Thursday, July 30, 2015

Occams Razor: Lyme and Mast Cells


A 38 year old female who lives in the Pittsburg area had a purplish rash appear on her calf in the summer of 2013. The rash expanded. The calf became red, swollen, warm to the touch and very painful. She sought care at the local emergency room. She recalled a tick bite on her leg a month before, sometime in May, but thought nothing of it at the time. (She dearly wishes she knew then what she knows now). The doctors at the hospital thought she had either cellulitis, an infection of the fatty tissues under the skin, typically caused by strep or staph bacteria or a blood clot (DVT). She was given a single dose of an IV antibiotic. The ultrasound scan showed a blood clot: the infection hypothesis was disregarded. She was sent home from the hospital 2 days later with a prescription for a blood thinner. While in the hospital she felt generally lousy and had a low grade fever; these symptoms were dismissed.

She was discharged home and she promptly developed a collection of alarming symptoms. She had a stiff neck, chills, fevers - now to over 102 and a dry cough. She had a spinal tap and blood studies. The findings were elevated liver function tests and a low platelet count. She was given steroids and sent home with "asceptic meningitis." The term is a misnomer. Asceptic means devoid of germs. Asceptic meningitis is synonymous with viral meningitis. The spinal fluid was not entirely normal: a few white blood cells were seen and the protein was a little high, nonspecific findings. No evidence of bacterial meningitis.

Sent home after another 2 day admission she developed profound and generalized weakness. She soon found herself in a wheelchair. She developed strange cognitive deficits finding it hard to communicate. And she developed labored breathing: she was gasping for air for no good reason. A recent chest Xray was normal. She started to have random wandering or migratory joint pains: a hip one day, a knee the next and then a wrist and fingers and so on.

She went to her family doctor who ordered a Lyme test. The results were CDC positive: positive EIA first stage followed by positive Western Blot, IgM only. Her family doctor consulted a well respected fount of the best, current medical information: "Up To Date," and dutifully prescribed a 3 week course of doxycycline.

Instead of getting better she got worse. Now she complained of head and facial swelling, headaches, severe sensitivity to light and sound, disabling - bone weary exhaustion 24/7, numbness and tingling, loss of balance, neck pain, abdominal pain, nausea, forgetfulness, trouble speaking, flulike symptoms and severe drenching night sweats. This on top of worsening, diffuse pain involving large, medium and small joints - variable and asymmetric.

Her family doctor referred her to specialists: Neurology, Rheumatology, Hematology (all the -ologists): nothing found. Then she was referred to psychiatry. The psychiatrist said it was not in his field: she was medically ill --- with something.

She made the rounds: Mayo, Johns Hopkins, a few others and then me.
She transferred from a wheelchair to a chair on the other side of my desk. As she recalled her story she appeared severely short of breath, gasping between phrases. (I wanted to give her IV Mepron - no - not literally).

Needless to say, I proceeded with my workup.  Her neurological examination was abnormal. Her limbs were weak, especially on the right. Her reflexes were abnormal and she exhibited a Hoffman's sign.  She was unable to sense cold on her feet or feel a tuning fork vibrating against bones in her feet. She had a loss of position sense. She could not tell whether a wiggled big toe was pointing up or down. Her gait was abnormal and she failed a Romberg test (put your feet together and close your eyes) tumbling to the right.

Laboratory testing was negative for coinfection by serology (antibodies) but a stained drop of blood on a slide revealed parasites within red blood cells.

We know the patient was misdiagnosed by doctors, initially fixated on cellulitis vs blood clot. In fact the apparent cellulitis was the product of a very aggressive EM rash presentation. The blood clot was a secondary effect of pressure on blood vessels within the calf. Spinal fluid is frequently glossed over when typical bacterial meningitis (like pneumoccocal) is not present. The "viral" meningitis was in fact Lyme meningitis which might have been evident if different tests were done. The Lyme section in Up-To-Date is written by orthodox IDSA, 2006 panel members. The specialists seem to never diagnose Lyme correctly because they are working within a different box with a different set of rules. The neurologist never seem to understand: Lyme attack many facets of the nervous system causing bizarre - disconnected presentations. Doctors are frequently hammers in search of nails. For rheumatologists the nail is fibromyalgia. Sadly, everything about this case is "typical," something I see over and over again. This patient was needlessly punished, robbed of quality life --  because of a childish squabble led by a troupe of academic physicians who are now being challenged on their home turf by a new kind of Lyme clinic at Johns Hopkins.

