MCAD: General information for public

Mast Cell Activation Disorders (MCAD): Frequently Asked Questions

What are mast cell activation disorders?

They are a group of conditions  in which the mast cells in the body do not function correctly.  MCAD includes systemic mastocytosis, urticaria pigmentosa and mast cell activation syndrome, among other conditions. Mast cells are responsible for allergic responses. In MCAD, patients can have allergic type reactions to things they are not allergic to. These reactions can be very severe and even life threatening.

What are mast cell reactions?

These are reactions caused by mast cells being improperly activated. These reactions vary from person to person. Symptoms can include, but are not limited to, nausea, vomiting, hives, rashes, itching, flushing (turning red), dizziness, confusion and irritability. Symptoms are caused by the chemicals released by the mast cells.

What causes mast cell reactions?

Triggers vary from person to person. More common triggers include heat, cold, friction (especially on the skin), sunlight, foodstuffs, physical exertion, stress, dyes and fragrances. Triggers can also change over time, with new triggers presenting.

Are mast cell reactions dangerous?

YES. Many MCAD patients will experience uncomfortable reactions throughout their lives. However, every reaction carries the risk of anaphylaxis, a life threatening, severe allergic reaction. Therefore, avoiding reactions as much as possible is very important for mast cell patients. Each patient has an individualized response plan. For many, it involves removal of trigger and administration of medication, such as antihistamines or inhalers.

What is anaphylaxis?

Anaphylaxis is a severe allergic reaction affecting multiple organ systems in the body. These are the kinds of reactions observed in patients with bee sting allergies. Anaphylaxis can be fatal. It is a medical emergency requiring immediate treatment, usually epinephrine (Epipen.) Please receive guidance from treating physician on when to use an Epipen.

How are mast cell anaphylaxis and mast cell reactions different from normal allergies (like food allergies?)

With allergies, your body reacts by a specific method that involves ingesting and recognizing the allergen. In MCAD patients, the mast cells incorrectly think many things are allergens. Since mast cells are so sensitive in these people, ingestion of an allergen is NOT necessary to cause mast cell reactions or anaphylaxis. Smelling a perfume or breathing in very hot, humid air is enough to cause a reaction in many MCAD patients.

What causes MCAD?

Genetic mutations cause different kinds of MCAD. Recent studies have shown that mast cell disease can affect multiple members of the same family.

Why do some MCAD patients have spots?

These spots occur in locations where there are more mast cells than usual in the skin. These are NOT contagious rashes. In addition, MCAD patients who do not have permanent spots often have very sensitive skin, which may cause temporary marks or rashes.

How can I help an MCAD patient be safe?

By not being afraid of their disease. Respect their triggers and help them work around these limitations. Reactions can be painful and very scary, especially for kids. Learn the symptoms associated with reactions and be ready to help with a response plan.

 

Is there more information you feel should be included here?  Let me know in the comments and I can add it in.

Lost in space

One of my most deep seated irrational fears is being lost in outer space. Being lost, alone, surrounded by this vast expanse of loneliness – that is the fabric of my nightmares.

“If you die in space, your body just keeps moving until something hits it. Then the pieces keep moving. It doesn’t decompose,” I remember my middle school science teacher telling me. My revulsion was immediate and visceral. It seemed so unkind that space didn’t even offer this last kindness, the ability to disappear and be forgotten. You would be all alone, with no chance of help, and when you die, your body will memorialize this helplessness and despair, forever.

It feels hollow and soundless when I think about space – the ultimate loneliness. Sometimes when masto is too much and I am tired of living in a world that isn’t safe for me, I hide in bed with my feelings, and they are hollow and soundless, too.

A woman I sort of knew killed herself this morning. She had a young son with mastocytosis, and I knew her in the way I know many masto parents – I answered questions for her. I knew very little about her or her family or her own poor health. But her death has started a larger conversation about support that I think needs to be had, and I think we owe it to this woman to have it now. Because even if lack of support was not the reason she ended her life, it is definitely the reason many people in our community have contemplated doing the same.

