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Lisa Klimas

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

Epinephrine: Dosage and safety

How should epinephrine be used?

Epinephrine administered into the side of the thigh is the preferred route. 0.3mg (Epipen strength) – 0.5mg is recommended for adults. This can be repeated every 5-15 minutes as necessary. 16-35% of patients need a second dose of epinephrine to manage initial symptoms. Epipen Jr. contains 0.15mg epinephrine, which is usually recommended up to 66 lbs. Dosage for children is 0.01 mg/kg.

Aqueous epinephrine diluted 1:1000, 0.1-0.3ml in 10ml NS can be used intravenously over several minutes as needed. For potentially dying subjects, epinephrine diluted 1:1000, 0.1ml in 0.9ml of blood or normal saline (1:10000) intravenously. Give as necessary for response.

Aqueous epinephrine diluted 1:1000, 0.1-0.2mg, can be administered at reaction site (bee sting, etc.)

 

Statements on the use of epinephrine

Intramuscular adrenaline is the acknowledged first line therapy for anaphylaxis, in hospital and in the community, and should be given as soon as the condition is recognized. There are no absolute contraindications to administering adrenaline in children. Absolute indications for prescribing self-injectable adrenaline and prior cardiorespiratory reactions, exercise-induced anaphylaxis, idiopathic anaphylaxis and persistent asthma with food allergy. Relative indications include peanut or tree nut allergy, reactions to small quantities of a given food, food allergy in teenagers, and living far away from a medical facility.

Reference: Muraru A et al. Allergy 2007; 62:857-71.

 

Statement of the World Allergy Organization

The Committee strongly believes that epinephrine is current under-utilized and often dosed suboptimally to treat anaphylaxis, is under-prescribed for potential future self-administration, that most of the reasons proposed to withhold its clinical use are flawed, and that the therapeutic benefits of epinephrine exceed the risk when given in appropriate IM doses.

Reference: Kemp SF, Lockey RF, Simons FER, et al. Allergy 2008; 63:1061-1070.

 

Epinephrine may cause pharmacologic adverse effects such as anxiety, fear, restlessness, headache, dizziness, palpitations, pallor, tremor. Rarely, especially after overdose, it may lead to ventricular arrhythmias, angina, MI, pulmonary edema, sudden sharp increase in BP, intracranial hemorrhage. There is, however, no absolute contraindication to epinephrine use in anaphylaxis.

Reference: Simons FER. J Allergy Clinical Immunol 2004;113:837-44.

How to recognize anaphylaxis

When is it anaphylaxis?

Anaphylaxis is highly likely when any ONE of the three following criteria are met:

  1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (generalized hives, itching or flushing, swollen lips/tongue/uvula AND AT LEAST ONE OF THE FOLLOWING:
  • Respiratory compromise (difficulty breathing, wheezing, bronchospasm, stridor, reduced PEF, low oxygenation of the blood)
  • Reduced blood pressure or associated symptoms of end organ dysfunction (low blood pressure, collapse, fainting, incontinence)

 

  1. Two or more of the following that occur rapidly after exposure to a LIKELY allergen for that patient (minutes to several hours)
  • Involvement of skin, mucosal tissue (hives, itching, flushing, swollen lips, tongue, uvula)
  • Respiratory compromise (difficulty breathing, wheezing, bronchospasm, stridor, reduced PEF, low oxygenation of the blood)
  • Reduced blood pressure or associated symptoms of end organ dysfunction (low blood pressure, collapse, fainting, incontinence)
  • Persistent GI symptoms (crampy abdominal pain, vomiting)

 

  1. Reduced BP after exposure to KNOWN allergen for that patient (minutes to several hours)
  • Infants and children: low systolic blood pressure (age dependent) or greater than 30% decreased in systolic BP
  • Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline

Note: low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, less than (70 mm Hg + [2 x age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years.

