Although mast cells are best known for their role in mediating allergic diseases, recent studies have highlighted the important role that these cells play in the protection against infection with a variety of organisms. The Role of Mast Cells in the Defence against Pathogens. Urb & Sheppard. PLoS Pathog. 2012 Apr; 8(4): e1002619.
My Story II: The Aftermath
Getting rid of Blasto. and D.fragilis with two specialised drug treatments in 2001 allowed me to regain the 15 kilos I'd lost during the infection. The worst of the symptoms died down and some even vanished. The intolerable irritation in my colon, like a maddening burning itch, reduced in intensity and swollen lymph nodes in my neck shrunk back to their normal size.
In short I was now having more good days than bad. Compared to the horrendous symptoms I endured before the treatment, and having lived entirely without hope of recovery for the past 7 years, I was entirely grateful to have got this far.
Various treatments were tried and failed to allleviate the post treatment cycling symptoms, including Bismuth: a drug used to treat IBS; Rifaximin - an antibiotic used to treat small bowel overgrowth (SIBO) - twice and Sulfasalazine, a non-steroidal drug used to treat inflammatory bowel disease and which affects a spectrum of GI bacteria.
I resigned myself to living with post-infectious IBS symptoms indefnitely and gave up hope of anything helping me further along the path to better health. Then, one day about 7 years after Blasto. and D.fragilis were successfully treated, a drug used to to increase the appetite of patients with Inflammatory Bowel Disease cured the remaining symptoms and also cured my remaining food interolances.
The risk of PI-IBS appears to correlate with the severity of the infection.
The holiday of a lifetime
In 2007, I was about to go on yet another holiday dealing with symptoms which made me feel more like going to bed than away. Unusually, this particular flare up showed no signs of abating, so after a week I contacted the CDD (the clinic who treated my Blasto. and D.fragilis) for advice. They suggested Periactin, an anti-histamine used to improve the appetite of patients with Inflammatory Bowel Disease.
What happened on this drug was unlike anything I'd experienced since Flagyl completely cured my symptoms and food intolerances for 7 weeks back in 1994. A few hours after the first dose my bowel felt less inflamed and irritated. My mood felt lighter and I started to feel less unwell. After seven years of post-infectious symptoms it was nothing short of a miracle. I left for my holiday chronically tired - a temporary side effect of Periactin - but feeling better than I had for many years.
The infection had also left me with significant food intolerances, including a sensitivity to sugars. Feeling encouraged, I cautiously expanded my diet to include summer fruits and delicious apple pie - all foods which normally trigger the forewarning symptoms of a bad flare up: under eye oedema, sneezing, an increasingly sore bowel, feeling unwell and chronic tiredness.
Incredibly, my insides stayed calm and no 'allergy' type symptoms appeared.
After my fabulous holiday feeling almost "normal" healthwise I emailed the CDD to tell them what happened, as well as to discover why a drug used to improve appetite had such a have such an unexpected effect on my symptoms. Their reply was disappointing. They had no idea why some of their other patients had such a profound reaction to the drug, as I had.
Three months later the drug stopped working, even after a doubling the dose. When other over-the-counter anti-histamines had no effect I had no choice but to try and unravel the mystery of why a specific anti-histamine made my symptoms all but disappear. If I could figure this out, perhaps I could discover other drugs which give the same relief.
A new treatment
One day on my search for a connection between parasites and disorders of the immune system I came across the medical disorder Systemic Mastocytosis - a mast cell disorder whose symptoms considerably overlap with Blasto. and D.fragils. More about mast cells and parasitic infections here.
Someone from the Sydney based Masto. Society gave me the name of a haematologist who deals in mast cell disorders. Apparently most don't. She also told me about two drugs used to treat SM symptoms: Ranitidine (Zantac) a histamine H2-receptor antagonist and cetirizine (Zyrtec) an H1-receptor antagonist. Within 3 days of starting these drugs my symptoms died down. I ate normally and I started to gain more weight. Was this the 'cure' I'd dared hope for.
Just short of three months the effects petered out. Doubling the dosage had no effect. It appears I had built a tolerance to the drug.
My consultation with the hematologist coincided with being symptom free because I was still on the mast cell inhibitor (Cromyln). Nevertheless the haematologist thought that my symptoms off the drugs and two blood markers (which became apparent a couple of years after I first fell ill back in 1996) fitted the medical profile of SM, so the next day I underwent a bone marrow test. The result was negative. I didn't have SM, which was a relief. But the doctor just wasn't interested in my theory that the seven year chronic parasitic infection could have triggered an immune disorder involving mast cells - one which was not diagnosable by a bone marrow test. Nevertheless I took the specialist at his word when he suggested I rebook if my symptoms come back. Eventually I built a tolerance to Cromlyn so I returned for my second appointment:
Specialist: "Why are you here? Your result was negative".
