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November 2014

Mast cells, heparin and bradykinin: The effects of mast cells on the kinin-kallikrein system

The kinin-kallikrein system is a hormonal system with effects on inflammation, blood pressure, coagulation and pain perception. This system is known to have a significant role on the cardiovascular system, including cardiac failure, ischemia and left ventricular hypertrophy. Despite significant research, it is not entirely understood.

Kininogens are proteins that have extra pieces on them. Kininogenases cut off those extra pieces. Active kinins that can act on the body are the result of this action. So kininogenases change kininogens to form kinins.

There are two types of kininogens: low molecular weight (smaller) and high molecular weight (larger.) We are going to focus on HMW, which circulates in the blood.

Also circulating in the blood are two other components called prekallikrein (sometimes called Fletcher factor) and Hageman factor (Factor XII.) When Hageman factor lands on a negatively charged surface, it changes shape and becomes Factor XIIa. Factor XIIa changes the prekallikrein to kallikrein. Kallikrein is a kininogenase.

When kallikrein finds a kininogen, it cuts off the extra piece to release bradykinin. Bradykinin is a kinin and is ready to act on the body.

Bradykinin has several functions in the body. It contributes to contractility of duodenum, ileum and cecum. In the lungs, it can cause chloride secretion and bronchoconstriction. It can cause smooth muscle contraction in the uterus, bladder and vas deferens. It contributes to rheumatoid arthritis, inflammation, pain sensation and hyperalgesia. It also induces cell proliferation, collagen synthesis, and release of nitric oxide, prostacyclin, TNF-a and interleukins. It can also cause release of glutamate by nerve cells. Glutamate has a variety of actions in the body and excessive release can cause epileptic seizures, ALS, lathyrism, autism and stroke.

Bradykinin acts on the endothelium, the cells that line the inner surface of blood and lymphatic vessels, to cause the blood vessels to dilate. This decreases blood pressure. It also regulates sodium excretion from the kidneys, which can further decrease blood pressure. Kininogen levels are reduced in hypertensive patients. Kinins, including bradykinin, oppose the action of angiotensin II, a hypertensive agent.

So how are mast cells related to this system? A couple of ways. The first way is that they release kininogenases and bradykinin. Tryptase can actually behave as a kininogenase. The second way is by being the exclusive producers of heparin.

As I mentioned above, Factor XII needs to change to Factor XIIa to initiate the formation of bradykinin. It does this when it contacts a negatively charged surface. In the lab, you can use a surface like glass for this. But in the body, it often happens on the surfaces of large, negatively charged proteins like heparin. (Side note: Factor XII is part of the clotting cascade. It can be activated by medical devices like PICC lines and that is why they carry a risk of clot formation.) So by releasing heparin, mast cells cause the formation of bradykinin. When the mast cells release heparin in inappropriate amounts, too much bradykinin is formed.

Overproduction of bradykinin is one of the principal causes of angioedema. In hereditary angioedema, the body is deficient in a component that regulates bradykinin. One of the reasons that physical trauma can cause mast cell degranulation is because it causes formation of bradykinin. Bradykinin in turn causes mast cell degranulation with release of histamine and serotonin, among other contents.

Bradykinin antagonists are being researched as possible therapies for hereditary angioedema. Icatibant is one such medication. Bromelain, found in the stems and leaves of pineapples, are known to suppress swelling caused by bradykinin. Aloe and polyphenols, like those in green tea, are also known to suppress bradykinin activity.


Kaplan AP, Ghebrehiwet B. The plasma bradykinin-forming pathways and its interrelationships with complement. Mol Immunol. 2010 Aug; 47(13):2161-9

Oschatz C, et al. Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity. 2011 Feb 25; 34(2):258-68.


Brunnée T, et al. Mast cell derived heparin activates the contact system: a link to kinin generation in allergic reactions. Clin Exp Allergy. 1997 Jun;27(6):653-63.



Lesser known mast cell mediators (Part 2)

Arylsulfatase A, also called cerebroside sulfatase, breaks down compounds to yield cerebrosides and sulfates. Cerebrosides can be either galactocerebrosides, which are found in all tissues of the nervous system; or glucocerebrosides, which are found in the skin, spleen, red blood cells and, to a lesser extent, tissues of the nervous system.

Arylsulfatase B, which has several other names, breaks down large sugar compounds, especially dermatan sulfate and chondroitin sulfate. Arylsulfatase B is mostly found in the liver, pancreas and kidneys.

Mutations in the gene for either arylsulfatase can lead to a variety of heritable disorders, including mucopolysaccharidosis VI and metachromatic leukodystrophy.

Chymases include mast cell protease 1, mast cell serine proteinase, skeletal muscle protease and so on. They are found almost exclusively in mast cells, but are present in small amounts in the granules of basophils. They have several functions, including generating an inflammatory response to parasites. They convert angiotension I to angiotensin II and therefore impact hypertension and atherosclerosis.