“When a patient fulfills any of the three criteria of anaphylaxis outlined above, the patient should receive epinephrine immediately because epinephrine is the treatment of choice in anaphylaxis. There undoubtedly will be patients who present with symptoms not yet fulfilling the criteria of anaphylaxis yet in whom it would be appropriate to initiate therapy with epinephrine, such as a patient with a history of near-fatal anaphylaxis to peanut who ingested peanut and within minutes is experiencing urticaria and generalized flushing.”

Reference: Sampson HA et al. J Allergy Clin Immunol 2006; 117:391-7

 

How can I recognize anaphylaxis in someone else  (including children or non-verbal persons?)

Symptoms that can be recognized without self reporting:

Skin and mucus membranes: sudden onset hives, angioedema (swelling of the face, tongue, mouth and throat)

Respiratory: rapid onset of coughing, choking, stridor (high pitched breath sound), wheezing, difficulty breathing, cessation of breathing, turning blue

GI: sudden, profuse vomiting

Cardiovascular: weak pulse, irregular heartbeat, sweating, clamminess, paleness, fainting, loss of consciousness

Central nervous system: sudden unresponsiveness, low muscle tone, lethargy, seizures

Reference: Simons FER. J Allergy Clin Immunol 2007; 120: 537-40.

Treatment of anaphylaxis

Treatment of Anaphylaxis: ABC

Remember the mnemonic ABC.

A: Adrenalin (epinephrine)

Epinephrine is the recommended drug for treating anaphylaxis. It works by stimulating alpha- and beta-adrenergic receptors to inhibit mediator release by both mast cells and basophils. Use of epinephrine at onset of symptoms inhibits the release of PAF, which is largely response for the life-threatening manifestations of anaphylaxis.

B: Benadryl (diphenhydramine)

Antihistamines will NOT stop anaphylaxis. They help to manage the symptoms experienced subsequent to the reaction.

C: Corticosteroids (hydrocortisone, prednisone, etc)

Corticosteroids will NOT stop anaphylaxis. It can decrease risk of biphasic or protracted anaphylaxis.

 

Standard treatment for anaphylaxis

  • Epinephrine
  • Airway maintenance.
  • Oxygen, 6-8L/min.
  • IV hydration. 25-50 ml/kg of lactated Ringer’s solution or normal saline.

 

Treatment of anaphylaxis in mast cell patients

  • 0.3ml of 1:1000 diluted epinephrine, repeated 3x at five minute intervals if BP is less than 90 systolic (0.1ml for children under 12)
  • Diphenhydramine 25-50mg (12.5-25mg for children under 12) orally, intramuscularly or intravenously (slow push) every 2-4 hours; or hydroxyzine 25mg (12.5mg for children ages 2-12) orally every 2-4 hours
  • Methylprednisolone 120mg (40mg for children under twelve), intramuscularly or intravenously
  • 100% oxygen by mask or nasal cannula
  • Nebulized albuterol

Reference:

Emergency Room Response Plan. The Mastocytosis Society. Recommended by Dr. Mariana Castells.

 

Other treatment options

  • Diphenhydramine 50mg or more in divided doses, oral or IV. Maximum dose is reported as 300mg (5mg/kg) for kids and 400mg for adults (under supervision.)
  • Ranitidine 50mg in adults, 12.5-50 mg (1mg/kg for kids), administered by IV as 5% solution, total of 20ml, over five minutes.
  • Albuterol 2.5-5 mg nebulized in 3ml normal saline, or levalbuterol 0.63-1.25 mg nebulized in 3ml normal saline as needed.
  • Aminophylline, IV loading dose 5-6 mg/kg over 20 minutes, followed by IV infusion, 0.5-0.9 mg/kg/hr. Useful for persistent bronchospasm.
  • For persistently low blood pressure, consider dopamine 400mg in 500ml, intravenously at dose of 2-20 mcg/kg/min.
  • Glucagon 1-5mg (20-30mcg/kg, max of 1mg for kids) intravenously over five minutes, followed by IV infusion of 5-15 mcg/min.
  • Methylprednisolone 1-2 mg/kg/24 hours.
  • Sodium bicarbonate, 0.5-1 mEq/kg every five minutes as determined by arterial blood gases. Useful for persistent low blood pressure or acidemia.
  • Methoxamine 10mg has been reported as working following failure of epinephrine. Has been suggested as a next-line medication following failure of second dose of epinephrine; has not seen much use.