Me: "You told me to come back if my symptoms returned.".
Specialist: "You don't have a mast cell disorder. I suggest you see an allergist".
I read his referral to the allergist. After years of having a chronic GI infection misdiagnosed as IBS I'm well versed in the hierarchical nature of medicine and how it can affect the outcome of an appointment. For instance, if a top specialist in his field diagnosis IBS when you have parasites the next specialist is unlikely to go against the grain. Therefore I was dismayed to read the only reference to my seven year battle with D.fragilis and Blasto. contained in his referral letter was "There was some talk of a parasite...".
The doctor at the allergy clinic took copious notes about my seven year infection and my current state of health before excusing himself to discuss my case with the registrar. Five minutes later he returned with the registrar, who asked me to repeat my story. My suspicions, based on the content of the hematologist's referral letter, that the appointment was not going to turn out well was horribly confirmed when the registrar allergist declared adamantly that "D.fragilis and B.hominis do not cause symptoms and anyway, if you'd had a parasite you would have been very sick." and "The one thing you do not have is a mast cell disorder.".
Mast cells are more well known for their harmful effects during inflammatory conditions such as asthma and allergy. However, the role of mast cells in GI infections has largely been ignored which is interesting because this reaction seems to have evolved as a defense system against intestinal worm infestations (Mixed Organic Brain Syndrome as a Manifestation of Systemic Mastocytosis. Psychosomatic Medicine Vol. 48, No. 6 (July/August 1986).
The main and only reason for the consultation was to obtain sodium cromlygate - another mast cell inhibitor. Naturally my plan didn't work out, but in the end I was able to import the drug from the US with the help of a sympathetic GI specialist. For a little over $AUD600 (it had to be ordered in bulk) the symptoms once again disappeared. The positive effect petered out after about three months. I was distraught to read the fine print on the manufacturer's website which stated that some patients build a tolerance to sodium cromlygate. (Details of other treatments for unruly mast cells below).
A few months later I ventured out again to seek the opinion of doctors at another major Sydney teaching hospital. They prescribed the same drugs used to treat mast cells I had taken when I first discovered the relation between gut infections with Blasto. and mast cells Zyrtec and Zantac. Obviously that visit wasn't much help because I had built a tolerance to these drugs.
What totally cured my remaining symptoms was the anti-psychotic drug Ziprasidone (see below), which doctors sometimes prescribe "off-label" to treat intractable depression. This drug suppresses pro-inflammatory cytokines and increases pro-inflammatory cytokines. I fell into a severe depression after the death of the person who got me through the illness. Without him I probably wouldn't have made it. The drug completely cured my remaining symptoms, which to me proved my theory that the immune system can become oversensitised in people who suffer long term severe symptoms. This problem is not yet medically recognised. (2013)
Post script 2015: A major Sydney teaching hospital is now prescribing this drug to patients who only partially respond after eradication of their gut infection, like me.
Mast cells and/or basophils have been implicated in the expression of a wide variety of biological responses, including immediate hypersensitivity reactions, host responses to parasites and neoplasms, angiogenesis, tissue remodeling, and immunologically non-specific inflammatory and fibrotic conditions. Recent findings suggest that an important mechanism by which mast cells influence such biological responses is through the production of a broad panel of multifunctional cytokines. Cytokine production by mast cells and basophils. Stephen J. Galli, John R. Gordon, Barry K. Wershil. Volume 3, Issue 6, December 1991, Pages 865-873
Sodium cromylgate has been used to treat food allergies (Byars & Ferrares 1976)
Other treatments for Mast Cell Disorders:
Ketotefin (similar to Periactin): A study shows that ketotifen reduces discomfort in patients with IBS, reduces IBS symptoms overall and improves health-related quality of life. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut 2010;59:1213-1221
Benzodiazapenes: These drugs inhibit mast cells but their potential for addiction and misuse means that doctors are often reluctant to prescribe them. This is unfortunate for patients who could be helped by this drug during major symptom flare ups. Panic Disorder, Interstitial Cystitis, and Mast Cells. Theoharis C. Theoharides, PhD, MD, MS. J Clin Psychopharmacol. 2004 Aug;24(4):361-4.).
Marijuana: In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. Cannabis Finds Its Way into Treatment of Crohn's Disease. Pharmacology. 2013 Schicho R Storr M. Cannabis has powerful anti-inflammatory properties which can soothe inflamed bowels. According to an article in New Scientist August 2005, experimental evidence suggests that cannabis may protect against colonic inflammation, leading to the possibility that activation of this system may have a therapeutic role in inflammatory bowel disease (IBD). Cannabis use amongst patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2011 Oct;23(10):891-6. Lal S et al.
Further reading: Cannabinoids for the treatment of inflammation.
