Superhuman: An Update on Yzzy

Long time readers will remember the saga of Yssabelle, one of the little humans on my caseload. Two years ago today, Yzzy’s parents made the heart wrenching decision to move forward with the only remaining option: a bone marrow transplant.

For the uninitiated, Yzzy had true systemic mastocytosis, which is rare in a child. She also had a primary immunodeficiency, adrenal insufficiency, seizures and a half dozen other things. She reacted to everything. She couldn’t eat. She couldn’t go to school. She couldn’t run around. She had a central line and received continuous infusion 24 hours a day. She shocked multiple times a month. Just awful.

In 2016, after months of decompensating, Yzzy was diagnosed with hemophagocytic lymphohistiocytosis, a rare blood disorder that causes her body to eat up its own red blood cells. Mast cell patients around the world prayed for her, sent cards and presents, and bought the Girl Scout cookie she was shilling like a pro. We tried several therapies to manage the HLH. None of them worked.

There were a lot of things that we didn’t disclose at the time. People knew Yzzy was sick. Most have no idea how sick she was. Yzzy was dying. She was going downhill at a breakneck speed. She had failed other treatments for HLH. She had significant organ damage. The pain was awful. Without the transplant, Yzzy would die of HLH. But there was a less than 50% chance of surviving the brutal induction chemo and transplant. Truly the stuff of nightmares.

Because Yzzy was already assuming all the risk of a transplant, our goal became curing not just HLH but her systemic mastocytosis. While having no experience with mastocytosis, her transplant team was excellent. They were open to learning about mast cell disease and taking advice from experts. Ultimately, her induction chemo protocol was altered to increase our chances of success in killing two birds with one stone.

I don’t know a word strong enough to convey the terror I felt everyday for this little girl. Afraid to the point of paralysis. The stakes were so, so high. There was no margin for error.

I really thought she was going to die. I said to a close friend, “When Yzzy Eddlemon dies, I’m out.” Done with working patient cases. This wasn’t a moment of hysteria. I meant it. I didn’t think my heart could take watching another child suffer through everything that Yzzy had experienced.

But then something miraculous happened: she didn’t die. Against incredible odds (literally almost dying two days before the transplant), she survived. We anxiously waited for months to see if the transplant had cured her HLH and mast cell disease.

It did. It worked. Her mastocytosis and HLH were both cured. Her immunodeficiency and adrenal insufficiency and seizures all resolved. She could eat food. She wasn’t reacting constantly. There was no anaphylaxis.

She will be monitored for the rest of her life and some damage to her body was permanent. But compared to her life two years ago, a few appointments every six months is barely a blip on the radar.

Two years later, Yzzy is in third grade. She eats whatever she wants. She exercises as much as she wants. Laughing doesn’t cause reactions. She no longer has tubes running out of her body. She’s no longer on masto meds at all. She doesn’t have anaphylaxis.

Many mast cell patients have to cope with the fact that despite the seriousness of their disease, they often don’t look sick. Not so for Yzzy. Her illness was never invisible. She was covered in mast cell lesions and hives. She always wore a mask. Her alert dog was constantly by her side. Her lost her hair. She was sometimes so skinny she looked frail and at others was swollen to the point that she no longer looked like herself.

She has reached an important milestone in her life: she finally looks healthy. Her outside matches her inside. And because of this, I imagine that she looks ordinary. She’s not. She is the match that lit every candle extended toward her. A tiny vessel that held the hopes and dreams of thousands of people worldwide.

Healthy. Superhuman.

Wonder Woman.

Stability of compounded IV Benadryl

Hey,

I’ve been working on the IV Benadryl shortage from a different angle and I’m starting to see results. Currently, compounded IV Benadryl is considered a high risk sterile compound because it’s prepared from a non sterile solution (edit: I initially wrote non sterile solution here by mistake). Board of Pharmacy/FDA guidelines state that in the absence of other evidence on day supply, compounded IV Benadryl is good for three days in the refrigerator. They also state that freezing breaks the molecule, rendering it much less effective. I found data that demonstrates that both of these things are false. Compounded IV Benadryl CAN be frozen without affecting molecular stability. There’s also data demonstrating that compounded IV Benadryl is stable much longer than three days both at room temperature and refrigerated. This is without preservative. Just diphenhydramine and water.

Pharmacists can use this data to inform day supply at their discretion. If they decide to do this, patients can pick up large supplies with much less labor and cost to pharmacies.

I would urge patients who are unstable without this medication to contact a local sterile compounding pharmacy. In some places, large hospitals will sterile compound for established outpatients, but this is very location specific.