Let’s pretend that you, my audience, are healthy. Let’s pretend you don’t have any chronic health issues. You’re walking down the sidewalk one day, listening to music on your Iphone and get hit by a car. You are taken by ambulance to the hospital and are relieved to find out that while your leg is broken, you are otherwise okay. Your leg needs some surgery and a cast and you will be good as new soon. You have your surgery and you go home.

Except what if eight doctors looked at your xray and told you your leg wasn’t broken but you could feel the bones shifting? What if you couldn’t bear weight on it, if your pain was excruciating, but they insisted you were fine? What then? What if you went home and stayed off your leg until you could figure out why it hurt only to be called lazy and lucky to be able to stay in bed all day? What if your spouse was upset that your leg hurt too much to move around the kitchen and cook dinner? What if your family members told your kids that your house was dirty because you were lazy and making up the pain in your leg? And what if you find a doctor who sees something on your xray and agrees to work with you, but your family tells people this was all your fault for going for a walk that day or listening to music or being outside? What if the people around you not only denied your condition, but actively refused to support you? What if they made you feel guilty not being unwell as if your sickness was your fault?

This is what life is like for a lot of mast cell patients. I hear from patients all the time that their spouse doesn’t believe they are really sick. I hear that their mother told their kids that they are lying. And for parents of sick kids, I often hear that one parent won’t acknowledge or learn about their kids’ disease. It is discouraging and horrifying and dangerous. Because just like ignoring a broken leg won’t make it heal, pretending someone doesn’t have mast cell disease won’t make them any less sick. It will just make them more alone.

I’m fed up with watching people I care about struggle with family members, friends, coworkers, etc, who feel that acknowledging and accommodating their disease is too much to ask for. I’m tired of my friends crying for support when they are alone in the ICU, going into shock in their home, because their family members won’t help them. This is abuse. No one deserves this.

To everyone who has a chronically ill person in their lives: If you are not helping, you are hurting. When you tell us we are faking or being dramatic or exaggerating, you are chiseling off little slivers of our being that we will never get back. You remind us that we are not worthy of help and sympathy in your eyes. You force us to stop asking for your support, until sometimes it becomes too much. Sometimes when you scream for so long and no one cares, suicide can seem like a relief.

I am very lucky to be well supported now, but I know the pain of begging someone to take care of you. It feels like a great dark expanse, weightless, silent and endless.

 

MCAS: Treatment

This post discusses medications used to treat MCAS. Doses listed are taken directly from “Presentation, diagnosis and management of mast cell activation syndrome” by Lawrence B. Afrin. These doses are general recommendations. Medication should always be taken under the direction of a provider who knows you and your case personally.

MCAS is generally treated identically to ISM, with the medications that block the action of released mediators, that prevent the release of mediators or that prevent the production of mediators. As a reminder, any medication that causes a reaction should be evaluated to see if it is truly caused by the drug or by a dye or inert ingredient. Medications compounded without dyes or noxious fillers can be truly life changing for mast cell patients. Generally, new medications for be trialed for 1-2 months to determine if they are effective.

Antihistamines are first line medications for both acute and chronic management of MCAS (but not for anaphylaxis – epinephrine is first line medication for anaphylaxis.) Most currently available antihistamines either block the histamine 1 (H1) receptor or the histamine 2 (H2) receptor and are referred to by the receptors they block. It is generally recommended for MCAS patients to take medication to block H1 and H2 receptors daily as baseline medications.

Loratadine is a common H1 starting medication. It has low anticholinergic activity and is not sedating. Dosing usually starts at 10mg daily and may be increased to 10mg 2-3 times a day. Fexofenadine starting dose in MCAS is usually 180mg every 12 hours; cetirizine 10mg every 12 hours; levocetirizine 5mg every 12 hours. Loratadine, fexofenadine and cetirizine are all available without prescription in the US. Of note, none of these medications are available for IV administration, so Benadryl should be used for emergency management of severe MCAS symptoms.