References:

Higgins DJ and P Gayatri. Methoxamine in the management of severe anaphylaxis. Anesthesia 1999: 54(11), 1126.

Neugut et al. Arch Int Med 2001

Yocum et al. J Allergy Clin Immunol 1999

Sampson H. N Engl J Med 2002

Sampson et al. J Allergy Clin Immunol 2006

Sheikh et al. BMJ 2006

Kemp SF and Lockey JACI 2002; 110:341-8

Biphasic anaphylaxis

Anaphylaxis has several described variants, including monophasic (one episode of symptoms), biphasic (a second episode after resolution of symptoms), late onset (occurring several hours after exposure to antigen) and protracted (in which symptoms took several hours to resolve despite treatment.) There have been multiple studies on the incidence of biphasic reactions which yielded differing results.

Stark and Sullivan described a 20% incidence of biphasic reactions in 25 patients. They found that patients experienced their second reaction 1-8 hours after the resolution of symptoms. Reactions were 2.8X more likely to be biphasic if the trigger was ingested or if the onset of symptoms was longer than 30 minutes after exposure. Laryngeal edema in the throat was also a risk factor. Severity of initial reaction or treatment administered did not correlate to whether or not the reaction was biphasic.

Douglas reported a 5.8% incidence rate of biphasic anaphylaxis. They found that higher doses of corticosteroids may have decreased the incidence of a second phase.

Lee and Greenes specifically investigated children. They found occurrence 1.3-28.4 hours after the resolution of initial symptoms. Most had wheezing and shortness of breath. Some had abdominal pain. Low blood pressure was rare. Importantly, they found that delay in administration of epinephrine was a predisposed patients to a second reaction. Patients who had only one reaction were administered epinephrine, on average, 48 minutes after exposure; those with two reactions, 190 minutes after. No other risk factors were identified.

18% of patients in the Brazil and MacNamara study were found to have biphasic anaphylaxis. Second phase occurred 4.5-29.5 hours later. They were unable to find clinical features that distinguished biphasic patients from uniphasic, but those with two phases did require more epinephrine to resolve initial symptoms.

Forest-Hay found that nine patients out of 91 had biphasic reactions. Eight of those had symptoms within six hours, a finding not seen in other studies.

A large study done by Smit on Hong Kong hospitals found a 5.3% incidence of biphasic reactions. They found that the time of treatment to onset of second phase averaged 7.6 hours. 12/15 biphasic patients had mild reactions. In particular, they found that biphasic reactors were less likely to have respiratory involvement (35% vs 77%.)

Ellis and Day found a 19.4% biphasic reaction rate. The second phase appeared 2-38 hours after the initial resolution. 40% of these patients had the second phase more than ten hours after the end of the first phase. The second phase could be milder than, similar to or more severe than the first. However, 40% had a lifethreatening second phase and 20% needed more treatment to resolve the second phase than the first. Biphasic patients had longer lasting initial reactions, were given less epinephrine and received less steroids. Late biphasic reactors (after 8 hours) took an average of 193 minutes to resolve their initial symptoms vs 112 minutes for uniphasic reactors. Importantly, no biphasic reaction was found in any patient who administered epinephrine and resolve symptoms within 30 minutes of onset. No biphasic if responded completed in less than 30 minutes. All patients received epi for treatment.