I know this is a scary and stressful time for many of us. I want to be clear that patients who require this medication are not at fault for its shortage. There are all kinds of process controls to prevent critical shortage of ubiquitous, life saving medications. Manufacturers, distributors, and pharmacies are ALL required to track usage to allow for increased production runs if needed. Hundreds of meds are used off label and production is increased when usage is properly reported. So if you’re barking up this tree, stop barking.

There are multiple factors contributing to the shortage, including shortage of FDA approved sterile diluents like saline; the fact that some manufacturers buy their IV Benadryl premade from another manufacturer and just relabel it; manufacturing sites closing for reasons including natural disaster and acquisition by other pharma groups; and communication issues from literally every agency and organization involved in the shortage and public notification. It is so, so complex. I would love to work with an investigative journalist to tell this story once the emergency is resolved. I do not release information I cannot prove and that is not the best use of my time right now. There will be a reckoning once people are safe.

Fresenius released a small lot of IV Benadryl on Monday. Most of this lot will be used to replenish institutions and emergency services providers before there is enough to distribute to patients. The fact that even a small amount is available is a good sign.

There is a rumor flying around that IV Benadryl is not going to be made anymore. I have worked in this industry for fifteen years, have contacts at the FDA and the CDC, and spent a lot of time talking to Global Program Management for this med for US licensed distributors. I have no reason to believe IV Benadryl won’t be made again. I believe that when the shortage resolves, patients will have ready access to this medication. If I learn anything that contradicts that, I will let people know.

This will end. We are getting through this. Okay? Okay. Courage.

xoxo,

Lisa

Link to data on stability of IV Benadryl

For patients affected by the IV Benadryl shortage

From the Mastocytosis Society:

URGENT Announcement about Diphenhydramine (benadryl) IV solution:

If you had been on IV diphenhydramine solution continuous infusion prior to the backorder, and are now seriously unstable because of it, please send an email to nurses@tmsforacure.org with the following information:

1. your name

2. the name of the physician who prescribes the

diphenhydramine and actually writes the order

3.your email address

4.your phone number

5.the name of your pharmacy and phone number or

infusion company if you would like it delivered there.

Please include a statement saying,”On November 6, 2018, I agree to let the TMS nurses share this information with pharmaceutical companies who make IV diphenhydramine.”

Please do not send in your name “just in case”. We have patients who are critically ill right now and need this medication.

Thank you.

Valerie M. Slee, RN, BSN, TMS Chair

Cataclysm

I have had a central line for four and a half years.  We placed a PICC line in early 2014 to facilitate vascular access in an emergency, to administer rescue meds at home during an anaphylactic event, and to allow me to use IV fluids at home to stabilize my blood pressure.

Shortly after I had my line placed, I was hospitalized for a five day long episode of protracted anaphylaxis. Because I had pretty much already tried every oral medication that could help manage my symptoms, trying IV medications was the obvious next step. I went home from the hospital with a prescription for IV Benadryl.

Speed matters a lot in management of mast cell disease. There is a tiny window of time during which immediate medication can stave off continued reaction or anaphylaxis. I learned how to dilute and push IV Benadryl during mast cell crisis.

Using IV meds was really nerve wracking at first, much more than I expected it to be. I’m an infectious diseases microbiologist by training and used to develop diagnostics for blood stream infections. I don’t think I can overstate how scared I was of getting sepsis. Every time I touched my line to flush or give meds, my hands shook and my heart pounded. But this was tempered by an obvious benefit: use of IV Benadryl as soon as a reaction started often prevented the need for epinephrine.

My health fluctuated over time. Eventually, I started using IV Benadryl as a baseline medication to manage daily reactions. It allowed me to exercise. It allowed me to eat. It allowed me to travel. It allowed me to work. IV Benadryl restored a much improved quality of life. I have used it ever since.

IV Benadryl is an old medication. It is off patent, cheap to produce, and made by multiple manufacturers licensed in the US. Overwhelmingly, it is used to manage anaphylaxis. Regular use as maintenance for patients was unheard of before the mast cell community began using it to manage reactions. Home use of IV Benadryl both for maintenance and for rescue – that is, to manage regular daily symptoms as well as to be lifesaving in the event of anaphylaxis – has become more popular in the mast cell community in recent years. I think I’m probably partly to blame for this – I have openly talked about how much it has helped me. I probably know a hundred mast cell patients who use it regularly.

In mid September, I got a call from my IV pharmacy. They were calling to tell me that vials of IV Benadryl were unable and they were going to dispense IV Benadryl in prefilled syringes. Fine. I didn’t care what package it was in. But I knew multiple organizations made this medication and I found it strange that vials from all of them would be unavailable at the same time. It was odd. But it was also true. Every manufacturer was reporting that it would be several weeks to months before the vials would be again be available.

