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Lisa Klimas

I'm a 35 year old microbiologist and molecular biologist with systemic mastocytosis, Ehlers Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome, Adrenal Insufficiency, and an assortment of other chronic health issues. My life is pretty much a blast.

Neuropsychiatric features of mast cell disease: Part 1 of 2

The fact that psychiatric symptoms occur as a function of mast cell disease on the nervous system is common knowledge to patients but less acknowledged by providers.  A significant population of mast cells is found in the brain in close association with both blood vessels and nerve cells.  Mast cells are present in large numbers in the hypothalamus, which regulates stress response, emotion and cognition; the amygdales, near the pituitary gland; and the thalamus.  Lesions and structural changes in the thalamus have previously been associated with altered perception of pain and emotional reactivity.

One study found that in a group of 88 patients with indolent systemic mastocytosis (ISM) and cutaneous mastocytosis (CM), 75% reported depressive symptoms.  In another study, a group of 288 mastocytosis patients had a prevalence of 60% depressive and anxiety-type symptoms.  The depressive symptoms seen most often in mastocytosis patients are affective and cognitive symptoms (depressed mood, low motivation, feelings of guilt and failure; and anxio-somatic symptoms (physical and mental effects of anxiety, insomnia).  Psychomotor difficulties (slowing of thought processes and/or neurologic control of movement) and lack of insight were rare in these patients.

Depression is often assessed using the Hamilton Depression Rating Scale.  This tool may not be ideal for use in mast cell patients because the somatic symptoms correlated with depression are often the same as physical symptoms of mast cell disease.  When excluding symptoms that could be from mastocytosis rather than depression, patients still had a high prevalence of sadness and loss of motivation.

One mastocytosis cohort reported 38.6% had cognitive impairment of some kind. Inability to focus and pay attention is the cognitive symptom most commonly reported by mastocytosis patients.  This was not linked to depression, age, education or staging of mastocytosis.  Importantly, it was also independent of amount of antihistamine use.  Memory impairment was also not related to age or education.  Cognitive difficulties were found to be much more prevalent in mastocytosis patients than in other chronic disease populations.

Fatigue is a common neuropsychiatric symptom for mast cell patients and has been seen in populations with both mastocytosis and mast cell activation syndrome.  Patients who have moderate to severe fatigue often experience pain and cognitive deficits.  The level of fatigue can be disabling as it makes it difficult to focus or perform even simple tasks.

35% of mastocytosis patients in one study reported 35% had either acute or chronic headaches.  37.5% had migraines, while 17.2% had tension type headaches.  Headache patients often reported episodic flushing or itching at the time of the headache. In the migraine group, 66% experienced aura symptoms.  Overall, 39% of patients in this group with or without migraines experienced aura symptoms, usually visual.

Exaggeration of the stress response could explain neuropsychiatric symptoms in mast cell patients. In one population, 42% of patients perceived their stress level to be high. Persistent stress response could lead to negative emotions.  These symptoms could be reinforced by mast cell hyperactivity in the brain, which can affect stress response, emotionality and cognition.

References:

Georgin-Lavialle S, et al. Mastocytosis in adulthood and neuropsychiatric disorders. Translational Resarch 2016; x:1-9.

Georgin-Lavialle S, et al. Leukocyte telomere length in mastocytosis: correlations with depression and perceived stress. Brain Behav Immun 2014; 35: 51-57.

Moura DS, et al. Neuropsychological features of adult mastocytosis. Immunol Allergy Clin North Am 2014; 34(2): 407-422.

Moura DS, et al. Depression in patients with mastocytosis: prevalence, features and effects of masitinib therapy. PLoS One 2011, 6: e.26375.

Moura DS, et al. Evidence for cognitive impairment in mastocytosis: prevalence, features and correlations to depression. PLoS One 2012, 7: e.39468.

Smith JH, et al. Neurologic symptoms and diagnosis in adults with mast cell disease. Clin Neurol Neurosurg 2011, 113: 570-574.