Bradykinin causes dilation of blood vessels, which induces a corresponding drop in blood pressure. It achieves its action by triggering release of prostacyclin, nitric oxide and endothelium derived hyperpolarizing factor. It also causes contraction of non-vascular smooth muscles in the respiratory and GI tracts, and is involved in the way the body senses pain. Bradykinin is important in angioedema.

Angiogenin, also called ribonuclease 5, stimulates the formation of new blood vessels. It drives the degradation of the basement membrane and local matrix so that endothelial cells can move toward the vascular spaces.

Leptin is the hormone that regulates hunger. It is mostly produced by fat cells, but is released by mast cells as well. When a specific amount of fat is stored in the body, leptin is secreted and tells the brain that it is full. It opposes the action of ghrelin, the hormone that tells your body it is hungry.

Renin, also called angiotensinogenase, is a critical component of the renin-angiotension system (RAS) that controls the volume of fluids not in cells, including blood plasma, lymph and interstitial fluid. It regulates the body’s mean arterial blood pressure. It converts angiotensinogen to angiotensin I.

Somatostatin, also growth hormone inhibiting hormone (GHIH), regulates the endocrine system, transmission of neurologic signals and cell growth by acting on somatostatin receptors and inhibiting the release of various secondary hormones. It inhibits secretion of glucagon and insulin. It is secreted throughout the GI system and decreases stomach acid production by downregulating the release of gastrin, secretin and histamine.

Lesser known mast cell mediators (Part 1)

I have posted at length about the roles of histamine and serotonin. Here are some less well known mast cell mediators. I will be doing in depth posts on the more relevant substances in the near future.

Monocyte chemotactic protein 1 (MCP-1), also known as chemokine ligand 2 (CCL2), draws other white blood cells, including memory T cells, monocytes and dendritic cells, to the site of injury or infection. It has important functions in neuroinflammation as seen in experimental autoimmune encephalitis, traumatic brain injuries, epilepsy and Alzheimer’s disease; and in diseases with pathologic infiltration of monocytes, like rheumatoid arthritis.

Chemokine ligand 3 (CCP7) recruits monocytes and regulates macrophage activity. It is known to interact with MMP2.

MMP2 (matrix metalloproteinase 2) is involved in tissue remodeling, reproduction and fetal development. It degrades type IV collagen. It has regulatory effects on the menstrual cycle and has been tied to growth of new blood vessels.

Interleukin 8 (IL-8), also known as neutrophil chemotactic factor (NCF), draws other white cells, mostly neutrophils, to a site of infection. It can activate multiple cells types, including mast cells, and promotes degranulation. It has been linked to bronchiolitis, psoriasis and inflammation.

MCP-4 (CCL13) attracts T lymphocytes, eosinophils, monocytes and basophils to an area of inflammation. Improper regulation can exacerbate asthma symptoms. Mast cells can release MCP-1 when stimulated by TNF-a and IL-1.

CCL5 (RANTES) attracts T cells, eosinophils and basophils. When IL-2 and interferon-γ are present, CCL5 activates natural killer cells and causes proliferation of the same. It is also important in bone metabolism.

CCL11 (eotaxin-1) specifically recruits eosinophils and is heavily involved in allergic inflammatory responses.

CPA3 (carboxypeptidase A3) digests proteins. It is released complexed with heparin proteoglycan along with chymase and tryptase.

Both interferon α (IFN- α) and interferon β (IFN-β) are made in response to viral infections. Their activities are regulated by IFN- γ. IFN- γ also draws white cells to the site of inflammation. Failure to properly regulate interferon levels can cause autoimmune disease. Interferons are so called because of their ability to “interfere” with viral infection. They are responsible for “flu type symptoms,” such as fever, muscle aches and lethargy.

All mediators listed here are produced by mast cells and stored in granules until degranulation.



For years I had a print of “The Lady of Shalott” above my bed. It is one of my favorite paintings. The story it tells is based on Lady Elaine, the Lily Maid of Astolat. She fell in love with Lancelot, who didn’t know of her feelings. When she realized he would never love her in return, she mourned for eleven days before dying of a broken heart.

After her death, her father placed her body in a boat and surrounded her with lilies. He sent the boat down the river, where the waterway would pass by Lancelot’s home. When the boat ran aground at the bend, people came out of the castle to see it. Only then did he realize what had happened.

Her story is about heartbreak and regret. But just as much, it is about expectations. Elaine fantasized about Lancelot so much and loved him so intensely that she expected that he had to know. He didn’t.  His ignorance destroyed her and he never even knew it.

I find the harder aspects of my illness come from expectations. I expect to wake up in a functioning body. I expect to not be in pain all day. I expect my brain to work at the speed it used to. I expect people to accommodate me. I expect to be treated fairly. I expect to be independent. I expect to live the life I want. I expect that someday, I won’t always be in pain and I won’t need dozens of medications and I won’t be afraid to eat something outside of my home.  I expect these things.  I want them so badly it seems like it could manifest through the sheer force of my will.

I would be disappointed a lot less if I didn’t have these expectations. But not having them feels like surrender.

I have always loved Elaine’s story. I never thought I would also deeply mourn the loss of something I never even had.

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


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.


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.



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.


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.


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.