Delay in administration of epinephrine, inadequate dosing of epinephrine for first response, or need for large doses of epinephrine were found to suggest that biphasic anaphylaxis was more likely. Corticosteroid administration was not definitively found to prevent a second phase, but was generally considered to be beneficial. Previous cardiovascular history, older age, and use of beta blockers were risk factors for biphasic reactions. Oral ingestion of the trigger elevated the likelihood of a second stage, but it was also seen in parenteral and inhaled exposures. Hospital admission for 24 hours after resolution of symptoms is recommended.

Studies of mastocytosis patients have found that they are more likely to experience anaphylaxis, but true investigation of whether or not they are more likely to have biphasic reactions has been undertaken.

 

References:

Tole, John and Phil Lieberman. Biphasic Anaphylaxis: Review of Incidence, Clinical Predictors, and Observation Recommendations. Immunol Allergy Clin N Am 27 (2007) 309-326.

Douglas DM, Sukenick E, Andrade WP, et al. Biphasic systemic anaphylaxis: an inpatient and outpatient study. J Allergy Clin Immunol 1994; 93:977–85.

Lee JM, Greenes DS. Biphasic anaphylactic reactions in pediatrics. Pediatrics 2000;106: 762–6.

Ellis AK, Day JH. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients. Ann Allergy Asthma Immunol 2007; 98(1):64–9.

Brazil E, MacNamara AF. ‘‘Not so immediate’’ hypersensitivity: the danger of biphasic anaphylactic reactions. J Accid Emerg Med 1998 ;15: 252–3.

Forrest-Hay A, Taylor C, Tolchard S. Biphasic anaphylaxis in aUKemergency department. Presented at Open Paper Presentations of the 2003 Scientific Symposium of the Resuscitation Council of the United Kingdom (abstract)

Smit DV, Cameron PA, Rainer TH. Anaphylaxis presentations to an emergency department in Hong Kong: incidence and predictors of biphasic reactions. J Emerg Med 2005;28(4): 381–8.

Ablation

The summer of 2013 will probably always be remembered as one of the hardest of my life. It’s painful even to think about; bleak, with a few moments of light.

I could tell you a story about those months and all that pain, but the truth is that I don’t remember a lot of it clearly. When I think of that time, my mind conjures a memory of swimming at my best friend’s house. I climbed into the empty pool and swam to the side. I tucked my legs up against my chest, my feet planted firmly against the wall. I lay back, my hands atop one another, an arrow behind me. I pushed off, my head in the water, and slid cleanly through the water.

Above me, the sky was fairytale blue, the sun behind the dense green foliage of the tree overhead. The few clouds were gauzy, like set dressings. It really was such a beautiful day. There was a whole world before my eyes, but beneath the water, it was drowned out by the pounding of my heart. I closed my eyes and folded in on myself until the water enveloped me.

I find that the sicker I get, the less I want things. I am constantly throwing things away, donating things, evaluating what I really need. Last weekend, I opened a cardboard box with the ominous warning “Don’t open for six months” scrawled across the top. Inside, I found a book, notes, pictures of a dream I lost that summer. I flipped through them, looking through the corners of my eyes, before adding them to the garbage pile.

I’m not getting rid of things I don’t need. I’m getting rid of things that hurt too much to live with.

I live in a two room apartment. It’s small and utilitarian, but well decorated and softly lit. It has hidden places and a talent for finding depth where there should be none. Its limited space is a blessing; I cannot justify keeping these remnants of a personal history I have to turn away from. I clear my shelves of books on places I’ll never be healthy enough to go, donate my rock climbing gear and hiking boots, throw away clothes that will never fit over my swollen belly. After I take them out of my apartment and never have to see them again, I sleep well, swaddled in numbness.

This feels less spiritual and more primal. This is less self actualization and more self preservation. I am occupying a space and time where there is no room for thoughtful processing of my emotions. In this place, I am just cutting out everything that hurts.

I feel like I am surrounded by ephemera of all the things I’ll never get to be. Sometimes it’s all I can do not to tip my head back under the water and let myself be swallowed whole.