The Devil’s Arithmetic

When I was in grad school, I took immunology. I still have my textbook and refer to it sometimes, my crowded notes in the margins. The chapter on allergy and anaphylaxis is highlighted in green, somehow aggressively bright after eleven years.

It’s kind of amusing to recall this time in my life, before every mast cell activation pathway had been hammered into my brain. There’s also some black humor in reading about how IgE activation is the allergy pathway. You know, THE allergy pathway. This book doesn’t cover any other pathways. As if you cannot possibly be allergic to something without IgE.

That’s the problem, of course. This is what most healthcare providers or science majors learn in school. They learn about allergy and anaphylaxis, but they learn about the textbook description which invariably refers to IgE mediated food anaphylaxis. They learn about peanut allergy.

I don’t have a peanut allergy. I literally don’t have a single food allergy that displays the hallmark swelling/closing airway that people expect. But I have major food allergies, some bad enough to require epinephrine, IV Benadryl, Pepcid, Solu Medrol, Zofran and IV fluids.

The problem is not just that I’m allergic to some foods. It’s that I’m not always allergic to the same foods as I was the day before. Or the same medications. Or the same environmental exposures. My reactions on a given day are the cumulative product of the amount of irritation my mast cells have experienced in the previous day or two. There is always a running tally in my mind.

There are a lot of analogies and models used to describe mast cell attacks both to patients and to people who don’t have them. I have always thought of it as a bank. You make deposits and you make withdrawals. Like this:

For the sake of simplicity, let’s assume you have $100 in a bank account. Any activity that can cause mast cell activation has to be paid for. The cost is proportionate to the amount of activation. Getting a splinter: $2. Being hot: $10. Being in direct sunlight: $10. Standing up for 20 minutes while being hot in direct sunlight: $35. Cardiovascular exercise: $40. Arguing with your spouse: $60. Moderate pain experienced in your day to day life: $50. A painful medical procedure: $70. Mild cold: $40.

Some things are too costly to ever attempt.  Undercooked egg whites: $9000.  Massive bleach exposure: $7500.

You can make deposits into the bank with medications and physical changes. Getting enough sleep: $30. Wearing loose, comfortable clothes: $15. Doing orthostatic manuevers before standing up: $10. Taking baseline mast cell medications on your normal schedule: $50. Eating food that is warm but not hot: $15. Monitoring your exercise and stopping for breaks: $15. Wearing a cooling vest on a hot day: $20. Oral Benadryl: $25. IV Benadryl: $50. Steroids: $50.

So you have this running tally in your head all day long. When you start getting close to $100, you get stressed. You know you can’t afford to spend more than $100. Things that you could have done four hours ago safely are no longer safe. Things you could eat on a day spent relaxing at home inside with comfortable ambient temperature cannot be eaten if your apartment is too hot or if you are in a lot of pain.

You are constantly trying to avoid running out of dollars before you can get home and go to bed. Part of this is because you don’t want to trigger a physical reaction. Part of it is that this phenomenon – allergies as a function of circulating histamine/mast cell activation rather than IgE – is hard to explain briefly to people who don’t have this disease. So people will see you on a super crappy day only being able to eat one thing at a party and then four months later, when your body is much less inflamed, will see you eat three things at a party. And then it’s a thing, because these people invariably think that you are faking/being overdramatic as if somehow it is worth the effort to “pretend to have allergies.” WHO FUCKING DOES THAT?

Cost for being around someone who gives you shit for not always having the same restrictions: $75.

So everyday, you get $100. Except this is the US and our banks hate us so we have overdraft. This means that you can spend more money than you have but then they charge a steep fee and so the next day, you don’t have $100. You have maybe $30 dollars. After overspending, it can take a few days to get back to baseline.

Sometimes it’s worth it. Sometimes you can sort of game your body into getting more than $100 out of a day. This is the purpose of premedication for procedures and surgery. This is the purpose of good sleep hygiene, eating safe foods, not getting stressed, taking medications appropriately and on a schedule. You can bank a little. Not as much as you can overdraft, but you can get ahead a little bit.