A week later, my IV pharmacy called to let me know that the prefilled syringes were no longer available either. I found out on a Friday afternoon that come Tuesday, I would be out of medication. No one could get it. All distributors were out. I called over fifty pharmacies in Massachusetts trying to find some. I talked to the FDA. I talked to the manufacturers. I talked to hospitals nearby.

Despite being labeled a “critical backorder”, this phenomenon was something else entirely. It wasn’t “I can’t get enough of it.” It was “There is no IV Benadryl available anywhere in the US.” EMS is out. Hospitals are out. And every pharmacy everywhere is out or dangerously close. With only a few days warning, mast cell patients found themselves unable to get medication that literally kept them alive.

It is not overstating things to say that IV Benadryl is necessary to sustain life in a number of mast cell patients. I am one of them. Many people need it to maintain an airway. Others, like me, need it to recover blood pressure during anaphylactic shock. A lot of patients were only able to live outside of a hospital safely because they had access to this medication. The danger posed to these people is enormous. This is especially true because in an emergency, you can call 911 and have them take you to the hospital but they don’t even have the medication to treat you. This means that unless patients already have some, in a crisis, it is impossible to get more from literally anywhere. If you need this medication to survive, you are in real peril.

Compounding the issue is that IV Benadryl is the only potent H1 antihistamine available in IV form in the US. There are no alternatives for IV H1 antihistamines. It is IV Benadryl or IV nothing. It is also not used much outside of the US so getting it from abroad isn’t really an option.

Mast cell patients have been encouraged to use epinephrine as early as possible without IV Benadryl to potentially stave off a reaction. So we can all just use epipens anytime we react badly, right? Just kidding. Epipens are also on critical backorder. Okay, let’s use IV fluids to recover blood pressure during anaphylaxis and severe allergic symptoms. Haha, no. IV fluids are also on backorder. One of the safe narcotics for mast cell disease is no longer available. Certain benzodiazepines are no longer available. And we have no idea whether or not these medications will be available in the future.

The stress of this situation is paramount. I have patients getting trached to allow them to be hooked up to a ventilator. I have patients who can’t stand up without reacting or passing out. I have patients who are using epi multiple times a week. And I have patients who are scared to use their epipens so they gamble that they can control their reactions with something else. The single greatest risk factor for fatal anaphylaxis is delay in the administration of epinephrine. “Saving” epipens is dangerous.

Those of us who have won some stability through this medication are terrified of going back. I am terrified of going back. It’s already starting. After several months of debilitating symptoms and repeat anaphylaxis, I have been preparing to return to work in November. I love my job. I love my coworkers. I love my company. I can’t safely return to work until I have a guaranteed supply of IV Benadryl. And as of now, that could take months.

I am angry over this situation in a way that borders on holy fury. Mast cell disease is hard on its best day. It doesn’t need to be made even harder. Total loss of access to rescue meds is life threatening for many of us. In a country known for its premier healthcare, essential medications are completely unavailable. Mast cell patients were not even notified of an impending backorder to allow us to identify a source and stockpile. We were ignored entirely. This is the end result.

This is a dark time for our community. It is a time for fear and anxiety. It is a time of uncertainty. It won’t last forever. But that is cold comfort when you are terrified.

It is also a time to stand up and fight. It is a time to be visible. It is a time to be loud. It is a time to shame these organizations for letting this happen to us. Because if I have to suffer, I will damn well make them watch.

I know a lot of us are struggling. Be careful with yourself. Don’t take risks. Wait it out.

Take care of yourselves. Remember: it won’t always be like this. You don’t have to beat it. You just have to outlast it.

Bone manifestations of SM: Part Two

SM patients frequently experience bone pain, with one study finding 54% reporting it, with 18% reporting it as severe or intolerable. Another study (Barete 2010) of 75 mastocytosis patients found that 49% had bone involvement, 23% had osteoporosis (with 17% having vertebral fracture), 8% had osteosclerosis and 4% had a mixed pattern. When considering just ISM patients, 51% had osteoporosis with or without fracture. Fracture was more likely in older patients, male patients, and in patients with urinary n-methylhistamine levels above the normal cutoff (160 umol/mol creatinine.) A 2002 study on men with osteoporosis also found that men with osteoporosis and above normal n-methylhistamine levels were found to have bone marrow infiltration by mast cells.

One study (Guillaume 2013) looked at not only radiographic markers of bone abnormalities, but also at how serum markers associated with bone metabolism correlated to findings. In this study, bone mineral density was abnormal in 63% of patients, with 9/24 patients having osteoporosis and 15/24 having osteopenia. There was not found to be any relationship between the lesions seen or BMD alterations and age, sex, WHO mastocytosis type, tryptase level, serum parathyroid hormone level or serum 25-hydroxyvitamin D3 level.