While we're on the subject marijuana is also being recognised as a treatment for epilepsy. Researchers working at Brtains University of Reading found that mice afflicted with six types of epilepsy and found it "strongly suppressed seizures" without causing shaking and other side effects of existing anti-epilepsy drugs. The findings were reported in the British Journal of Pharmacology. (Epilepsy breakthrough. SMH. Sept 16, 2012.)
Apart from its intended use, antipsychotic medications, clozapine, olanzapine, risperidone, are sometimes prescribed off-label to treat severe depression short term. These drugs also affect the immune system in a positive way in that they suppress immune cells responsible for inflammation and increase the release of anti-inflammatory immune cells. Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 17 March 2009. Haruhiko Sugino et al
Various triggers can activate mast cells:
Bacteria are powerful antigens for the gastrointestinal immune system Need for a comprehensive medical approach to the neuro-immuno-gastroenterology of irritable bowel syndrome. WJG. 2011. Karteraei et al. Perhaps that's why so many report an increase in their Blasto. symptoms on probiotics. Don't just take my word for it. The problem is highlighted in a study by the London School of Tropical Medicine and Hygiene where trials indicated that different probiotics can improve, have no effect, or even worsen symptoms. Probiotics and prebiotics in the management of irritable bowel syndrome: a review of recent clinical trials and systematic reviews. Curr Opin Clin Nutr Metab Care. 2011 Nov;14(6):581-7. Whelan K.
Stress can also trigger mast cells.
Individuals with who end up with a mast cell disorder after years of Blasto. symptoms may aquire other triggers related to this disorder including, but not limited to, intolerance to exercise, red wine, heat (ie sitting in hot sun). These symptoms also appear in other patients with unruly mast cells - Systemic Mastocytosis.
Unusual Blasto./D.fragilis symptoms and mast cells:
Parasites can cause all manner of odd symptoms. Rectal itching (pruritis) is fairly common in people with D.fragilis and B.hominis. Intense colonic irritation is less common but nevertheless can cause great distress to the sufferer.
Proliferation of mast cells in the skin and release of histamine are established as a cause of itching in other illnesses. Histamine provokes intense itching by acting directly on the free nerve ending or indirectly through mast cells.
Is this intense burning irritation experienced by some triggered by histamine released from mast cells in the GI tract? If so then perhaps this is the ultimate unscratchable itch because it's internal!
The sensations of itch and pain have a lot in common, and recent data suggest that there is a broad overlap between pain and itch-related peripheral mediators and receptors. Acta Derm Venereol 2008; 88: 121–127
A few examples:
A Sydney man infected with B.hominis and D.fragilis whose symptoms included abdo pain, bloating, burping, moderate to extreme pain in the colon region, chronic constipation, diziness and weight loss wrote: "Your description of hot glue being stuck in the colon is spot on.".
A woman from the US also with Blasto. wrote: "I have this very strong burning pain in the area of my left hip bone."
A Sydney-based lawyer was, eventually, successfully treated for Blasto after years of illness: "I had a pain in my lower abdomen on the left and sometimes immediately below the belly button. It was a burning pain that seemed to get worse almost as soon as I had eaten some food, sometimes it would be so bad I would get chills. I went back to my GP and pleaded for him to help me. He said he thought I had post natal depression ( my daughter was 2yo!) and that the pain would probably go away in time, he prescribed antidrepressants, which I never took."
A man from the Ukraine diagnosed with B.hominis after 15 long years of symptoms described a "chronic burning pain" around his anal area and inside his rectum.
A young Australian woman was so distressed by the intense irritation in her colon that she often felt like "cutting out" her bowel. The GI specialist she consulted was adamant that she could not possibly be experiencing such a symptom. Linda (not her real name) suffered many other GI and systemic symptoms, but stool and other medical tests had failed to reveal a cause.
Panic attacks and Blasto. symptoms
Some people experience panic attacks which starts around the same time as other Blasto. symptoms.
For instance, J. from Sydney, wrote that his panic attacks started shortly after the onset of other symptoms including: "Nausea, dizziness, occasional diarrhea, lots of gas (lots of burps), stomach gurgling, loss of appetite and frequent urination".
J. struggled to keep his job because he felt so unwell. One day he felt so sick and dizzy he almost passed out: "Blood rushed to my head, the room started spinning, I felt extremely dizzy. I excused myself and tried to use the bathroom because the nausea overwhelmed me. I sat at my desk for about an hour, convinced the dizziness was gone and I could drive home, then did go home and slept for about 3 hours".
J. allowed me to publish his symptom diary, which he kept for 3 weeks prior to taking the triple therapy, after which his symptoms and panic attacks subsided.
Diary: Friday, June 21: I woke up nauseous. It was a 'fun-day' (day off from work that you spend w/ your co-workers). I didn't want to miss it so I stuck it out. We played laser-tag and then went rafting. I felt extremely sick on the raft but where could I go? I stuck it out.