Today, I went to the supermarket to grab some things for lunch at work. They didn’t have organic apples that looked in decent shape. They had non-organic apples and my safe peanut butter/honey and my safe pretzel chips. I had to run through my entire day to determine how much physical activity and stress was likely to be in the rest of my day to figure out what I could (probably) safely eat for lunch.

It’s like this all day, every day. This math wouldn’t be hard except that it’s constant and unavoidable and controls my life.

I kind of can’t believe I have to write this post

Hi, everyone –

I found myself in a really strange situation this week and feel like I need to say something.

I write this blog both as therapy for myself and in an effort to help patients with mast cell disease and other conditions.  The details that I omit are sometimes left out for privacy and are sometimes left out for safety.

Some of the drugs mast cell patients take to manage their disease can be abused, including IV Benadryl.  While I realize that the majority of people who read this blog and take IV Benadryl use this medication responsibility according to their doctor’s instructions, the fact is that this is the internet and I don’t really “know” most of my readers.

I do not and will not discuss things like exactly how I get various medications that can be abused because that could endanger me.  If I tell you that a line of questioning makes me uncomfortable and you continue to press me, I will never interact with you again.  Period.

I have made a choice to share my life but that choice does not extend to minutiae regarding my treatments that could affect my personal safety.

Thanks,

Lisa

Derivative

I am not easily intimidated. I have been sick a long time. I am used to being around hospitals, doctors and sick people. I am used to reading lab work and pathology reports. I have seen a lot of people pull out of medical crises. I have seen my intestine attached to the outside of my body, emptied colostomy bags, packed my own incisions, accessed my own port. It takes a lot to scare me.

Waking up with a fever of 103.2 two days after dental work scared the shit out of me. It’s kind of funny in hindsight in a morbid way: infectious diseases microbiologist develops tests for bloodstream infections, gets bloodstream infection. But it wasn’t funny then. I am very even when I speak to providers who don’t know me because my life could literally depend on it. I was even that day, but it took a lot of effort.

I was discharged after a few days of antibiotics and continued them at home for another week. I called out of work, a rare instance of sick time rather than working from home, because I was so exhausted and winded that it was difficult to do anything. In 2014, when the shit really hit the fan, standing up was enough to make me sweat, my heart race and blood pressure drop. It felt like that again. Like anything but being in bed was too physically demanding and being awake was too mentally demanding.

In the days after discharge, I lay in bed thinking about deconditioning and POTS and anaphylaxis and what if I had to start all over again? There isn’t a word for what I was experiencing. If we had a word for the crescendo to blind panic, the choking and the blood pounding before you scream, that might be it. What if I got these nine months of improvement and this was it?

The first few days back at work were very hard, my blood pressure was low and my mouth still hurt a lot. I had appointments last week at the hospital and one of my doctors is pretty convinced that I had a true bloodstream infection that just didn’t culture because of the antibiotics. I slept most of this weekend. But things are coming back together.

This past year, it was easy to settle back into a routine, to prioritize certain things over the things I had always dreamt of pursuing. It feels foolish now to have done that. I cannot take for granted that the way I have felt is the way I will continue to feel. If I hadn’t been on antibiotics since the dental procedure, this story could have ended very differently, with my port being pulled and time in the ICU to treat a bloodstream infection and anaphylaxis and months of recovery.

Life is short. All important things are derivative of this. Every lesson is secretly the same.

Explain the tests: Complete blood cell count (CBC) – White blood cell count (Part five)

White blood cells, also called leukocytes, are key functionaries of the immune system.  There are several types of white blood cells and each is specialized for certain types of immune response.

White blood cell levels are useful for pointing to many conditions.  They can be high or low for many reasons.  They are commonly used to determine whether or not a patient has an infection.  A “left shift” in the white count indicates presence of high numbers of immature white cells, often called bands.  A left shift can occur for a number of reasons.  It is a natural response to infection as the body tries to make enough white cells to fight the infection.  A “right shift” refers to the absence or low level of bands, new white cells.  This indicates suppression of bone marrow.