However, levels of c-telopeptide, deoxypyridinoline and osteoprotegerin were highly associated with mastocytosis severity and tryptase level. C-telopeptides of type I collagen and deoxypyridinoline are markers of bone resorption, osteoprotegerin is a marker of osteoclast differentiation, and bone specific alkaline phosphatase is a marker of bone formation. Additionally, bone specific alkaline phosphatase was found to be correlate with tryptase level. In particular, higher levels of c-telopeptide and osteoprotegerin are associated advanced SM and high baseline tryptase levels. This study found that SM patients with c-telopeptide level above 2800 pmol/L had advanced disease 77% of the time; with deoxypyridinoline above 5.9 nmol/L had advanced disease 67% of the time; and osteoprotegerin above 5.5 pmol/L had advanced disease 67% of the time. Furthermore, all SM patients had higher levels of these markers when compared to healthy controls, regardless of WHO variant (SM vs ASM.)

A different study (Rossini 2011) found that bone turnover markers in serum did not correlate well with BMD or serum tryptase in ISM patients with osteoporosis. However, they were found to correlate well with bone turnover levels and serum tryptase in ISM patients with osteosclerosis. In particular, osteosclerosis was associated more with high baseline tryptase and high bone turnover markers. Osteosclerosis is more closely associated with aggressive forms of SM, including ASM and SM-AHNMD, and has been reported in 8-19% of patients with various forms of SM in multiple studies. Scattered sclerotic lesions have been noted in smoldering systemic mastocytosis (SSM) patients.

Previous studies had reported 3-8% of SM patients having an “osteopetrosis-like abnormality,” which has since been described as “skeletal disease caused by increased bone turnover.” The exact reason for this finding is unclear, but mast cells are known to stimulate osteoblast proliferation and activation. This increases production of osteoprotegerin, which in turn limits bone resorption.

In evaluating the WHO diagnostic criteria for mastocytosis, Escribano et al evaluated parameters found in ASM patients. 8/11 of them had C-findings that did not involve pathologic fracture. 7/8 of these patients had low LDH and increased B2 microglobulin, both of which are unusual in ISM. The other 3 patients met the criteria for ASM only because of their bone lesions. These patients first experienced pathologic fracture from lesions 18, 8 and 5 years after diagnosis with ASM, and 39, 34 and 15 years from SM diagnosis, respectively. All three patients had normal LDH and B2 microglobulin levels, with only 1/3 patients having progression of other disease parameters.

Bisphosphonate therapy is usually recommended for any SM patient with osteoporosis. It increases vertebral BMD and prevents osteoporotic fractures, but is less effective at increasing hip and femoral neck BMD. Dr. Pardanini recommends following guidelines for bisphosphonate use in multiple myeloma as a guide for use in SM. Interferon-a is the next line therapy for treating mastocytosis related bone pain and osteoporosis, particularly in patients who have new vertebral fractures despite bisphosphonate therapy. In severe cases, radiation therapy can help manage pain and bone loss.

 

References:

Rossini M, Zanotti R, Bonadonna P, et al. Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone. 2011;49(4):880-885.

Barete S, Assous N, de Gennes C, et al. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis. 2010; 69(10):1838-1841.

Biosse-Duplan M, Baroukh B, Dy M, de Vernejoul MC, Saffar JL. Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts. Am J Pathol. 2009;174(4):1426-1434.

Brumsen C, Papapoulos SE, Lentjes EG, Kluin PM, Hamdy NA. A potential role for the mast cell in the pathogenesis of idiopathic osteoporosis in men. Bone. 2002 Nov;31(5):556-61.

Nicolas Guillaume, et al. Bone Complications of Mastocytosis: A Link between Clinical and Biological Characteristics. The American Journal of Medicine, Vol 126, No 1, January 2013

Reinacher-Schick, S. Petrasch, B.J. Longley, C. Teschendorf, U. Graeven, W. Schmiegel. c-Kit mutation and osteopetrosis-like osteopathy in a patient with systemic mast cell disease. Ann Hematol, 77 (1998), pp. 131–134

van der Veer, W. van der Goot, J. G. R. de Monchy, H. C. Kluin-Nelemans, J. J. van Doormaal. High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 67 (2012) 431–438.

Peter Valent, Wolfgang R. Sperr and Cem Akin. How I treat patients with advanced systemic mastocytosis. December 23, 2010; Blood: 116 (26.)