MCAS: Respiratory symptoms

Pharyngeal (throat) symptoms are quite common in MCAS and as usual, highly variable. Burning, painful, and irritated throats are frequently reported, and often automatically treated as viral infection or Strep throat, with no culture or negative culture. This pain can be chronic or intermittent. A chronic tickle in the throat or need to clear the throat is often present. Sinus congestion can lead to postnasal drip.

Sometimes MCAS reactions are localized to the throat, inhibiting ability to swallow or sometimes even breathe. This symptom is due to angioedema, and if breathing difficulty is observed, emergency treatment with epinephrine is required.

The most frequently noted lower respiratory symptom is a low level difficulty of breathing. This often presents as occasional wheezing, or feeling like you can’t get a deep breath. Patients rarely have severe wheezing, though it does sometimes happen. Chest x-ray and pulmonary function testing are usually normal.

Chronic non-productive cough affects a small portion of MCAS patients. They are often diagnosed with reactive airway disease for lack of a better explanation. Prostaglandin D2 is a potent bronchoconstrictor, approximately 10 times more potent than histamine, and is responsible in part for respiratory symptoms.

Mast cells have been implicated a variety of pulmonary pathologies, including COPD and pulmonary hypertension. Allergic asthma is not uncommon in MCAS patients and this population often reports successful treatment with Xolair.

References:

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

Anand P, et al. Mast cells: an expanding pathophysiological role from allergy to other disorders. Naunyn-Schiedeberg’s Arch. Pharmacol. 2012 May.

 

Dignity

I have always been socially awkward. For most of my life, there has seemed to be this set of universally applicable rules that I don’t understand. In particular, I find that I am generally neither embarrassed by not impressed with a variety of circumstances that seem extraordinary to the general population. I am not the kind of person who is upset by immodesty or esoteric ideas or the rending of social rules. I never have been. I don’t know why.

The day before my colostomy surgery, I was lying on my couch, trying to take a nap. My phone rang and it was a woman from an ostomy group. I remembered vaguely telling my ostomy nurse that it was okay to be contacted by this support group. I always say yes to stuff like that because I figure it can’t hurt.

The woman on the other end was very sweet. She asked if I was upset. I told her I wasn’t. She was gentle, but she persisted. She didn’t believe me.

“No, I really just want to be able to shit,” I told her, laying my arm over my eyes to block out the sun. “Honestly, I’m a lot more afraid of the damage from my mast cell disease if I don’t get this out than I am of shitting into a bag.” She was quiet for a while. “What?” I asked.

“Nothing, it’s just….You really aren’t upset,” she said finally.

“No, I’m really not,” I answered. And I wasn’t.

She offered me her many good tips on how to hide your ostomy bag. She clearly cared a lot (and felt badly – I was the youngest person her group had worked with) so I listened. She talked about girdles and pregnancy bands and tank tops and belt things with pouches and bathing suits. It was interesting, in a sort of voyeuristic way. I thought about her when I went swimming a couple of months later. My preparation consisted of putting on my normal two piece bathing suit and going in the pool. I didn’t see any reason to hide it. I wasn’t ashamed of it.

When I found out I was getting a PICC line, several people asked me how I would cover it. “With an occlusive dressing,” I answered automatically every time.

“No, like so people won’t be uncomfortable,” they sometimes followed up.

“It’s not my problem if they’re uncomfortable,” I said with increasing irritation every time I responded. “It’s not my fault I need the line.”

Someone asked me how I covered my port a few days after I got it. “I don’t.,” I said, thoroughly tired of this line of questioning. “It’s just not who I am.”

Modifying my body doesn’t upset me, even in the ways I just described. My hair has been in turns purple, blue, red, pink and red again. I had numerous piercings, all over my body, until once, after a surgery, when I just didn’t want to put the jewelry back in. It didn’t feel right anymore.