There are several H2 blockers available in the US, most over the counter. Cimetidine and ranitidine have more drug-drug interactions than famotidine and nizatadine. Famotidine, which is also readily sourced for IV administration, is usually dosed at 20-40mg every 12 hours, though in severe cases, doses of 80mg every 12 hours may be used. (This dosing is also seen in Zollinger-Ellison Syndrome patients.) Ranitidine starts at 75mg every 12 hours, increasing to 300mg every 12 hours. Nizatadine (Axid) is dosed at 150-300mg every 12 hours, and cimetidine at 400mg every 12 hours.

There are several other medications with H1 antihistamine effect. Tricyclic antidepressants, phenothiazine antiemetics (like promethazine) and quetiapine, an antipsychotic, are all H1 blockers. Addition of these medications often helps even when another H1 blocker is being taken by the patient. In particular, use of doxepin has been well described. It is usually started at 10mg twice daily and can be increased by 10mg twice daily to doses of 40-50mg twice daily. Beyond this, exhaustion and grogginess are often intolerable.

Ketotifen is a medication with both antihistamine and mast cell stabilizing properties, meaning it interferes with the release of mediators. The oral use of this medication for mast cell disease management is not well described, in part due to the oral formulation not being available in the US. Dosing is usually started at 1mg twice daily and increased in increments of 1mg twice daily until desired effects are noted and balanced with an acceptable side effect profile. As described by Afrin, single dosing is usually 6mg or less, and can be taken up to four times a day.

Benzodiazepines are often helpful in MCAS, due both to its action on mast cells and also directly on organs, particularly GI organs. Lorazepam, clonazepam and alprazolam are preferred due to their shorter window of action. All can be dosed beginning at 0.25mg every 12 hours, increasing by 0.25mg twice daily every week. Flunitrazepam has been described in treatment of mast cell disease. This medication has a longer halflife and is generally dosed at 0.5-2mg once a day.

Imidazopyridine medications like zolpidem (Ambien) also act on the benzodiazepine receptors of the body. Though usually taken for insomnia, some MCAS patients report relief of other symptoms. Whether or not these medications work in a patient seems independent of whether benzodiazepines are currently being taken by the patient or have worked or failed in the past.

Non-steroidal anti-inflammatory drugs (NSAIDS) can be helpful in MCAS patients who tolerate them. In particular, use of aspirin to bind prostaglandins has been very well described. A common starting dose is 325mg twice daily, with dosing up to 650-1300mg twice daily seen. Some patients take as much as 1300mg four times a day, but doses higher than 2600mg/day are unhelpful in most patients. Non enteric coated aspirin seems to be better tolerated and more effective at relieving symptoms in MCAS than enteric coated. In MCAS patients for whom aspirin is inappropriate (such as those with low platelets or decreased kidney function), COX2 inhibitors like Celebrex are sometimes used. Celebrex dosing in these patients usually begins at 100mg twice daily and increases up to 400mg twice daily.

Leukotriene inhibitors are frequently used in MCAS patients. Montelukast is the most common, being dosed as 10mg once to twice a day. Zafirlukast is dosed at 20mg twice daily. Doses should be decreased appropriately if liver dysfunction is also present.

Cromolyn is the most well known mast cell stabilizer, despite the fact that the mechanism by which it acts is still unclear. More recently, it has been noted to block mast cell receptor 35, which is increased when IgE is present. Cromolyn has extremely poor absorption, with 98% of oral doses being excreted unchanged. When inhaled, absorption increases to around 5%. Oral dosing is from 100-200mg 2-4 times daily. When nebulized, dosing is usually 20mg 2-4 times daily. Of note, patients usually experience a resurgence of symptoms when first starting the medication that may last 3-4 days. In my experience, this symptom increase is sometimes observed when increasing the dose. It can take several weeks to determine if cromolyn is truly effective in patient, with some people only seeing serious gains after four months.

