Need help with perplexing suite of symptoms

[shoshinsha]

Hi everyone,
I'm writing for my wife, who has been dealing with *something* for the last year that seems to be POTS/CFS. I say "something" because her symptoms overlap with those conditions, but many of her experiences seem out of the normal spectrum and we don't know what to do. Here's a quick rundown:

My wife:
-22 years old (21 at time of symptom onset)
-5'8", 140lbs., good diet
-No prior notable medical history (not a very athletic/coordinated child, but active and healthy)
-Very healthy prior to onset (in a year and a half, I never saw her get sick until symptom onset)
-Prior history of some substance abuse (alcohol, tobacco, marijuana, occasional painkillers) in teen years
-Survivor of abusive parenting (more emotional/psychological than physical, resulting in mild PTSD)
-Prior use of anxiety and depression meds when life situation was difficult
-Stopped all meds and substances 6-8 months prior to symptom onset due to being happy with life
-Graduate student with moderately high-stress working life

Lead up to symptom onset:
-Happened approx. one year after moving to Oklahoma from Texas (grew up in Virginia)
-No prior illness, injury, or other trauma (that we noticed, anyway)
-About 9 mos. prior, had sudden and severe hives (about 3-4 bouts over a couple months, none since)
-Had a bout of sudden and severe lightheadedness at work about 6-8 mos. prior (lasted only one evening)
-Lost approx. 20lbs. over ~3 mos. earlier in the year, not trying, no diet change
-Continued losing weight (approx. 10lbs.) while eating same after onset of symptoms
-Began regaining weight approx. 6 mos. after symptom onset
-Sudden onset (went to bed well, woke up with chronic nausea and dizziness, we thought she was pregnant)
-Nausea primary symptom for first 2 weeks, after which dizziness seemed to become more prominent

Vitals:
-Chronically low blood pressure (usually runs ~95/55, give or take)
-Chronic tachycardia (~75bpm supine, ~88bpm sitting, ~100-135 standing depending on the day)
-Note: when we control her HR and BP to keep them in the normal ranges, she often still has symptoms

Symptoms: (symptoms fluctuate drastically, with housebound days/weeks and almost normal days/weeks):
-The following symptoms are worsened by standing, but may occur in any position, and may occur even when her heart rate is low and her blood pressure is relatively normal (anxiety can exacerbate these):
---Nausea
---Dizziness
---Spaciness/brain fog
---Vertigo (described as feeling like the floor is moving up and down, just started a few months ago)
-Motion sickness (used to not get sick in car, now gets sick very easily and sickness persists hours)
-Extreme fatigue (especially following activity)
-Sensitivity to stimulation (retail stores, hospitals, crowds, noise, motion, stress, etc. make everything worse)
-Immune suppression? (symptom onset last Nov, then got sick 4 consecutive times between Christmas and Valentine's day, only sick once since then with cold I had)
-Lower-leg mottling (standing for prolonged time causes knee/ankle skin tightness and purple/pink color)
-Temperature intolerance (esp. heat makes things much worse)
-Headache (rise in headache frequency the last month, minimal headaches prior)
-Sound sensitivity (loud noises can trigger nausea)
-Seasonal allergies (didn't have any before this year)
-Chronic constipation
-Chronic, recurrent bacterial vaginosis (3-5 occurrences over ~6 mos.)

Common symptoms she does NOT have:
-Pain/myalgia
-Muscle weakness
-Decreased appetite (to the contrary, she eats a LOT)
-Vomiting
-Actual fainting (only pre-syncope)
-Transient hypertension
-Tremor
-Loss of motor coordination

Medical treatment/assessment:
-Seen by endocrinology, cardiology, neurology, etc. (most are conservative, unfamiliar, unhelpful)
-EKG (normal)
-Echocardiogram (normal)
-Pelvic-abdominal ultrasound (normal)
-Brain MRI (normal)
-Standard blood panels (normal)
-Morning fasting cortisol (slightly low)
-Lupus (negative)
-Thyroid (negative)
-Lyme (unclear, probably negative)
-Iron (normal)
-Tilt test (positive)