After aggressive therapy for Lyme and coinfections for nearly a year and a half she felt much better, stopped treatment and was "lost to followup."

This April this year she called me. Another tick bite. Attached for only a few hours at best.
I called in a 3 week course of doxycycline.

Unfortunately, the bottom fell out and she became severe ill once more. 
In addition to the usual therapy, 2 months ago I tried something else and she is feeling so much better, quality of life restored.

I have become a bit of a hammer looking for nails -- mast cells. It is the only way I can get a handle on this disorder. More often than not these cells are major players.
And now I take a major detour.

In front of me is a consultation note from a hematology professor from the University of Minnesota, Dr. Lawrence Afrin. A brilliant man. In all fairness, the note discusses a patients who really did not get better with a year of intravenous Rocephin. This patient's story is somewhat different. She has suffered with years of POTS, arthritis, thyroid disease, small fiber neuropathy, cognitive dysfunction, brain MRI showing white matter disease, unexplained abdominal pain, vomiting, discolored feet, sleep apnea - obstructive and central, blood clots, pelvic pain syncope and other unexplained symptoms.

The doctor describes her highly positive review of systems:  she endorses a wide range of intermittent, chronic/recurrent, waxing and waning issues, mostly subjection (occasionally objective) which include fevers, flushing, feeling cold, fatigue (often to the point of exhaustion), malaise, headaches, diffusely migratory aching/pain, diffuse migratory pruritus (itching), unprovoked soaking night sweats, unprovoked fluctuations in appetite, eye irritation, episodic loss of focus, nasal congestion, swooshing in head...the list goes on.

Laboratory testing showed elevated 24 hour urine 11-beta-prostaglandin-F2-alpha level. He states that this is not a definitive test; he wants to make the diagnosis of mast cell activation syndrome stating "there is no other human disease he is aware of" that can cause all of these issues. He pedantically discusses an array of diagnostic tests and genetic variables that makes my head spin.
This single progress note could be made into a chapter in a text book, (one that would be both difficult to read and be understood by the non-specialist practitioner).

The author evokes Occams Razor (the idea that the simplest explanation is usually the correct one): he strongly doubts that she ever had Lyme disease. He states that IgeneX is an outlier lab, the only lab to find "evidence" of Lyme when other laboratories cannot. Not true. A recent peer reviewed study from Columbia University completely vindicates the unfairly maligned lab. killing the messenger is always easier -- when you don't want to hear the message.

Learning about mast cells and their role in inflammation has been eye opening for me and helping many patients.  Mast cell disorders, as discussed in current medical literature, are seen as an increasingly heterogeneous assortment of disorders. Mast cells are heterogeneous themselves. Lyme and other infections  trigger mast cell activation and this is supported by peer reviewed studies.
Lyme in many ways is a disease mediated by the immune system. These odd spirochetes with lippoproteins jetting out from a double membrane cause disproportionate immune responses: cytokine storms and ill-defined autoimmunity are frequently pointed to. In my, perhaps, overly simplistic "simple country doctor" brain I imagine a scenario where all roads lead to Rome. Immune repsonses - cytokines, helper cells, killer cells, antibodies, complement (effector mechanisms - the business end of immune responses) all converge on mast cells. These cells and their attendant mediators play a large and under appreciated role in what we experience as inflammation.

Perhaps tendencies for excessive mast cell activation are largely genetic. The doctor rightfully discusses influences from genetics and epigenetics yet to be understood. All human disease is the product of genetic tendencies combined with environmental stimuli (frequently infection).  Inflammation is always a double edged sword. Without inflammatory responses we could not survive the hostile world of microbes and mutated cells that would do us in. On the other hand, all chronic diseases, like heart disease and diabetes are now seen as disorders of inappropriate chronic inflammation.