Pentosan is less well known mast cell stabilizer whose mechanism is likewise unknown. This medication is commonly used in interstitial cystitis, a mast cell disorder that affects the genitourinary tract. Though Pentosan seems to be most effective in the GU tract, some patients report decrease in other symptoms while on this medication. It is usually dosed at 100mg every 8-12 hours.

Quercetin is commonly mentioned as a natural/homeopathic mast cell stabilizer. After much research on the topic, I have to say that I agree. It has been found to inhibit lipoxygenase and cyclooxygenase, which in turn decreases production of leukotrienes and histamine. It is usually dosed starting at 500-2000mg per day, divided up into 2-4 doses. For example, a daily dose of 500mg may be taken as 125mg four times a day. A newer form, quercetin chalcone, is usually taken at 250mg three times a day.

Pancreatic enzymes, like Creon, are sometimes helpful in MCAS patients who have pancreatitis symptoms, even if they are not having pancreatic type pain. It sometimes helps with chronic diarrhea, weight loss and malabsorption.

Corticosteroids like prednisone are sometimes used to manage MCAS symptoms.  These medications can prevent mast cells from producing mediators and as such can be very effective.  However, long term use can have severe side effects and as such is discouraged.

Omaluzimab (Xolair) is an anti-IgE antibody. It is not clear exactly how this stabilizes mast cells reacting by a non-IgE mechanism. Xolair is injected subcutaneously at doses of 150-300mg every 2-4 weeks. It should be trialed for at least 3-4 months before determining if it is effective. Interestingly, whether or not a patient responds and how well seems to be independent of their pretreatment IgE level.

The successful use of chemo medications for severe MCAS cases has been described in literature. In particular, hydroxyurea can be effective, though rapid onset and severe low blood cell counts are a real risk. It is usually started at 500mg daily and increased up to 2000mg daily as needed. Blood counts should be monitored weekly for four weeks at the onset of treatment and after any dosage increase. Tyrosine kinase inhibitors, like imatinib and dasatinib, have also been used as last resorts in MCAS patients. Imatinib is usually dosed at 100-200mg daily and dasatinib at 20-50mg daily. Patients on these medications require careful monitoring for pulmonary and renal issues. All chemo patients are at increased risk of infection.

IV hydration is being used more frequently to manage baseline symptoms of MCAS patients. TNF-alpha inhibitors have been suggested to help mast cell symptoms, but there have been no symptoms. (I take a TNF-alpha inhibitor for autoimmune issues and do find it helps to relieve some of my mast cell symptoms.) Other possible avenues include IL-1 and IL-1b inhibitors and kinin-b2 receptor blockers. Tryptase inhibitors continue to be in development.

 

Reference:

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

 

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.