Laura Sánchez-Muñoz, Ivan Alvarez-Twose, Andrés C García-Montero, Cristina Teodosio, María Jara-Acevedo, Carlos E Pedreira, Almudena Matito, Jose Mario T Morgado, Maria Luz Sánchez, Manuela Mollejo, David Gonzalez-de-Olano, Alberto Orfao and Luis Escribano. Evaluation of the WHO criteria for the classification of patients with mastocytosis. Modern Pathology (2011) 24, 1157–1168.

Pardinini, Animesh. How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage). April 18, 2013; Blood: 121 (16.)

Bone manifestations of SM: Part One

Osteoporosis is a progressive condition in which bone mass and density decreases. This leads to a greater risk of fracture, often fragility fractures, in which a bone breaks from normal activities like a small fall. These breaks usually affect the vertebrae, neck of the femur, wrist (Colles fracture) and ribs. Osteoporosis is defined as bone mineral density 2.5X less than the mean peak bone mass. Osteoporosis has no symptoms in and of itself.

Osteopenia is a decrease in bone mass. It is essentially pre-osteoporosis.

Osteosclerosis is an increase in bone density. This can occur when there has been damage to nearby bone and it has been crushed together into one smaller area.

Osteopetrosis is also an increase in bone density. It may lead to osteosclerosis. In osteopetrosis patients, it is due specifically to a rare genetic disorder.

Osteolysis is the active resorption of bone by osteoclasts. This means that the bone cells are essentially eating the bone away.

Osteoblasts are cells that make bone. Osteoclasts are cells that resorb bone. Your body usually resorbs bone and then puts new bone in the place it resorbed. This allows your body to repair bones.

Trabecular bone is found at the ends of long bones and in vertebrae. It is spongier kind of bone with more bone remodeling and turnover. These weaker places break more easily and are commonly affected in osteoporosis.

All of the conditions listed above are basically imbalances in the processes of bone resorption and formation. In osteopetrosis, the body is depositing bone more quickly than it is resorbing it. In osteosclerosis, more mineral is present in the bone than normal. This is usually caused by damage to the bone by trauma, osteoarthritis or other causes. Osteoporosis is usually the result of one of three mechanisms: excessive resorption of bone, deficient deposition of new bone when remodeling, or disuse, in which lack of mechanical stress on the bone causes bone loss (such as in people in bed rest.) Osteolysis is when your body actively and excessively resorbs the bone. It is a marker associated with severity in several blood disorders and cancers.

55% of Americans over the age of 50 have osteoporosis. 80% of those with osteoporosis are women. Osteoporosis can be caused by a variety of factors, including prolonged use of corticosteroids or several other medications, smoking tobacco, and post-menopausal estrogen deficiency. It is also found secondary to a large number of disorders, including mastocytosis.

Systemic mastocytosis patients who have one or more C findings are considered to have aggressive systemic mastocytosis (ASM), a more severe presentation with shorter expected lifespan. One of these C findings is “bone lesions with large sized osteolyses or/and severe osteoporosis with consecutive pathologic fractures.” Pathologic fractures are bone breaks caused by bone changes due to disease that caused weakness in the bone.

Due to the fact that osteoporosis is so common, there are a number of patients with ISM who have osteoporosis. It is only considered a C finding if it is severe, with multiple fractures due to bone damage, and cannot be attributable to any other cause. It is only a C finding if mastocytosis is the reason the bones are damaged to the point of repeat fractures. In particular, prominent mast cell physicians have spoken out against the inclusion of simple osteoporosis as a C finding, particularly because the risk can be modified with therapy and does not indicate poorer prognosis. Osteoporotic vertebral fractures are particularly prevalent in ISM patients. In one study, of 20% of SM patients with osteoporosis, 18.7% had affected spines compared to 2.5% with affected hip bones.

In SM, the presence of extra mast cells in the bone causes an increase in osteoclasts, which contributes to osteopenia and osteoporosis. Histamine, heparin, TNF, IL-1 and IL-6 are all mast cell mediators known to stimulate osteoclast action. In particular, histamine acts directly on osteoclasts and osteoclast precursors.

MCAS: Neurologic and psychiatric symptoms

The neuropsychiatric symptoms associated with MCAS are numerous and are results of the chemicals released by mast cells.

Headaches are a very common complaint. They can sometimes be managed with typical remedies (Excedrin, Tylenol) and antihistamine treatment often helps with this symptom quickly. However, in some patients, headaches can be disabling. Diagnosis of migraine is not unusual, with mast cell degranulation having been tied previously to migraines.

Dizziness, lightheadedness, weakness, vertigo, and the feeling of being about to faint are all typical in MCAS, though true fainting spells are less common than in mastocytosis. These symptoms often cause many MCAS patients to be diagnosed with dysautonomia or POTS.