Saturday, June 22: I woke up nauseous but got in the car to take my daughter to summer camp anyway. We got 30 minutes into a 5-hour trip and I had to get my wife to drive me back home. I was burping continuously in the car. I slept for most of that day.
Sunday, June 23: I felt a little better when I woke up. I took it easy all day.
Monday, June 24-Friday, June 28: I was okay. I felt fine.
Saturday, June 29: I woke up nauseous - lots of burping again. I was supposed to play golf w/ a friend but had to cancel. I slept all day except for about 3 hours. Sunday,
June 30: I was a little nauseous but feeling a little better. I still had lots of burping. Monday, July 1 and Tuesday, July 2: I was perfectly normal/fine.
Wednesday, July 3: I woke up nauseous - lots of burping. As soon as I got to work I knew I wouldn't make it so went home. That day I saw our family physician who took blood and urine and gave me a stool sample kit. We had to cancel a trip to visit relatives for the holiday.
Thursday, July 4: I felt nauseous all morning - lots of burping. I started feeling better by the late afternoon.
Friday, July 5: I still felt a little nauseous but not too bad. I delivered the stool sample to the doctor’s office. I started feeling better as the day went by. I drove 5 hours to Galax, VA, to stay w/ relatives so we could pick up my daughter from summer camp the next morning.
Saturday, July 6: I drove 5 hours home from the summer camp. I felt perfectly normal/fine.
Sunday, July 7-Monday, July 8: I felt perfectly normal/fine.
Tuesday, July 9: I felt perfectly normal/fine. Dr.xx called with news that I had Blastocystic hominis and called in a prescription. I started the Flagyl at lunch-time that day.
Wednesday, July 10: I felt perfectly normal/fine. I took half a day to play golf. I was exhausted after the round but that's normal for me. I probably made a mistake but I had a huge plate of spaghetti for dinner that night.
Thursday, July 11: I felt perfectly normal/fine. I traded emails from the “contact” on BadBugs web site I’d found on Tuesday. I was in a training session that morning for about an hour and I had this dizzy spell. I came home and slept for several hours.
Friday, July 12: I felt perfectly normal/fine. I took my daughter to softball practice that evening and felt okay to go play poker w/ the guys till midnight.
Saturday, July 13: I woke up in a major panic. This was new. I was having some sort of panic attack or nervous breakdown or something. I took one of the nausea pills. I was a bunch of nerves, disoriented, loss of control. There were several moments when blood rushed to my head, and I felt like; “oh, no!” and I didn’t know what was going on. I couldn’t catch my breath, had major nausea, and was extremely upset. (My wife) took me to the ER about 10:30am. I was in la-la land - head spinning, very emotional. I thought I might be having a heart attack or something. As I waited for the doctor I tried but could not remember what medicine I took that morning. (My wife) told me I’d told her I taken the nausea medicine but not the Flagyl. Eventually I did remember. That was weird.
(During the attack) I had anxiety, panic, overwhelmed w/ fear but of nothing in particular, couldn’t catch my breath, chest tight, stomach in knots, out of control, disoriented, scared, depressed, thoughts of suicide. After about half an hour I started feeling better. (The hospital dr) took blood and urine and did a chest X-ray. Results came back normal. They sent me home saying it was probably just stress and that I should see my GP on Monday. I got home around 2:30pm and slept for about 3 hours. A little while after the anxiety started again. It was just like before. I had all sorts of strange conversations going on in my head. I went to bed at 8pm but couldn't sleep for hours. I was a nervous wreck. I had all the symptoms above again.
Sunday, July 14: I woke up at 3am in a panic - suicidal. I paced around downstairs and I grabbed a blanket and wrapped up as tight as I could. Somehow I drifted off to sleep in a chair in the TV room. About 7:30am I woke up and wrote this document.
Gary, another Blasto. sufferer, also cited panic attacks which coincided with other symptoms:
"I have frequent, diarrhea-like bowel movements, foul smelling stool and gas, mainly loose stool particularly exacerbated by beer, wine, pizza etc. Most food makes me feel ill. Constant heavily coated tongue which I brush off daily but it comes straight back. Tastes gross. Burping constantly. Shocking stomach pain just under my left rib, bowel pain mid to lower left hand side and heart palpitations. Passing undigested food, long stringy things in the toilet bowl. I also have bouts of anxiety, severe mental fog and lowered resistance to stress, dizziness/feeling of vertigo, rapid heartbeat, heat spreading through upper back and chest, dry throat, internal quivering and abdominal distress.".
Unfortunately Gary was refused a chance to find out if, or by how much Blasto. was responsible for his poor health because his doctor does not believe B.hominis causes symptoms. Instead Gary was diagnosed with stress-related IBS. (2010).
More about mast cells here.