Medication history:
-Birth control (symptoms seem to have vague correlation with menstrual cycle)
-Florinef (0.01mg, may help slightly, hard to tell)
-Delayed-release potassium (for florinef)
-Sodium and water loading (~5g & 3 liters daily) (may help slightly, hard to tell)
-Thigh-high compression stockings (no help)
-Midodrine (made her feel awful, bedridden until it wore off, blood pressure non-responsive)
-Phenylephrine (made her feel awful, bedridden until it wore off, blood pressure non-responsive)
-Propranolol (nonselective beta, helps somewhat, but inconsistently, and sometimes not at all)
-Metoprolol (beta 1 selective, made her feel awful, blood pressure dropped a lot)
-D-Ribose (tried for 2-3 weeks, didn't seem to help, may have made her feel worse)

Conclusion:
Whew! That's about it for now. I'm sure I'll think of more later. The most perplexing parts of this are:
-Why do her symptoms NOT seem restricted to when her BP is low and/or HR is high?
-Why the weird reactions to medication? (midodrine = bad, propranalol = mildly good, florinef = neutral, etc.)
-Why are these new, atypical symptoms appearing (vertical vertigo, motion sickness, sound sensitivity)?
-Why is there no apparent onset event? No illness/injury event, no family history, etc.
-What does she actually have that combines all of these symptoms?
-She was feeling relatively good and building up an exercise regimen the last few months, then suddenly something just knocked her completely out and she can barely stand the last few weeks. Why?
-What can we still do/try?

I know that's a lot to read, but we're pretty desperate over here. Thanks to any and all who read!

 

[Martial]

I am not an expert on other causes of CFS but have you ever looked into Lyme disease? Definitely sounds like something is affecting her autonomic nervous system and obviously some degree of POT/S however that has many causes.

 

[Jonathan Edwards]

I think everyone is probably agreed that there is no single disease called CFS and although there are a lot of people who have rather similar 'typical CFS' or ME there are almost certainly a lot of people who could fall under this category who have unrelated diseases with the only common feature being nothing specific to make a diagnosis and a bunch of similar symptoms. So CFS might turn out to be the closest to a diagnosis available.

However, I am struck by the dominance of nausea without vomiting, plus true vertigo - although the initial phase is described just as dizziness. The commonest cause of vertigo in young people is a mysterious thing called acute vestibular neuronitis. It usually lasts for a few weeks but can hang around for longer. It is said to be 'viral' but I think only because nobody knows what it is. It is very common. I have had it and so has the colleague who took over my job when I retired. It does not occur in lots of people at once like a normal infection. One person has it at a time. Normally, right at the start there is severe vertigo so that even lifting your head off the bed makes you feel sick and the world go around. All you want to do is hide in the dark.

This story does not sound exactly typical for vestibular neuronitis but with these mystery diseases things are not always as typical as the books say. I would just ask whether she has had caloric testing to assess her vestibular nerves. This is done by running slightly hot or cold water into the outer ear while looking for nystagmus eye movements. In a normal person the temperature of the water makes the eyes flick from side to side because the endolymph in the semicircular canals starts convecting around and the vestibular nerve thinks you are spinning around. I had this done after my episode of 'VN' and on the right side nothing happened at all. I was told that my right vestibular nerve was defunct and probably would stay that way. Fortunately, the left one does the job and in fact you can get used to having no vestibular function much, unless it is pitch dark. It has never bothered me since.

So I just wonder if this is the after effect of a vestibular neuronitis and if it is I think a caloric test is likely to show something. A neurologist may have done this but it tends to get done in ENT.

 

[brenda]

@
shoshinsha

Any sudden onset of neurological symptoms need a thorough checking for Lyme Disease to rule it out and unfortunately laboratory testing is unreliable. Which lab was used and what were the results please? Some Lyme Literate Medical Doctors, use a clinical diagnosis because of the difficulties with labs. The sudden onset and weight loss were part of my own experience of the disease.