Sorry not sorry – Why I’m calling out singer Natalie Grant

Saturday afternoon, a masto friend reached out to me.  She was upset about a Facebook post by a prominent Christian singer, Natalie Grant.  Ms. Grant posted the following to her Facebook wall on Saturday:
“Such a sweet time in Minneapolis at Women of Faith.  But now it’s on to LAX to continue filming the next episode of It Takes a Church.  And why yes, that is a battery operated essential oil diffuser that I’m using in my airplane seat.  Rocking the thieves oil and keeping the germs away.  And it’s helping the plane to smell much better #sorrynotsorry”
I groaned when I read it.  I actually groaned out loud.  I opened the thread to find mast cell patients commenting that oil diffusers can be dangerous for people like us, that they could trigger anaphylaxis. Grant’s fans argued that these people were just looking for something to complain about, that oils could never harm anyone, that you have to ingest a protein to have anaphylaxis.  The general spirit of their responses was that mast cell patients were just being oversensitive. 
That’s exactly right – but not the way that they mean.  Our bodies experience severe reactions to pretty much anything – and those reactions aren’t in our heads.  The fact that so many people commented that it was impossible for an oil diffuser to present a real health risk to others represents a serious danger to people like myself.  That is why the mast cell community found this so upsetting.
So let’s discuss why this is dangerous for people with mast cell disease.
Mast cell diseases are a group of disorders in which your body either makes too many mast cells, mast cells do not function correctly, or both.  Mast cells are the cells that are responsible for allergic reactions.  For normal people to have an allergic reaction, their body has to make a molecule called IgE that remembers it is allergic to something.  So people with peanut allergies have peanut IgE, and when they eat peanuts, the peanut IgE tells the mast cells to have an allergic reaction. 
People with mast cell disease pretty much skip this step entirely.  We have severe allergic reactions to things we are not actually allergic to.  This includes lots of foods, materials, environmental factors and others.  For some people with mast cell disease, these reactions include unpleasant symptoms that can be managed at home, like nausea/vomiting, skin reactions, headaches.  But some of us have severe, life threatening anaphylactic reactions based upon even very casual exposure to these substances.  These reactions require use of epinephrine (Epipens), IV antihistamines and steroids, and monitoring at the hospital to ensure that we survive.  People with severe mast cell disease can have several of these episodes in a year.  (I had three in 48 hours in May.)
To be clear: anaphylaxis can be fatal.  Mast cell patients are more likely to experience anaphylaxis and more likely to have severe reactions.  Our best protection is to avoid triggers and medicate appropriately, but this isn’t always possible.  Due to the rare and unusual nature of our diseases, there are few specialists worldwide so the vast majority of patients must fly to see them.  Hiding at home all the time with a mask on is both not practical and not an acceptable way to live. 
Every day, people with mast cell disease seek to minimize the damage to their bodies by avoiding triggers as much as possible.  In enclosed indoor spaces, this can be particularly difficult.  Once triggered, the only option is to medicate and end exposure to the trigger.  When flying, this is obviously impossible. 
While mast cell diseases are rare, fragrance sensitivities and asthma are not.  The CDC has stated that some risks of exposure to scents include asthma attacks, allergic reactions, headaches, migraines, sore throats, coughing, eye irritation, and other medical symptoms.  Asthma attacks can be triggered by fragrances in 72% of asthma patients.  Patients with multiple chemical sensitivity often have severe symptoms similar to those mast cell patients experience.  The fact that workplaces are gradually transitioning to be fragrance free environments is indicative of scent exposures negatively impacting the quality of life for many people. 
In an age of increasing allergies and allergic-type reactions, I find that people like me are often at odds with people who feel their personal liberties should not be curtailed.  Many people see this stand against the use of a personal diffuser as an attempt to impose the will of a suffering minority onto the population at large.  They are entitled to feel however they feel.  But as a mast cell patient, this is about allowing us to move as safely through the world as possible.  Is it worth feeling “infringed upon” to not use an oil diffuser in an airplane when it could kill someone?  Literally kill them?
Natalie Grant put up a follow up to the original post the next day.  While it initially looked promising, I was very disappointed.  It includes such gems as, “I am not here to argue about whether pure Young Living essential oils specifically, can harm those with this disease.” And, “I have a niece that is so allergic to peanuts, she can be in the front row of a plane and the person in the back row can open a bag of peanuts and she can go in to anaphylaxis.  However, EVERY TIME she flies, she has to inform the airline and flight attendents of her life-threatening condition.  May I make a suggestion to those who are suffering: be vigilant with airline employees.  DO not allow the plan to take off until the passengers have been informed there is someone on board who has a specific life threatening disease, so please do not use perfumes, lotions, oils, etc while on board the plane today.  No one will be a better advocate than YOU.”
This statement sums up exactly how much Natalie Grant is missing the point.  If I stood up in front of a plane and told people not to use anything scented, they would snicker and still use them because nobody believes we can actually die from a reaction to a scent.  When mast cell patients spoke up to point out that her use of an oil diffuser could be dangerous to us, we were mocked and shouted down.  We are advocating for ourselves.  The problem is that Natalie Grant, and her fans, just aren’t listening. 
And mast cell disease being dismissed publicly by someone with her sphere of influence?  Well, I’d venture my world is even a little bit more dangerous now than it was before Saturday.  So I’m calling her out.  #sorrynotsorry
A succinct presentation that sums up scent related health issues for the general public (along with list of references for above statistics) can be found here: http://www.slideshare.net/J_A_Miller/fragrance-sensitivity-awareness