I am sure to many people, it must seem like my disease doesn’t upset me. That’s not the case. My relative resignation about the state of my illness is a survival mechanism. It looks a lot like not caring sometimes, but that’s not what it is. The pain shows, but it’s harder to see if you’re not watching carefully. It shows in the moments when I am unable to find even a shred of dignity.

Monday morning, I started anaphylaxing at work. I had a little bit of a cold and was overtired and sore and generally sort of walking the line anyway. I walked up to the nurse’s office and gave myself IV meds while she took my blood pressure. “It’s 88/60,” she told me with wide eyes. I didn’t want to epi at work because then they would have to call an ambulance. I knew the IV Benadryl and steroids would keep me stable for a bit so I called my mother. At the age of 30, I called my mother to come get me at work because I was too sick to get home safely. The nurse emailed my boss to tell him I went home sick, which was for some reason a lot more mortifying than it should have been. My father and cousin had to go pick up my car later. It was embarrassing.  It felt undignified.

Then, later on that night, my dog threw up. I completely lost it. I throw up most days, often multiple times. If it doesn’t all get into its intended receptacle, I just clean it up. No big deal. But these last few weeks have been grosser than usual as pertains to my GI tract and I am so sick of cleaning up shit. I couldn’t deal with it. I just hit a limit of grossness and indignity in my life sometimes and it’s like I can feel my self worth just leeching away from my soul into the air around me.  It’s a perception thing and it’s so individual.  I know how strange it is to some people that I don’t mind being transparent about my life, the external signs of my internal illness visible to the world, but sometimes am upset about needing help.  I know people think it’s strange.  But it’s not my problem, and it’s not my responsibility to behave in a way that makes people comfortable with my illness.

Someone posted this week about a “friend” who was upset that they joked about their illness. My response was something like, “That guy’s an asshat, it’s not your job to act how he thinks sick people should act.” And it’s not. I don’t keep my central lines uncovered because it makes some statement about illness. I keep them uncovered because I genuinely can’t be bothered. It’s just not who I am to care.

But I care about my disease, and I care about the life I can’t have because of it, and sometimes, it’s too much. Some days I am tired of cleaning up vomit and emptying bags of my own waste and cleaning blood stains out of my clothes. Do not mistake my resoluteness for apathy.

This ability to move forward, to not be upset about mundane things – it is a learned skill, not a natural acceptance of the terrible reality of chronic disease. We are just trying to find grace in life. We are just hoping to navigate through the rough pockets with some autonomy and a little bit of dignity.

 

Artifact

I have spent a lot of my professional life using microscopes. There is this rhythm you get into, when you do it a lot; lifting the edge of the slide out of the book with a gloved fingernail, pulling back the guard to slide the glass into place, spinning the fine adjustment back and forth with your fingertips. Sitting taller to look through the eyepiece into the tiny world below. Looking closely to see the ways you may have changed it.

The process of putting a sample on a slide and staining it can change it, sometimes even if you’re careful. Things look desiccated if you dry them too fast; elongated and distorted if you compress the sample. The dye sits heavy in some places and doesn’t wash off completely. When I look at a slide, I’m not looking at a sample. I’m looking at a sample that I changed in some way. These changes can be misread if not careful, because once I make them, they blend right into that tiny world. They are artifacts of my actions, some damage left behind by the process of being examined.

I spent most of last week in bed. My GI tract felt like I had swallowed lava. I had abdominal neuropathy that felt like electrical shocks spiderwebbing out from just below my xiphoid process. I was tired, weak and foggy from the anesthesia. I slept a lot and watched Netflix and did work from the relative comfort of my bed. These symptoms are not really so much from masto so much as they are from the procedure. Anytime I have a procedure, anytime I take medication, anytime I change my life to accommodate my disease. It leaves a lasting change not from the disease itself, but from the treatment of it.  It leaves an artifact.