MCAS patients often experience increased activation of sensory and motor nerves. This manifests as generic neurologic symptoms, sometimes several at once, like tingling, numbness, paresthesia and tics. Tics generally do not spread from the place they initially present. Paresthesias seem to progress for a period of time, then wane and disappear. Extremities are most commonly affected.

EMG and nerve conduction studies are typically normal or abnormal in a way that is not diagnostic. These tests sometimes reflect a possibility of chronic inflammatory demyelinating polyneuropathy (CIDP.) These patients also sometimes are positive for monoclonal gammopathy of unknown significance (MGUS), a blood marker that has been tied to multiple myeloma. However, in these patients, the MGUS is believed to be an effect of the MCAS.

Another subset of patients are diagnosed with subacute combined degeneration (SCD), a deterioration of the spinal cord associated with B12 deficiency. They are sometimes treated for pernicious anemia despite lack of hematologic support for this diagnosis.

Prostaglandin D2 is a known effector of nerve damage and has been blamed for many of the neurologic symptoms seen in MCAS. Astrogliosis, abnormal proliferation of astrocytes (nerve cells in the brain), and demyelination (loss of the insulating cover for nerves that allows the body to send signals) are markers of neurodegeneration. These factors cause scarring and inhibit nerve repair mechanisms. PGD2 is made by an enzyme called hematopoietic PGD synthase. In mice that don’t make this enzyme, these kinds of neuroinflammation are suppressed. Treatment of normal mice with an inhibitor of this enzyme (HQL-72) also decreases these actions. This indicates that PGD2 is critical in causing neuroinflammation including demyelination. PGD2 also activates pain receptors strongly, causing sometimes profound neurologic pain.

PGD2 is also the most potent somnagen known, meaning that it induces sleep more strongly than any other molecule. MCAS patients report inordinately deep sleep, “mast cell coma.” This is likely due to excessive PGD2. Conversely, some MCAS patients also have insomnia, from excessive histamine.

I have written at length before about cognitive and psychiatric manifestations of mastocytosis, which are the same as in MCAS. Cognitive and mood disturbances are all kinds are reported. Brain fog, including short term memory troubles and word finding problems, is the most common symptom. Irritability, anger, depression, bipolar affective disorder, ADD, anxiety, panic disorders and even sometimes frank psychosis can present. Such symptoms in mastocytosis patients were referred to as mixed organic brain syndrome, a term coined in 1986. The important aspect of these symptoms in MCAS is that they are caused by mast cell activation. As such, they are most effectively treated by managing mast cell release symptoms. Some patients do find relief in some psychiatric medications, but the psychiatrist should be aware that these symptoms are part of mast cell pathology.

Additionally, PTSD is not rare in MCAS patients. This is most often due to the trauma from negative interactions with the medical industry.

Autism is significantly increased in patients with mastocytosis. Similar findings are beginning to surface with MCAS patients. Interesting, most autism spectrum disorder patients have food intolerance and general allergic symptoms. A future post will discuss this in more detail.

References:

Afrin, Lawrence B. Presentation, diagnosis and management of mast cell activation syndrome. 2013. Mast cells.

Molderings GJ, Brettner S, Homann J, Afrin LB. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J. Hematol. Oncol.2011;4:10-17.

Ikuko Mohri, Masako Taniike, Hidetoshi Taniguchi, Takahisa Kanekiyo, Kosuke Aritake, Takashi Inui, Noriko Fukumoto, Naomi Eguchi, Atsuko Kushi, Hitoshi. Prostaglandin D2-Mediated Microglia/Astrocyte Interaction Enhances Astrogliosis and Demyelination in twitcher. The Journal of Neuroscience, April 19, 2006 • 26(16):4383– 4393.

Rogers MP, et al. Mixed organic brain syndrome as a manifestation of systemic mastocytosis. Psychosom Med. 1986 Jul-Aug;48(6):437-47.

 

Origins

I was born into a not really practicing Irish Catholic family. My grandmother is very religious. I went to CCD, had an Advent wreath and made the sacraments in time with all my peers. At no point was it ever explained to me who Jesus was or why I should love him. No one participating in my religious education ever had the vaguest interest in answering my questions about Jesus, Catholicism and the Bible. It pretty much just reinforced that it wasn’t something I would ever feel connected to.

When I growing up, my great aunt showed me how to read tarot cards. It was something several women in our family had done. She told me about crystals and herbs and our spiritual connection to the earth. She lent me books about the old Irish religion (Celtic paganism) and showed me how she incorporated some of these beliefs into her life. This felt real to me. This was the connection I had never had with Catholicism.

