Reprinted with the kind permission of Cort Johnson and Health Rising
“The dramatic response to therapy in this patient is remarkable and could help others who suffer from POTS and MCAS.” The authors
This, the fourth and last of a series of blogs featuring IVIG, and in this case other treatments, was sparked by attending the 2018 Dysautonomia Conference in Nashville, Tenn. It focuses on a case report of a severely ill POTS patient who improved dramatically using a combination of novel treatments – at least novel for most doctors. Whether you have POTS or not, this report is worth reading as it demonstrates the impact a knowledgeable and creative doctor who is willing to entertain non-traditional diagnoses and treatment methods can have on people with complex illnesses such as ME/CFS/FM and POTS.
If a doctor wants to spread news of a better treatment approach, there are several things they can do. They can tell their colleagues or speak about it at a conference. Short of participating in a study, though, the best way to spark interest in it is to write up a case report and get it published.
That’s what happened here but this wasn’t your normal case report. Emblazoned across the top of every page of the case report,
were the words:
“Novel treatment (new drug/intervention; established drug/procedure in new situation)”
The authors didn’t only illuminate a novel treatment regimen: they applied it to two conditions that many doctors either don’t know about (POTS) or may not believe exists (mast cell activation syndrome (MCAS)).
Brent Goodman at the Mayo Clinic in Phoenix was the MD associated with this case. He’s been on a tear trying to educate other doctors about POTS and MCAS, and the education began early in the case report.
IBS or MCAS or POTS?
First, the authors noted that about 30% of POTS patients appear to have MCAS – a disease with similar symptoms. Then, they asserted that the gastrointestinal symptoms most doctors associate with irritable bowel syndrome (IBS) are instead being produced by mast cells in the gut or autoimmune antibodies that are messing with the autonomic nervous system, which impacts the gut. It turns out that the gut symptoms caused by mast cell activation (abdominal pain, bloating and abnormal bowel function) are identical to those found in IBS.
The authors also took exception to how most doctors treat POTS. Not enough focus, they asserted, is being paid to non-orthostatic (standing) issues such as the gut. Since POTS affects the autonomic nervous system, it makes sense that it would affect the gut as well, but that aspect of POTS has been mostly ignored.
A Tough Case
They took the hardest of cases – the ones doctors hate to see – to highlight their treatment approach. This woman, now 43 years of age, had desperately tried to get well, seeing 19 physicians in 16 years.
She had been a working professional (a biostatistician) and self-described high achiever. Her path through the medical profession – which included multiple diagnoses but not much help – will be recognizable to many. So will the individual bootstrapping and research she did which ultimately led her to better health.
Her flushing, edema and other symptoms dropped dramatically after IVIG.
She first experienced signs of MCAS (flushing, itching, wheezing, and dizziness and nausea in response to certain foods) when she was 18. Doctors diagnosed her with rosacea and restless leg syndrome (RLS), and she received antibiotics, laser treatment, iron supplements and drugs like Ropinirole (which didn’t work). Her facial flushing improved but her other symptoms continued to worsen. By the time she turned 20 she was having gut problems (bloating/pain, constipation and foul-smelling stools) as well.
In her mid-twenties, she developed orthostatic intolerance, body pain, and weakness and edema in her legs, resulting in disability. Eventually her gut issues got bad enough to have her go on a liquid diet. Her dizziness led a cardiologist to refer her to a neurologist, who, thinking she had Lambert Eaton Myasthenic Syndrome (she did not), referred her to Mayo. In 2006, Mayo diagnosed her with “excessive venous compliance” but, remarkably, all they could recommend were compression stockings and a pysch evaluation! (No blood volume enhancers, no drugs – of the numerous ones available – no dietary recommendations, and they apparently didn’t give her a tilt table test…She declined the psych evaluation.)
Her health continued to plummet. Her thyroid (Hashimoto’s thyroiditis – an autoimmune disease) was the next to go, and then in 2010, three Doppler ultrasounds indicated she had chronic venous insufficiency. Instead of the blood flowing back up to her heart, the blood, when she stood up, flowed back down to her feet. She was having trouble sitting up, let alone standing.
Seeing a gastroenterologist for her gut issues in 2012 proved worthless, but in 2013 she made a discovery that changed her life. After receiving a boost from Claritin, an antihistamine, she diagnosed herself with mast cell activation syndrome (MCAS) and POTS (!). Then she referred herself to the Mayo Clinic in Phoenix, (apparently to Dr. Goodman, the expert in those diseases there), and her self-diagnosis was confirmed.
Dr. Jill Carnahan reports that the following over-the-counter drugs or supplements can block MCAS symptoms. If you experience MCAS symptoms and these make you feel better, it stands to reason that you may have MCAS. (Not responding to these treatments, on the other hand, does not mean that you don’t have MCAS.)