I have had several surgeries. I have had hundreds of imaging tests. I have had so many scopes I literally don’t know how many scopes I have had. Every day I take handfuls of pills, infusions, injections, push meds.   This week I am acutely aware of the damage I have sustained by virtue of being treated for my disease. My mast cell medications bring my already slow GI tract to a dead halt. But of course the alternative is that I don’t treat my disease – and of course that’s worse. Right? It’s worse, right?

I know it is worse. I know that I will never live safely without meds. I in no way mean to imply that I am stopping treatment. It’s just getting really hard to know what is from my disease and what is from the treatment. It’s getting hard to know all the ways I have been altered by the experience of living with mast cell disease.

I feel more and more the toll this constant need for medical care is taking on me. With my accessed port, my surgical scars, my ostomy,  I myself am becoming increasingly damaged by this process. I am becoming an artifact.

Fragrance allergy

Public understanding of allergy pathology is often inaccurate and can create dangerous misunderstandings. The most common is that you must ingest a protein in order to have an anaphylactic reaction. Another is that inhalation or skin contact cannot cause severe reactions.

Both of these are inaccurate, especially, but not only, for people with mast cell disease. People without mast cell disease have severe reactions to IV contrast without having allergy antibodies to the protein (Singh, 2008). Inhalation can cause anaphylaxis. There are even cases of patients who can tolerate ingestion of a food but not inhalation, such as seen in Baker’s asthma, the second highest cause of occupational asthma in the UK (Ramirez, 2009). While ingestion of protein is the most common mechanism for severe allergic reactions, it is certainly not the only one.

Fragrance allergy is a growing problem worldwide. Fragrance is now one of the top five allergens in North American and European countries and can cause skin, eye and respiratory problems (Jansson, 2001). At least 100 chemicals commonly used in fragrances can cause contact allergies when applied to skin, even passively (Johansen, 2003). European Commission’s Scientific Committee on Cosmetic Products and Non-Food Products’ 1999 list of allergenic substances contained 24 chemicals and 2 botanical preparations, all used as scents (European Parliament and Council Directive 2003/15/EC, 2003).

Though the exact mechanism is not clear, perfume is known to cause asthma and other respiratory problems (Elberling J, 2009). A Dutch study found that isoeugenol, a common component of fragrances, can cause increased proliferation of cells in respiratory tract lymph nodes when inhaled (Ezendam J, 2007). However, more research is needed in this area.

A significant portion of the population also reports adverse reactions to scented products in general, even when worn by others. Products like scent lotions, perfumes, soaps and air fresheners are all cited as problematic. A 2009 paper reported on the results of two surveys of over 1000 people. 30.5% of the general population found scented products on other people to be irritating. 19% reported health effects from air fresheners, and 10.9% reported the venting of scented laundry products as causing symptoms. Percentages were higher among asthma patients and those with chemical sensitivity (Caress SM, 2009).

Symptoms reported from exposure to fragrances on others includes: headaches, chest tightness, wheezing, diarrhea, vomiting, mucosal irritation, reduced pulmonary function, asthma, asthmatic exacerbation, rhinitis, irritation of the airway, nose and mouth, and dermatitis (Caress SM, 2009).

Many of you are aware of the recent dispute over whether or not essential oils can be dangerous. They can. Even in the absence of known chemical triggers, the oils themselves can be triggering to many. As an example, clove oil, which has a large eugenol component, has been tied to severe allergic reactions (A.O. Nwaopara, 2008). Oils of citrus fruits are known to liberate histamine and make it more available to cause mast cell symptoms (Novak, 2007). Furthermore, while the reaction profile of each mast cell patient is unique, the hallmark of mast cell disease is anaphylactic reactions to seemingly harmless substances. Mast cell patients are increasingly being viewed as “canaries in the coal mine” for their ability to detect minute quantities of offensive components. While mastocytosis is rare, affecting about 0.3-13/100000 patients, some level of mast cell activation syndrome (MCAS) is thought to affect a much larger percentage of the population, in the neighborhood of 5% (Molderings, 2014).