I grew into a teenager and read more about Paganism and met other people who believed in the same things. The major tenet of Paganism is to do no harm. It is one of the few world religions to accommodate the validity of multiple belief systems. Paganism does not purport to be the only true religion. It purports to be a religion that shares the world with other religions. It preaches good works and that the universe will punish or reward you according to your actions.

A very common misconception about Paganism is that it is Satanism, which it is not. There is no Satan in pagan religions. We do not sacrifice animals.  We do not eat children.  We are just regular people.

I had a really hurtful conversation today about Halloween. I explained the origins of Halloween from Samhain, the Irish end of the year festival. I explained that it had nothing to do with the devil. I was really not expecting the response that all gods other than the Christian God are guises of the devil, which implies that all of us who worship them are worshipping the devil.

Here’s the thing: I’m getting really tired of people judging me because I’m not Christian. I’m not Christian. I’m probably never going to be. Not everyone in the world is Christian. I am okay with not being Christian.

I have MANY close Christian friends. Many. I have no problem with their being Christian. They are respectful of my choice in religion. I participate in the important religious events of their lives. Sometimes we discuss the differences between our beliefs. We can agree to disagree. Neither of us feels superior to the other. Many of my friends post religious quotes or parables online and offer prayers when I am struggling. I have no problem with these things, and think prayer offers are kind and helpful. Crossfaith friendships are a thing. I have many.

This conversation in particular really upset me because of the events of this week. I stood out front of the entire mast cell community and wrote a public statement that has been read over 1000 times since first being posted. I answer hundreds of questions every week from everyone who asks me. I am actively putting together new initiatives to raise awareness and foster patient and provider education about our diseases. Two hours before this interaction, I was giving a presentation on mast cell disease to 40 researchers to spread awareness about our conditions. So when I’m doing all those things to improve the quality of our collective lives, it’s no big deal that I’m a devil worshipper? Just the rest of the time? Are you kidding me?

This post is not about Christianity. It’s about the fact that judgment is ugly and hurtful. I do not believe in helping a select group of people. I believe in offering the same help to everyone equally. But this is getting hard to live with. I shouldn’t be crying on my couch because someone who I help without question is judging me for my spiritual beliefs. And in the larger context of today, I have realized that this sort of thing is a lot more prevalent in my life than I was allowing myself to realize. My willingness to accept people just the way they are looks a lot like tolerance for this sort of thing and that’s my mistake.

I am a good person. I treat people fairly. I help people as much as I can, sometimes to the point of not getting enough sleep or talking to people in the ER in the middle of the night or reading obscure papers in bed with one eye open so I can find the answer someone needs. I am flawed, but I try hard to improve the lives of those around me. And I don’t judge people for their religious beliefs. Not even a little.

I accept your right to worship however you like and don’t make presumptions about the existential consequences of your religious choices. I am just looking for the same respect. You either accept me or you don’t. I am tired of overextending myself to help people who turn around and judge me in this way. It is unbelievably hurtful. I am not easily upset and I am not easily shaken, but this has got me questioning a lot of things.

I’m going to make myself scarce for a bit outside of my own MastAttack forum on Facebook (feel free to join if you haven’t) because frankly my recent experiences with social media are proving to be bad for my health. I feel like I haven’t written about the science of mast cell disease in ages so I’m going to return to doing that for a while.

As always, I’m here if you have questions. I just ask that you leave me alone if you think I’m a bad/ mislead/ confused person because I choose not to follow your faith. I think I deserve that much. No one needs to feel this way.

On emergencies and making a scene

I am a pretty brassy person.  (I’m sure this surprises people who don’t know me in real life, as I am so shy on the internet.)  I am not easily embarrassed and never have been.  I have always been klutzy and loud, and I figured out early on that it was easier to just not be embarrassed by that.  Self acceptance.  I has it.


