure may support remission maintenance better than existing solutions [Kabeerdos 2011, Croese 2006, Reddy 2008, Weinstock 2005, Summers 2003].  But this is still science in progress and studies on this approach have been promising but small.  Unfortunately I don't feel that I have time for the science to be settled and in this blog I'll examine how well it works on me.

Words of warning: I am an academic but I am not a medical doctor and nothing on this blog should be considered medical advice.