A new tool. A new synthesis. My message for the much-smarter-than-me professor is: there is at least one more disease (other than straight mast cell disease) that can explain your patients seemingly crazy symptoms. Occams Razor is only a suggestion.  Look deeper.

8 comments:

Andraste Errini said...

I had skin rashes following the blood vessels closest to my skin at the same time that I had unbearable joint pain - this in my 20's, at the height - introducing the end - of my athletic career. I recall having a mast cell attack at work; I worked in a community health center and was seen by medical staff there, for "mast cell response." Dx: stress. Two years' later I had my first psychiatric break. I then spent 30 years being treated for depression and fibromyalgia. It was not until I reached the local office of the Fibromyalgia & Fatigue chain that I was diagnosed with Lyme disease. Their diagnostic decision tree tests last for abnormal NK-cells, and, if those are abnormal, the very last thing they test for is Lyme disease. I will forever be beholden to Dr. Jacob Teitelbaum, who authored that diagnostic decision tree. Yet it was not until some point after I was hospitalized with 12 pulmonary emboli that I was diagnosed with Lyme disease. I have met both Igenex and CDC criteria for positive test results. Try explaining to the hematologist the concept of "sticky blood." I am on SSDI now, can no longer afford my very-expensive trips East to my very expensive LLMD, and my long-term primary care physician is scared to death to put me on antibiotics. Does anyone know any magic words? I'm in WA State

AIDAN G WALSH said...

magic words 'undiagnosed' Ehlers Danlos Syndrome type(s) with MCAD Mast Cells Activation Disorder London Hypermobility Unit Dr Rodney Grahame...

Crouton Sandwich said...

some variety of Ehler Danlos, good luck getting diagnosed its nearly as tricky as getting a lyme diagnosis

Liana Dicus said...

This is heart wrenching, what is happening to us all. Thank you, and congratulations for getting through the shameful legal situation! I am in forever debt to you for providing so much medical information and creative musings to help us as a community.

I am a 'bendy' person, have the "suggestive" Ehlers Danlos genes. I hurt my back, stretched some sacro-iliac facet ligaments some years ago and those facets sublux a lot (I do need better core strength). The point is my low back area will "flare" in addition to the subluxing, which has become a beacon for when my system is inflamed, and I have the accompanying fatigue.

I have low saliva cortisol (diurnal, x 4 test), and a mildly elevated TSH. I started the NDT (natural dessicated thyroid-NatureThroid) and was relieved of all depression, felt good for a few weeks, then crashed. I stressed my adrenals. I started on low dose, physiological doses, of Hydrocortisone. I have my Life Force back. (I have been treated for months with high dose Doxy-then 3 months of rotating Flagyl, Ceftin, Zithromax-the latter did not make any difference,and I had Lyme for many years, have MTHFR, take methyl B vitamins, FIR sauna, Minerals, high chlorophyll drinks, amino acid complex, and digestive enzymes). I am taking I3C (Indole-3-Carbinol) for a mid cycle PMS and it helps, but it metabolizes my cortisol (!), so I use a little more HC as needed. I take HC 10mg in am, 5mg at noon, other times, PRN). I have the "slow" metabolizer genes, so this makes sense to have issues with estrogen. It is complicated, as we all know. (Look into the research science on Cortisol and PMS/Nausea in early Pregnancy/Post-Partum depression, etc)
I am so grateful I didn't take high dose steroids (for my chronic sinusitis) before getting diagnosed with Lyme, but it could be so supportive in this low dose while being treated! I plan on taking low dose for a few months to rest my adrenals-it was amazing, the first dose actually made me relax-I was clearly cranking out last ditch life saving adrenaline to exist upright.
Bottom line, our sensitive glands are like rice paper windows that sense the wind and are being "blown out" by infection and toxins.
HC (and NDT-the T3 Conversion issue is just as important to recognize-even in euthroid patients) has saved my life. Please consider this for your patients, and I would enjoy hearing your thoughts as a care provider. I am an RN and feel like after 15 years that I have come out the other side (dinged up) from the wormhole of this modern affliction. Thank you, again.

WLP Romania said...

waiting your next post. thanks.

angi said...