Normal range for white blood cell count:

  • 0-11.0 x 109 cells/L

Types of white blood cells can be quantified as either a percentage of total white cells or as an absolute count.  Normal white cell count varies with age, especially neutrophils, lymphocytes and monocytes.

Normal range for neutrophil count:

  • 8-7.7 x 109 cells/L
  • 35-80% of total white cells

Normal range for eosinophil count:

  • 0-0.8 x 109 cells/L
  • 0-4% of total white cells

Normal range for lymphocyte count:

  • 8-4.8 x 109 cells/L
  • 18-44% of total white cells

Normal range for monocyte count:

  • 2-0.9 x 109 cells/L
  • 7-12.5% of total white cells

Normal range for basophil count:

  • 0-0.1 x 109 cells/L
  • 0-1.2% of total white cells

Explain the tests: Complete blood cell count (CBC) – High white blood cell count (Part seven)

High white blood cell count is called leukocytosis. High white blood cell count is often due to a healthy process, such as immune defense or inflammatory response after an injury.

Reasons for leukocytosis:

  • Infection response, especially bacterial infection
  • Inflammation
  • Physical stress and tissue death
  • Allergic disease
  • Proliferative diseases of white blood cells, such as leukemias

Conditions that cause tissue death and elevate white blood cells:

  • Physical trauma
  • Surgery
  • Ischemia
  • Heart attack
  • Burns

Allergic conditions that elevate white blood cells:

  • Allergic reaction, acute or chronic
  • Anaphylaxis
  • Asthma
  • Atopic disease

Inflammatory conditions that cause elevation of white blood cells:

  • Autoimmune diseases such as rheumatoid arthritis
  • Inflammatory bowel diseases

Medications that trigger excessive production of white blood cells:

  • Corticosteroids
  • Beta agonists

 

Explain the tests: Complete blood cell count (CBC) – Low white blood cell count (Part six)

Low white blood cell count is called leukopenia. Due to mast cell involvement in many bodily processes, leukopenia can occur for many reasons.

Reasons for leukopenia:

  • Bone marrow suppression
  • Disorder of white cell production or white cell precursors
  • Proliferative disease of other cell types in the bone marrow
  • Mechanical destruction of white blood cells, as in splenomegaly (swollen spleen)

Some conditions that interfere with making enough white blood cells:

  • Certain infections, such as tuberculosis, malaria, dengue fever, Lyme disease and viral infections
  • Sepsis
  • Nutritional deficiency, such as low copper or zinc
  • Nutritional toxicity of certain minerals, such as arsenic

Some proliferative diseases that interfere with making white blood cells:

  • Hodgkin’s lymphoma
  • Myelofibrosis

Conditions that affect white cell precursors:

  • Aplastic anemia
  • Myelodysplastic syndrome
  • Damage to precursors by radiation exposure or chemotherapy

Conditions that cause damage to white cells:

  • Splenomegaly, swollen spleen
  • Lupus

 

Medications that interfere with making enough white blood cells:

  • Immunosuppressants, like mycophenolate, cyclosporine and TNF blockers
  • Interferon preparations, like Betaseron
  • Other medications like clozapine, bupropion, minocycline, lamotrigine and valproic acid
  • Chemotherapy
  • Radiation

The unseen hand

I have spent a lot of the last several weeks trying to navigate the dark waters of mid-level care for a rare disease patient.  It is one of the trickier aspects of life with a disease like mine.  I need care and need providers to be cautious but I also need them to not be scared of my disease or they could refuse care.  When I’m shocking or having a serious medical event, it’s not really an option to refuse care.  But when something is serious but not life threatening, I have to tread carefully.  It requires just the right amount of education given confidently.  The tiniest twinge of voice, a catching of my breath while I’m talking about my disease, and they could easily walk away.