 

[Valentijn]

@shoshinsha - Could you elaborate on the Lyme results? I picked up Lyme about 20 years ago while living in rural southern Oklahoma. A western blot came up completely negative, but a Elispot-LTT came up positive, and my reaction to antibiotics seems to confirm an infection by spirochetes as well.

The problem is that the standard Lyme tests only look for borrelia burgdorferi, even though there are at least a dozen borrelia strains known to infect humans. And even when testing someone with borrelia burgdorferi, the standard tests have a huge false negative rate - up to about half of patients who have confirmed infection will test negative.

The Elispot-LTT is less picky about the type of Borrelia being detected, and has been verified in published research to have 89.4% sensitivity and 98.7% specificity. So about 10% false negatives, and only 1.3% false positives. Though results haven't been duplicated (or contradicted) yet by independent researchers.

 

[zzz]

@shoshinsha - Every single one of the symptoms you describe, both in the "Lead up to symptom onset" and the "Symptoms" section, is a known symptom of Lyme disease. This of course does not prove that your wife has Lyme disease, but I think that it's a possibility that has to be taken very seriously. Good testing is essential; @Valentijn has given excellent advice here. The first symptom is often very revealing, and in this case it was the sudden and severe hives. The rash caused by Lyme disease may look like hives, and in some cases may be indistinguishable from true hives. The apparent hives sometimes come and go until the underlying trigger is resolved; this sometimes takes a couple of months or more.

There is tremendous overlap between the symptoms of Lyme and CFS, and it is often difficult to tell them apart. The one symptom present in CFS but not Lyme is PEM - post exertional malaise. If your wife overexerts herself on one day, does she feel much worse on the next day or the day after? If so, this is an extremely strong indication that she has CFS. But Lyme disease and CFS are not exclusionary; they often occur together. And if a PEM reaction to overexertion is not present, it is much less likely that she has CFS, especially considering how severe her other symptoms are.

It's worth noting that Lyme disease can cause POTS.

I'll try to answer your question as best I can.

-Why do her symptoms NOT seem restricted to when her BP is low and/or HR is high?

Many of these symptoms are completely independent of BP and HR. Many of them are straightforward neurological symptoms.

-Why the weird reactions to medication? (midodrine = bad, propranalol = mildly good, florinef = neutral, etc.)

People have all sorts of reactions to medications; there is no standard list that works for everyone, and it is very individualized. You may have better results with the midodrine if you start out with a much lower dose and work up slowly.

-Why are these new, atypical symptoms appearing (vertical vertigo, motion sickness, sound sensitivity)?

These actually aren't atypical, in either CFS or Lyme. Also, these illnesses often evolve with time, and symptoms can come and go.

-Why is there no apparent onset event? No illness/injury event, no family history, etc.

I would say that the apparent hives are the onset event.

-What does she actually have that combines all of these symptoms?

My best guess (and it is just a guess) is Lyme disease, as it can manifest all these symptoms. She may also have CFS, as described above.

-She was feeling relatively good and building up an exercise regimen the last few months, then suddenly something just knocked her completely out and she can barely stand the last few weeks. Why?

Especially with Lyme disease, symptoms can be cyclic. But if she has CFS, this may be severe PEM from overextending herself from the exercise regimen.

-What can we still do/try?

I would recommend first of all, getting the tests that @Valentijn recommended, and secondly, finding a Lyme Literate Medical Doctor (LLMD), who is a doctor who understands all the complications of Lyme and how to treat them. If you have trouble getting the proper tests done, you may have to do the second step before the first. And as @Valentijn mentioned, even the best test has a 10% false negative rate, so in consideration of your wife's symptoms, I think that a consultation with an LLMD would still be warranted.

Good luck!

 

[nandixon]

@shoshinsha

Has mastocytosis been ruled out?