Fragrances, from essential oil or otherwise, can cause contact allergies, headaches and respiratory symptoms. In mast cell patients, scents can cause severe full body reactions that are potentially life threatening or fatal.

MCAS: Pain

Pain is an unfortunate fact of life with MCAS. Muscle fatigue and weakness are common complaints, but myositis and rhabdomyolysis are rare. Some patients have elevated creatine kinase and/or aldolase, but have no related symptoms.

Bone pain is frequently reported with MCAS. Osteopenia and osteoporosis are common findings. Focal osteosclerosis is also sometimes found, but less frequently. Joints are often painful, which can lead to diagnoses of osteoarthritis, seronegative rheumatoid arthritis, fibromyalgia and polymyalgia rheumatica. Pain can migrate and is often poorly localized. Patients often feel pain in joints, bones and soft tissues, sometimes inconsistently.

Mast cells have been implicated in several pain disorders. Chronic lower back pain has been hypothesized to be related to mast cell activation for over a decade. Complex regional pain syndrome Type I, formerly known as reflex sympathetic dystrophy (RSD) and reflex neurovascular dystrophy (RND), is the most painful long term condition described. It is marked by neurogenic inflammation (nervous system swelling), sensitization of pain receptors and circulatory problems that cause swelling and color changes. It can affect any part of the body. Mast cells have been linked to the inflammatory response seen in CRPS patients.

Neurons with noradrenaline, serotonin and opioidergic receptors inhibit transmission of pain signals. (This is why taking opiates works for pain – it binds to these opioidergic receptors and suppresses the pain signals.) In the spinal cord, pain signals from the peripheral pathways meet up with the spinal pain signals to send to the brain. Here is where molecules like GABA, opioids made in the body and serotonin control pain transmission.

In chronic pain, serotonin acts to amplify the peripheral pain signals instead of suppress them. Increased serotonin levels and mast cell counts are found in many patients with chronic abdominal pain. About 95% of serotonin in the body is found in the peritoneal cavity, which explains the chronic pain many people feel in this region. Mediators released from colon biopsies in IBS patients were proven to excite the local nerves and activate pain receptors. Serotonin is one of these mediators.

Some antidepressants are known to affect serotonin secretion from mast cells. In particular, tricyclic antidepressants inhibit serotonin release in a dose dependent manner at higher concentrations. Clomipramine was seen to be the most effective, with amitriptyline and doxepin inhibiting release of serotonin and histamine at higher doses. All three were found to affect both uptake and reuptake of serotonin by mast cells and therefore lowering the relative concentration of serotonin in the local environment.

MCAS pain is often difficult to treat with typical pain medications. Antihistamines and cromolyn should be used to manage pain where possible. For bone related pain, bisphosphonates are usually effective. There is some data to suggest hydroxyurea can help manage pain in MCAS patients.

 

References:

Xinning Li, MD; Keith Kenter, MD; Ashley Newman, BS; Stephen O’Brien, MD, MBA. Allergy/ Hypersensitivity Reactions as a Predisposing Factor to Complex Regional Pain Syndrome I in Orthopedic Patients. Orthopedics 2014: Volume 37 · Issue 3: e286-e291

Giovanni Barbara, et al. Mast Cell-Dependent Excitation of Visceral-Nociceptive Sensory Neurons in Irritable Bowel Syndrome. Gastroenterology Volume 132, Issue 1, January 2007, Pages 26–37.

Ferjan, F. Erjavec . Changes in histamine and serotonin secretion from rat peritoneal mast cells caused by antidepressants. Inflammation Research 1996, Volume 45, Issue 3, pp 141-144.

Barbara, V. Stanghellini, R. De Giorgio et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology, vol. 126, no. 3, pp. 693–702, 2004.

Barbara, B. Wang, V. Stanghellini et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology, vol. 132, no. 1, pp. 26–37, 2007.

Afrin, Lawrence B. Diagnosis, presentation and management of mast cell activation syndrome. 2013. Mast cells.