I got my tooth removed on Tuesday at a dental office in the same hospital where I receive all of my care.  The dental team was very good and took my special requirements in stride.  But I realized pretty quickly that this extraction was going to be harder than I had expected.  All told, it took three people two hours of actively trying to extract the tooth to achieve success.  EDS patients are often insensitive to anesthesia and they stopped several times to renumb everything.  There was some bleeding and a bit of bruising but nothing that felt inappropriate given the nature of the procedure.  I went home with an order for antibiotics and ketorolac.

My mouth hurt a lot Tuesday night and Wednesday but the pain didn’t feel disproportionate to the violence of the extraction.  I slept a lot and iced my jaw.  I could eat gingerly and talk.  Overall, I felt okay.  Not great, but okay.  I ironed work clothes on Wednesday night and got everything together to return to work on Thursday morning.

I woke up Thursday not because I had to work, but because of how badly my face hurt.  I had medicated before bed and it should not have worn off by that point.  I knew right away that something was wrong.  I flipped on the bathroom light to reveal flushed cheeks and glassy eyes, my hair matted to my forehead with sweat.  I put a thermometer into my mouth and started putting things into a backpack as the numbers climbed precipitously.  I had a fever of 103.2.  In less than an hour, I was in the emergency department of my regular hospital.

Dental procedures somehow manage to masquerade as routine despite the fact that they take a lot of skill to perform safely and that some of them are inherently risky.  Though the guidelines have been revised in recent years, many patients are still recommended to premedicate with antibiotics prior to dental work.  The reason is that it is very easy to transfer bacteria from the mouth to the bloodstream, even when all appropriate safety measures are followed.  If you have an artificial heart valve, or certain other conditions, there is an increased risk that these bacteria will become a true bloodstream infection, which is very, very serious.

The emergency department took me in right away.  I am always nervous in emergency departments because I have had a lot of trouble in the past, but everyone was great yesterday.  They knew about SM, they knew general guidelines and gave me no shit about needing hydromorphone for pain relief.  They were fine with following my home IV orders and using my port.  They worked together with my mast cell specialist, primary immunologist, dentist and PCP to make sure everyone was on the same page.

The big concern was that I had a bloodstream infection, or at least a bad dental infection, and that it would colonize my port.  My mouth looks fine and my white count is normal (which in itself is unusual, as it has been in the 16-20K range for years).  The port looks fine, isn’t red, tender or swollen, and works fine, which is great news.  All of this is good news except we have no idea why I have a fever of 103.

My doctors are generally fine with me handling things on my own at home, so I didn’t protest when they all said I should be admitted.  There is concern that because of some of my medications (like prednisone and Enbrel) that my bloodwork won’t show that I’m fighting an infection until it is severe.  So they admitted me to a surgical floor where I have been before and I’m just hanging out for a few days until we are convinced my blood cultures are truly negative.  The care has been excellent and there has been no bullshit about how I dose my meds, how often I use IV meds, or doing things the way I want them (dilute and slowly, as a rule).

I am on a stronger antibiotic as a precautionary measure, but I expect to have negative blood cultures and to go home in the next day or two.  The most plausible cause of this sudden high fever is that transient bacteremia, in which some bacteria from my mouth entered my bloodstream during the extraction.  My body then generated an immune response and was able to keep these few bacteria from becoming millions of bacteria in my bloodstream.  It’s basically a best case scenario.

I used to develop diagnostics for bloodstream infections.  I develop molecular diagnostics and have for several years, but my training is in microbiology and my focus was infectious diseases.   When I realized this tooth needed to come out, my biggest concern was that the tooth would get infected and I would get a bloodstream infection or that bacteria would be transferred during the extraction and I would get a bloodstream infection.  Most of the time, the most serious risk associated with a procedure I need is that I will have anaphylaxis.  This was different, and the way it played out proved that I was right to worry.

In the weeks leading up to getting this tooth removed, I talked to people in several dental/oral surgery offices, including the one where I was treated regularly for over fifteen years.  Some of the realized that I was not trying to be ridiculous and that there were rock solid reasons for me to want certain materials to be used, certain meds to be avoided and so on.  But, as there usually are, there were also several people who just thought I was being particular and difficult.  When people think this about me, they usually believe I have an anxiety disorder and that my need to control things is an extension of that.