How to get out of a reaction cycle

If you have mast cell disease, your basic arsenal for managing your disease should include elimination of/ avoidance of known triggers, low histamine diet, second generation H1 antihistamines and H2 antihistamines.  Leukotriene inhibitors, aspirin, mast cell stabilizers, steroids and anti-IgE are also possibilities for maintaining a baseline.
As a mast cell patient, a decent baseline is what you are going for.  A reasonable baseline does not always mean that you can live the same way you did before your diagnosis.  It means that you are somewhat functional on a day to day basis.  What this looks for is different for everyone, but I aim for not being in bed for 20 hours a day, not being in 5/10 pain every day, being mentally coherent.  Most importantly, you should not have to take rescue meds frequently.  If you need rescue meds often, then you are not covering your mast cells well enough with your regular meds.  If you have eliminated triggers, then this usually involves tweaking your meds. 
I’m going to give you my insights on what that looks like, but please keep in mind that any med changes should be discussed with your treating physician.  We are all different people and med dosing can be affected by many factors. 
Part of why mast cell patients are prescribed second generation H1 antihistamines is because they are usually not sedating, have little anticholinergic activity and are, to be honest, pretty safe.  Mast cell patients often take several times the recommended daily dose on medications like loratadine and cetirizine.  (Please note: the daily recommended dose for Benadryl, which is a first generation H1, should be respected – overdosing can have serious consequences.)  So while the average person may take one Zyrtec a day for allergies, a mast cell patient may take 3 or 4 a day.  The same is true for the H2 antihistamines, like ranitidine and famotidine.  It’s not unusual to dose very high on those. 
If you have uncontrolled symptoms on second generation H1 and H2, changing the meds to something else in the same class may help.  Sometimes Pepcid works better than Zantac, or whatever.  Some people find that using one Allegra and one Zyrtec works better than two Allegras.  Consider also that inactive ingredients can be triggering and thus decreasing the effectiveness of a med.
If you have screwed around with H1 and H2 meds and have increased doses, adding leukotriene inhibitors, cromolyn or atypical H1 meds, like promethazine or doxepin, may help.  If that fails, ketotifen helps a lot of people, and anti-IgE (Xolair) has benefited some mast cell patients.  Beyond this, you are looking at things like regular IV fluids, steroids, and less palatable choices.
As I mentioned before, having a good baseline means not using rescue meds regularly.  This is really important to feeling as well as possible.  Serious reactions take a while to recover from, even if they don’t need epi.  So if you’re having one every day, it is impossible to get to your baseline without serious intervention.  The meds used to control serious reactions, including Benadryl, can cause rebound reactions that look like anaphylaxis, but are not anaphylaxis.  Let’s talk about this.
Benadryl can cause rebound reactions for two primary reasons.  The first is because it is a very strong antihistamine and it stops histamine release symptoms really well.  One of the things Benadryl does is it stops mast cells from releasing histamine.  So when it wears off, mast cells tend to release a lot of that histamine at once.  Another release is that Benadryl has very strong anticholinergic action.  When your dose wears off, you can have what’s called “cholinergic rebound.”  This can cause headache, nausea, vomiting, diarrhea, brain fog and other symptoms.  Sound familiar?  This is why people feel “hung over” when their Benadryl wears off.  Second generation H1 antihistamines, like cetirizine and fexofenadine, have almost no appreciable anticholinergic activity so they tend to not have this side effect.
Mast cell patients get hit with the double whammy of sizeable histamine release at the same time as they get hit with cholinergic rebound.  So rebound reactions can feel like anaphylaxis, but they’re not the same thing.  If you take Benadryl every day, you are going to have a rebound reaction every day.  It may not be severe, but this is not uncommonly the culprit in patients who say they always get sick around the same time every day. 