- Diphenhydramine (Allergy Relief, Allermax, Banophen, Benadryl, Compoz Nighttime Sleep Aid, Nytol QuickCaps, PediaCare Children’s Allergy, Q-Dryl, QlearQuil Night time Allergy Relief, Simply Sleep, Sleepinal, Sominex, Tranquil, Twilite, Unisom Sleepgels Maximum Strength, Valu-Dryl, Vanamine PD, Z-Sleep, ZzzQuil and many others)
- Loratidine (Claritin, Claritin Liqui-Gels)
- Cetirizine (Zyrtec, All Day Allergy)
- Famotidine (Pepcid, Pepcid AC); Cimetidine (Tagamet, Tagamet HB); Ranitidine (Zantac)
Mast Cell Stabilizers
- Cromolyn, Ketotifen, Hyroxyurea
Natural anti-histamines and mast-cell stabilizers
- Ascorbic Acid, quercetin, Vitamin B6 (pyridoxal-5-phosphate), Omega-3 fatty acids (fish oil, krill oil), Alpha Lipoic Acid, N-acetylcysteine (NAC), Methylation donors (SAMe, B12, methyl-folate, riboflavin)
It was not apparently until she met up with Dr. Brent Goodman in 2103 in the Phoenix Mayo CLinic that someone thought to measure her heart rate while standing. A doubling of her heart rate (from 80-160 bpm) within 10 minutes of standing suggested POTS. She also experienced a facial rash, edema, blue hands and Terry’s fingernails and dermatographism (hives).
Terry’s nails appear white with a ground glass appearance and are missing the lunula – the white crescent shape usually seen on the bottom of the nail. Most of the nail appears white except for a narrow pink band at the tip.
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The color changes are believed to result from a decrease in vascularity and an increase in connective tissue in the nail. This commonly occurs in diabetes mellitus, hyperthyroidism, malnutrition, liver failure, and other systemic diseases. Terry’s nails may also reflect aging.
A tilt table test and blood samples confirmed a diagnosis of hyperadrenergic POTS (increase in heart rate >30 beats/min, rise in systolic blood pressure ≥10 mm Hg and serum norepinephrine level ≥600 pg/mL). Further testing revealed impaired sympathetic nervous system functioning in her feet plus low leukocytes, platelets, thyroid (T3 and T4) and elevated 24-hour urine leukotriene, creatinine and prostaglandin levels.
Interestingly, her 24-hour N-methylhistamine levels were normal. None of the other mast cell tests were mentioned. (Jill Carnahan mentions 7 possible MCAS tests)
Her only sign of autoimmunity was a positive antithyroid peroxidase antibody. None of the 19 other antibodies tested for, including Sjogren’s and lupus, were positive. Goodman gave her an MCAS diagnosis on the basis of her having 47 of 48 known MCAS symptoms as well as meeting other MCAS criteria.
Check out the criteria for MCAS diagnosis here
She was also diagnosed with ”delayed pressure urticaria /angioedema” (DPU), which occurs when pressure applied to the skin is followed by swelling and pain. She was in a tough spot: her POTS left her unable to walk while her DPU left her unable to lie down without pain. The DPU diagnosis did have a silver lining, though; it was what convinced the insurance company to give her IVIG, which did her a world of good.
Thyroid replacement stopped her restless leg syndrome (RLS) in its tracks, but a basketful of POTS treatments (midodrine, amphetamine, droxidopa, support stockings, high salt diet) and MCAS medications (cromolyn sodium, monteleukast, antihistamines (hydroxyzine and all over-the-counter H1 and H2 blockers) failed to provide benefits.
Ultra-low dose naltrexone (1 mg every night), however, improved her pain, mood, memory, sleep, flushing, food and odor sensitivities and tingling in her limbs.
IVIG 1.5 g/kg (Privigen) and 125 mg methylprednisolone given once a month had a tremendous effect. Within a week of her first infusion, her fainting, tinnitus, anal outlet disorder and vascular spasms stopped. Her now normal capillary refill time (>1 min before IVIG; <2 seconds after it) indicated her cardiovascular system was responding. (Capillary refill time is the time it takes for the color of the soft pad of a finger or fingernail to return to normal after pressing on it until it appears white.)
Next, a lactulose breath test indicated she was exhaling hydrogen gas and therefore had small intestine bacterial overgrowth (SIBO). (Humans don’t produce hydrogen gas – only bacteria do.)
Rifaximin (550 mg 3 x’s day) for two weeks in combination with a low sulfate/sulfide diet completely eliminated the bloating, abdominal pain, constipation and foul gas she’d experienced after eating for decades. Her LDN was also increased. She was rewarded with another 25% decrease in POTS symptoms and a 43% decrease in MCAS symptoms.