And when they say to me, “You can’t control everything” with a snotty lilt on the last syllable, it’s not a bitchy imparting of a common adage.  It’s a warning.  For me, not being able to control everything could be catastrophic.  In some instances, it could be fatal.

The need to understand the entire procedure and know everything is not something I relish.  It is exhausting and scary.  Even when everything is done right – like my extraction on Tuesday – there are still risks.  There is still an unseen hand that can push us over the edge for no reason at all.

I have a short speech that I give to every single provider I meet who has not met me before.  It starts with, “Before we get started, I have a mast cell disease.  Have you ever treated anyone with that before?” I hit all the high notes briefly and tell them I will be using my Epipen first and then asking for help if I anaphylax, not the other way around.

Tonight I gave my speech to a new nurse.  We chatted about mast cell disease for a while.  “Does it bother you?  Having to teach everyone about this?”

It doesn’t, but if it did, it wouldn’t matter.  It’s my only chance to stay ahead of the unseen hand.

Death of the danger tooth

I finally got my tooth extracted yesterday. The root was really big so it took a couple of hours and a lot of force to get it out. My jaw is really sore but all in all, everything went fine.

I am giving myself a few more days to heal before I start going through my inbox/comments. I appreciate your patience.

The Danger Tooth

 

The Sex Series – Part Nine: Female pelvic floor dysfunction (2 of 2)

Muscular dysfunction in the pelvic floor starts when something happens that causes an injury or large scale inflammation to the pelvic floor.  This causes a large scale release of calcium, which causes the muscle to become too tight (hypertrophic).  As a result of this tightness, metabolism in the tissues increases and substances like histamine, serotonin and prostaglandins are released.  These mediators trigger neurologic pain perception.   The pain causes tightness, which causes more pain, and the cycle continues.

Hypertrophic muscles become musculodystrophic as fibrosis occurs.  The muscle becomes atrophied and is replaced by less extensible connective tissue.  As a result, the muscles aren’t as flexible as they should be. This also means that they cannot relax normally.  This activates trigger points in the pelvic floor and increases tone and spasm in pelvic structures, including the bladder, uterus, and rectum.

Treatment for pelvic floor dysfunction of women is very well described in literature.  It relies largely upon patient education and compliance with various exercises to retrain the muscles to relax completely at will.  Trigger-point pressure, both internal and external, can be applied by the patient or partner to help the muscles relax.  Vaginal or anal dilators, vaginal cones and bladder training can also be effective. Physical therapy including myofascial release and biofeedback are also important to treatment.

While initial treatment of PFD can be complex and time-consuming, the results are very good.  One study followed a cohort for ten years. 71% of women in this cohort reported major reduction or elimination of pain level following physical therapy and exercises done at home. After ten years, 89% of women reported major reduction or elimination of pain.  Many patients continued their home exercises during that time.

 

References:

Bortolami A, et al. Relationship between female pelvic floor dysfunction and sexual function: an observational study. J Sex Med 2015; 12: 1233-1241.

Hartmann D, Sarton J. Chronic pelvic floor dysfunction. Best Practice & Research Clinical Obstetrics and Gynaecology 2014, 28: 977-990.

Espuña-Pons M, et al. Pelvic floor symptoms and severity of pelvic organ prolapse in women seeking care for pelvic floor problems. European Journal of Obstetrics and Gynecology and Reproductive Biology 2014, 177: 141-145.

Ramalindam K, Monga A. Obesity and pelvic floor dysfunction. Best Practice and Research Clinical Obstetrics and Gynaecology 2015, 29: 541-547.

Graziottin A, et al. Mast cells in chronic inflammation, pelvic pain and depression in women. Gynecol Endocrinol 2014; 30 (7): 472-477.

Ahangari A. Prevalence of chronic pelvic pain among women: an updated review. Pain Physician 2014; 17: e141-147.