Another reason why it is generally not recommended for mast cell patients to take Benadryl every day is because it can stop working.  This is called tachyphylaxis and it basically means your body gets used to it.  When you need to use epinephrine, you are counting on Benadryl and steroids to help control the effects of anaphylaxis on your body.  Patients in whom Benadryl is ineffective get into very dangerous situations when they anaphylax.  I have a few friends like this and it is seriously not pretty. 
It is possible for anaphylaxis to be biphasic or protracted.  Biphasic reactions are not common, but seem to be more common in mast cell patients than the general population.  (This is my personal observation.)  In these reactions, once the reaction is stopped with epi, you can have another anaphylactic episode of the same or worse intensity without a trigger.  This generally happens within 24 hours and is the original reason Epipens were sold in pairs.  In protracted (sometimes called multiphasic) reactions, this can continue to happen for a number of days.  I find in my personal experience that use of epi early is the best way to avoid multiphasic reactions. 
If you absolutely must take a medication that causes a serious reaction (by which I mean not a typical side effect), desensitization is usually recommended for mast cell patients as opposed to taking antihistamines with each dose.  This method really just suppresses the immediate symptoms, not the inflammatory response.  Drug reactions for mast cell patients can be serious and any reaction can escalate even when it has been mild in the past.  For patients who react to salicylates, but need to take aspirin, Dr. Castells has written an aspirin desensitization protocol that is frequently used.
Part of why people get into these cycles with rescue meds is that they often don’t understand why they are having reactions.  Mast cell patients need to keep careful inventory of their daily histamine level because things that may not cause reactions individually can cause a reaction when you have them all together.  For example, if you have a relaxing day with no stress, maybe you can eat a spinach salad.  But if you go for a walk outside in the heat, and you eat that same spinach salad, you may have a reaction.  This doesn’t just happen to mast cell patients – there are plenty of recorded instances of patients having allergic reactions to food ONLY IF THEY EXERCISED THAT SAME DAY.  This is because exercise increases histamine.  Heat increases histamine.  Eating increases histamine. Stress increases histamine.  Sex increases histamine.  So all of this histamine adds up.  So you may be able to drink a beer, or you may be able to walk two miles, but if you try to do both the same day, you may have a reaction. 
Of course, there is also an idiopathic aspect to mast cell reactions, which means that some people have symptoms for truly unexplained reasons.  However, I find these happen a whole lot less when you really track activities/histamine and try to eliminate triggers. 
Part of how I evaluate my “histamine baseline” for any particular day is by certain physical parameters that I refer to as my “mast cell dead giveaways.”  If these are present, I know I am already starting out as reactive and need to lay low and avoid histamine that day.  Allergic shiners, which look like black eyes, or dark circles under the eyes, are one for me.  Swelling in my fingers tells me I’m having some edema from mast cell degranulation.  The taste of metal in my mouth often precedes reactions.  Skin being more reactive than usual is a very clear indicator for me.  On a reactive day, squeezing my arm with my hand will make my entire arm turn red.  I take my blood pressure in the morning and if my whole arm is red or has hives when I take off the cuff, it is a clear sign to me to not take risks that day.  Any type of “cold symptoms” (cough, stuffiness, clearing of the throat, sore throat) and I have to assume infection, which contributes to mast cell activation and thus to your histamine quota. 
I have written before about how to manage mast cell reactions with medication, so please refer to that post for more details.
Keep track of your histamine inventory.  Learn the “dead giveaways” for your body so you can self check.  If you’re taking Benadryl every day for symptoms, it can often be resolved with increasing meds/ adding other meds.  Taking Benadryl every day should be avoided, especially because it causes rebound reactions that can mimic anaphylaxis symptoms.