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good luck.

Unknown said...

I've been in this dx limbo for years. In 2007 I found a tick on my head. I took it off and never had any symptoms or rash from it. 2008 I got off the exercise bike and heard a loud CRACK in the left knee. Sadly no health insurance at the time and it took a year to be seen by a doc. I got refered to a ortho for surgery from torn cartilage. He scoped it. In 2009. Because I left it torn for so long it retorn, then for favoring the left for so long the right tore. I was sent in for 2 more scopes. When I woke up from the last surgery I noticed my legs were numb, have been since. I developed arhtitis in both knees. I have not had any other tears since. A year later in 2011 I had a sudden and violent neurological attack. It started in the spine with electric shocks going down the spine and increased tingling with moving the neck down, with blurryness and double vision in one eye, with dark spots in the field of vision. Increased numbness from what was normal for me, my left bicep starting visability pulseing like a heart. Nerve pain like someone was trying for a iv and missed. Then sudden massive numbness from the low back down, couldn't walk, was falling to the left side, couldn't move my legs, it felt like having 10 pound weights on my legs. I was using a walker. I couldn't say words, short term memory loss, dizziness. I was in the er they thought it may be lyme because of that tick bite. They send me to a lyme doc. She ran the western blot test sent to the ca lyme lab. What came back was a negative test. One number came back but they said "with years after possible exposure, this is a false positive". The lyme doc said this doesn't mean her standereds and the lab and ca is poor for dx lyme in her opinion. She started me on antobitcs. She said with neurological symptoms and knee pain that had to be lyme arthitist. She said I have lyme. About 2 weeks later about 6ish weeks of symptoms all the symptoms vanished. She told me that because my knee hurts that I need at least a year of antiboitcts the kness should be totallt healed. A year of antiboitcs nothing changed. She sent me to a otho who said their was no sign of a disease process that my kness were just simple arthitis from surgery. I never had a good realanship with that lyme doc. I stopped seeing her. As a result of long term antibotics I now suffer from very bad GERD. I took me years to find a doc that would see me. I kept getting refused from docs saying they don't treat lyme disease. Finally I found a good doc. He looked at all my symptoms, and what the lab said and he didn't think I had lyme but didn't really no what to do with me. In may of 2015 I had a second major attack all same symptoms. About a month of symptoms and they all vanished again. I was refered to a neurologist for possible ms review. He did a brain mri and found deep white matter non specific lessions T2 with Flair, in the Left Parietial Ocipitial Junction (sorry if that is spelled wrong). I got the mri and was then told my neuro was out of town for the next few months and my follow up is for December. My family doc told me this isn't where ms should develop. So now I am unsure what I am looking at. I don't have chronic migrains, diebities, chronic hypertention. So is this ms or lyme?

Unknown said...

I am a patient of Dr. Afrin's. I was a former Lyme patient with a CDC positive diagnosis from Igenex. I did over a year of orals and IV abx but continued to decline. I am from the Maryland area and saw many LLMDs (though was not a patient of yours). In my opinion, Igenex misdiagnosed me and I hope that you consider this as a possibility. Many other Lyme patients I know have also had this experience. They just never saw any kind of improvement and then abandoned treatment because it wasn't working. Please consider that those who do not see results (ever) may be misdiagnosed. I certainly support Lyme treatment when it proves beneficial. However, Lyme treatment is in almost complete opposition to MCAS treatment. Enhancing the immune system to fight infection versus calming it to control mast cell activation. Since there is a suspicion that MCAD could be prevalent in 7-17% of the population, I encourage you to test for this, (if not first) before pursuing Lyme (when someone presents with a vague history). My MCAS got 1000 times worse after Lyme treatment and I was in a constant state of anaphylaxis. I do believe that there are exogenous factors like Lyme that may play a part in our health but I hope that the safest and least invasive route could be explored first. Lastly, don't get me wrong, Lyme and MCAD as I've sure you've seen are certainly not mutually exclusive. Please read my story. https://www.mhealth.org/blog/2015/august-2015/struck-by-mast-cell-activation-syndrome-jennifer-credits-m-health-expert-with-saving-her-life