However, there is one thing that I get very embarrassed about, and I’m sure I’m not alone.  That, my friends, is making a scene, particularly if that scene is health related. 
Let me give you an example.  A few weeks ago, I was sitting at my mother’s house after eating Eggs Benedict talking about an upcoming family event.  I wasn’t feeling great but I had received some bad news that morning so I figured it was from stress.  Suddenly my stomach started hurting badly.  It hurt as badly as a bowel obstruction, but I knew it came on too quickly to be one.  At that point, I realized I was starting to anaphylax.
But instead of giving myself epinephrine, I decided to see if it would just go away.  (I’m actually laughing out loud as I type this because of the sheer stupidity.)  Shockingly, it did not just go away.  After several minutes of wailing like a wounded animal from the abdominal pain, I got that killer “Irish girl spent all day on the beach with no sunblock” full body flush.  You know the one.  The one that says I’m anaphylaxing. 
At this point, I should have given myself epinephrine.  (Please note: I am not afraid of epinephrine.  It resolves my symptoms quickly and I know that nothing bad will come from using it.)  But I didn’t want to use my Epipen because I didn’t want to cause a scene.  This is so stupid.  I know this is stupid.  I know everyone reading this is shaking their head because it’s stupid.  But it’s true. 
So my mother and sister noticed me changing colors like a decoder ring and asked if they should call 911 and give me epi.  I said no.  Instead, I pounded liquid Benadryl.  I actually can’t drink things quickly in regular life (I was an embarrassment in college – there was no chugging of any type of alcoholic drink as I was just physically incapable), but when I’m taking Benadryl to try and avoid using epi, I am a champion. 
As I was open-throating Benadryl straight from the bottle, my blood pressure dropped precipitously and my field of vision got fuzzy like a dream sequence from 90’s television.  Then my heart did that really entertaining thing where it skips beats.  At that point, my sister called 911.
Now, let’s recap.  I understand my disease – check.  I know that I should use epi sooner rather than later when having anaphylaxis – check.  I am a medical scientist and understand on a molecular level that epi will not hurt me  – check.  I know that sometimes I have to go to the hospital because I have a life threatening disease – check.
So why didn’t I just epi and call 911?  Because I didn’t want to make a scene.
Literally, as soon as my sister called 911, I was embarrassed.  It’s stupid.  I know it’s stupid, but it’s true.  I know they didn’t care that I interrupted their day because I obviously needed medical attention, but it didn’t matter.  It’s not logical.  I don’t like needing emergency care, especially if I am with other people. 
The ambulance showed up and then like half the neighborhood suddenly needed to walk their dogs by my mother’s house at exactly the same time.  You know how sirens make dogs have to pee, right?  Right.  So now there are people outside with binoculars and I’m in (unattractive, ill fitting) pajamas at 11:30 while I explain my disease to the first responders who have never heard of it.  It shouldn’t be embarrassing, and I wouldn’t be embarrassed to be present if it happened to any of you, but it embarrasses me. 
Side note: I think I would actually be more likely to seek emergency care if I could be sure no one would find out.  This has nothing to do with the behaviors of the people in my life.  They are all wonderfully supportive.  I know.  I’m weird. 
I find needing emergency treatment of pretty much any kind embarrassing.  Emergency room, epipen, whatever.  Needing this type of medical attention inherently puts me out of control.   There’s always the chance that I’m going to end up admitted to the hospital and lose days of my life.  I know it’s sometimes necessary, but that doesn’t change how I feel.  I’m usually not interacting with providers who know me, so I can’t predict what will happen.  I don’t like that.  And I don’t like it when people see that, either.
I don’t like making people worry about me.  Until fairly recently, I kind of coasted with regards to public perception of my illness.  By this I mean that people knew I was sick, but didn’t know the severity, and I knew they thought it was less serious and I let them.  It was easier for me, and I don’t regret making that choice.  But it did mean that when I told people, a lot of them were shocked.  Like, really shocked.
I knew that once I told people, they would be upset because they care about me and they worry about me and want me to be fine. Embarrassing!  I don’t want them to worry, and I feel like any time I have to make a scene and call a lot of attention to my failing health, it just sort of reinforces the gravity of the whole situation. 

And then there’s this other part, where I worry that I’m making a scene unnecessarily.  Like I worry that I’ll call the ambulance and they’ll arrive and be like, “Oh, you’re fine!  Why did you call us?” even though I AM ANAPHYLAXING AND THERE IS A CHANCE I COULD DIE FROM LOW BLOOD PRESSURE.  Like I said, it’s not logical.

If any of you mast cell people told me you waited forever to give yourself epi, I would be all over you.  I would send you pretty infographics about how you should use epi early and quote statistics about how often people accidentally stick themselves with epipens and live to tell about it.  Because you should use epi early.  It will help you.  I know the party line AND I AGREE WITH IT but this fear of embarrassment thing is really strong.  And I am sure I’m not the only one who feels like this.

This may surprise you, but I’m actually much less afraid of medical professionals telling me I wasted their time than I am of people in my life telling me that.  I can handle medical professionals.  This is not my first rodeo.  But feeling like I disappointed the people around me sort of mentally reinforces that my disease is “wrong” and therefore I am “wrong.”   (Again – this feeling was not provoked by the actions of the people around me.)
So I’m trying really hard to get over this because if I’m being honest, I can’t really afford to be cavalier with this anymore.  I am anaphylaxing a lot more than I used to and my body  is tolerating it a lot more poorly than it has in the past. 
So, there you go.  I wrote an essay and called a lot of attention to my fear of having a lot of attention called to me when I need attention.