The next two IVIG infusions further reduced her body pain, weakness, vertigo, ability to eat and facial changes. Then she reached a plateau; further infusions had no effect.
After 10 IVIG treatments, a tilt table test found that her POTS was completely gone. She needs to stay on the IVIG: without an infusion at least every five weeks, she starts to decline. The doctors aren’t done with her yet. At the time of the publication, they stated that they plan to continue the LDN and IVIG and add new mast cell treatments in the future.
The patient reported:
I feel like I won the lottery last year by discovering LDN, IVIG and SIBO treatment. LDN made me feel noticeably happier, more energetic, in less pain and with better digestion (and these things got better with each dose increase). IVIG was an absolute miracle and within a week gave me a life back, with a huge improvement of numerous symptoms, most importantly fainting, nerve pain and delayed pressure angioedema.
But I still had daily crippling stomach aches and more gas than a field of Holsteins until I took the rifaximin. I can’t believe I went decades feeling so bad when I only needed 2 weeks of antibiotics and a low-sulfur diet!
Now I’m back to standing, eating, sleeping, working, living and feeling exceptionally lucky.
The doctors believe that mast cell activation – not autoimmunity – was most likely driving her hyperadrenergic POTS. They proposed that mast cells activating near autonomic nerves were tweaking her sympathetic nervous system – a similar idea to Van Elzakker’s proposal that localized infections or inflammation near the vagus nerve is driving ME/CFS patients’ symptoms. It’s also not far from Dr. Pridgen’s hypothesis that a herpes simplex virus infection in multiple parts of the body is doing the same.
The authors reported that their case report established a number of firsts:
- the first time IVIG has been shown to lead to significant and sustained improvements in mast cell activation syndrome (MCAS).
- the first reported case of LDN improving POTS and MCAS symptoms.
They hypothesized that the sustained sympathetic activity caused by mast cell activation suppressed the peristalsis in her gut – the wave-like activity that pushes the contents of the gut canal forward. That “dead gut” then led to bacterial overgrowth, SIBO and leaky gut. The leaky gut then further tweaked her mast cells.
They believe the elimination of her SIBO and thus her leaky gut probably helped reduce her mast cell activation. In fact, they held out the possibility that her SIBO and the subsequent leakage of gut materials into her blood stream may have sparked the mast cell activation in the first place.
The POTS Gut Group
Goodman has made it his job to raise awareness around the gut issues in POTS. He reported he’d successfully treated 50 POTS patients with Sjogren’s Syndrome (SS) with IVIG and that IVIG had been dramatically successful in resolving the severe gut problems of another POTS/MCAS patient who had been to the emergency room over 250 times in 15 years for severe abdominal pain and diarrhea.
IVIG can be very helpful but noting how expensive and hard to get IVIG is, the authors emphasized how helpful LDN – an inexpensive drug seldom used in gut issues and POTS – and antibiotics can be in these diseases. Of 11 patients trying LDN, almost 80% reported an improvement in their gut symptoms. After one patient stopped LDN, his problems with standing, body pain, itching (pruritis), hair loss (alopecia), GI symptoms and fatigue returned. These symptoms subsequently subsided after he went back on the LDN.
Goodman also found high rates of SIBO in his patients with gut issues. A chart review of 33 POTS patients with gastrointestinal issues indicated that almost 70% tested positive on the lactulose breath test. Antibiotics improved the GI symptoms in 2/3rds of the patients given them (10/15). (If methane and hydrogen sulfide were present, neomycin was added to the Rifaxamin.)
The Group’s Takeaways
- POTS and MCAS can produce a wide variety of symptoms. Physicians should be aware of that and be open to diagnosing these illnesses.
- POTS does not just cause problems standing. It can also cause severe problems with gut motility, leading to IBS and small intestinal bacterial overgrowth (SIBO). If antibiotic therapy works in POTS, and then the patient relapses, consider that POTS-induced gut motility problems may be present.
- Given the fact that treatments for hyperadrenergic POTS are often not particularly successful, more doctors should consider MCAS treatments in this group.
- Combination therapy (IVIG, LDN) should be attempted.
- If SIBO is present, attempt antibiotic therapy.
Health Rising’s Takeway
- Keep up on the research, keep exploring treatments and find a good doctor! This person self-diagnosed her MCAS and then made her way to a good doctor. That was what made the difference for her.
About the Author: ProHealth is pleased to share information from Cort Johnson. Cort has had myalgic encephalomyelitis /chronic fatigue syndrome for over 30 years. The founder of Phoenix Rising and Health Rising, he has contributed hundreds of blogs on chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort’s and other bloggers’ work at Health Rising.