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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.

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 2

The term orthostasis means to stand up. Orthostatic intolerance is the presentation of symptoms which interfere with or prevent standing up. Orthostatic intolerance (OI) affects heart rate, blood pressure and blood distribution in the brain. This can present as a number of symptoms with multiple root causes.

The autonomic nervous system is responsible for making quick changes to the cardiovascular system based upon changes in the environment. It adjusts the circulatory system by changing heart rate, constricting blood vessels and inducing secretion from the adrenal gland to sustain a normal blood pressure.

The sympathetic nervous system is one part of the autonomic nervous system and its function is to activate the fight-or-flight response. When it malfunctions as in OI, it causes pallor, headache, high blood pressure, palpitations, sweating, tremor and anxiety. When the autonomic nervous system is unbalanced with the parasympathetic system being more active, low blood pressure, slow heart rate, cold hands and feet and constriction of the pupil may occur. This is called vagotonia. Another principle symptom of orthostatic intolerance is intolerance to exercise.

Other parts of the nervous system are involved here as well. Misbehavior in the central nervous system can cause loss of consciousness, dizziness and cognitive issues. Malfunction of the vagus nerve can cause tachycardia, abdominal pain and nausea/vomiting.

There are three common forms of orthostatic intolerance.

Orthostatic hypotension is a consistent reduction of systolic blood pressure of more than 20 mm Hg or diastolic blood pressure of more than 10 mm Hg within three minutes of standing or a head up tilt of at least 60°. Orthostatic hypotension can occur for many reasons, including dehydration, blood loss or conditions that cause acute or chronic hypovolemia. Neurogenic OH is caused by insufficient norepinephrine released from cells of the sympathetic nervous system, causing inadequate vasoconstriction. Neurogenic OH typically occurs secondary to a systemic disease.

POTS patients suffer daily OI symptoms in conjunction with excessive tachycardia when standing, but not with low blood pressure. In adults, excessive tachycardia is defined as an increase of 30 bpm when standing or over 120 bpm. In children, excessive tachycardia is an increase of 40 bpm. Tachycardia is not sufficient for diagnosis; patients must also have OI symptoms. There are multiple subcategories of POTS, which I have previously covered and will cover in more detail elsewhere.

Postural syncope can be caused by acute orthostatic intolerance, simple fainting or vagovagal syncope (VVS). Syncope, also called fainting, is the loss of consciousness due to temporarily insufficient blood supply to the brain, followed by complete recovery. In short, this means fainting upon standing up. About 40% of people will faint at some point in their lives. About half of these people have their initial episode during adolescence, most around the age of 15. Syncope can be cardiovascular, from arrhythmia or structural abnormalities, or reflex/neurologic.

Mast cell disease (both mastocytosis and MCAS) has a known propensity for causing orthostatic intolerance.

References:

Stewart, Julian M. Update on the theory and management of orthostatic intolerance and related syndromes in adolescents and children. Expert Rev Cardiovasc Ther 2012 November; 10(11): 1387-1399.

Figueroa, Juan J., et al. Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med 2010 May; 77(5): 298-306.

Medow MS, Stewart JM, Sanyal S, Mumtaz A, Sica D, Frishman WH. Pathophysiology, diagnosis, and treatment of orthostatic hypotension and vasovagal syncope. Cardiol. Rev. 2008; 16(1):4–20.

Bayles R, Kn H, Lambert E, et al. Epigenetic modification of the norepinephrine transporter gene in postural tachycardia syndrome. Arterioscler. Thromb. Vasc. Biol. 2012; 32(8):1910–1916.

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 1

Deconditioning (also called cardiovascular deconditioning) is the acclimation of the body to a less strenuous environment and the decreased ability to function properly under normal conditions. This basically means that when you have less physical stress on the body for a certain period of time, like seen in bed rest, the body adapts to that level of functioning, so when you want to engage again in normal physical activities, it is difficult for your body. Deconditioning makes multiple systems of your body less functional.

Bed rest is the typical situation associated with deconditioning. Patients on bed rest lose muscle mass and strength rapidly.  1-3% of muscle strength is lost per day, with 10-20% decrease in a week’s time. If completely immobilized for 3-5 weeks, a patient can lose up to 50% of their strength. Loss of muscle mass is also a problem. Upper legs can lose 3% mass within a week of bed rest. The lower back and weight bearing muscles in the legs are most affected by loss of mass.

Within 24 hours of bed rest, your cardiovascular system is changing. In this time, your blood volume decreases 5%. In less than a week, 10% is lost; in two weeks, 20%. Resting heart rate also increases 4-15 bpm within the first month of bed rest. Laying down for so long means that blood that is normally in the lower part of your body is moved to the trunk. This causes excretion of water and salt, resulting in less plasma and blood volume.

In healthy controls, when you change position, your body rapidly moves fluid from one part of the body to others. This phenomenon is called fluid shifting. Normally, when moving from a laying position to standing, 500-700 ml of blood are moved from the trunk to the legs. This movement of fluid is called “functional hemorrhage”. Special nerve clusters called baroreceptors (which measure pressure in the blood vessels) tell the nervous system that there is less blood in the chest.   Your body then increases the heart rate, the force with which your heart beats, tightens up vessels so that they are less “leaky” and tells your body not to make urine temporarily. All of these functions allow your body to keep a normal blood pressure and adequate blood supply despite this large movement of fluid.

In healthy controls, when you lay down after standing, the reverse happens. 500-700 ml of fluid is rapidly transferred from the lower body to the trunk. This is called a “central shift”. This increase in fluid in the chest results in the veins returning more blood to the heart, increasing blood pressure. When the baroreceptors feel more pressure than usual from this added fluid, the heart rate and force with which the heart beats decrease, the vessels are relaxed so that fluids can move out of them more freely and your body begins to make urine again.

When you are deconditioned, your body does not make these changes correctly when you change position. The hallmark of deconditioning is reduced orthostatic tolerance. This means that when you change position, your body does not compensate correctly to maintain necessary blood pressure and adequate blood supply to the brain. Deconditioned patients often do not have sufficient blood volume to maintain blood pressure when standing. When they stand, their heart pumps out less blood than normal, so the heart starts beating faster to compensate. When it beats too fast, it is called tachycardia.

In addition to inability to maintain blood pressure correctly when changing positions, deconditioned patients also exhibit decreased blood volume pumped out by the heart, atrophy of heart muscle and decreased maximum oxygen consumption. These patients often have other forms of vascular dysfunction, diminished neurologic reflexes and reduced ability to exercise. A number of other systems are affected by deconditioning.

Though prolonged bed rest is the model with which deconditioning is most often associated, there is significant evidence that chronically ill patients may often be deconditioned, including those with chronic lower back pain, chronic fatigue syndrome, and rheumatoid arthritis.

References:

Munsterman et al. Are persons with rheumatoid arthritis deconditioned? A review of physical activity and aerobic capacity. BMC Musculoskeletal Disorders 2012, 13:202

Eric J. Bousema, Jeanine A. Verbunt, Henk A.M. Seelen, Johan W.S. Vlaeyen, J. Andre Knottnerus. Disuse and physical deconditioning in the first year after the onset of back pain. Pain 130 (2007) 279–286.

De Lorenzo, H. Xiao, M. Mukherjee, J. Harcup, S. Suleiman, Z. Kadziola and V.V. Kakkar. Chronic fatigue syndrome: physical and cardiovascular deconditioning. Q J Med 1998; 91:475–481.

Hasser, E. M. And Moffitt, J. A. (2001), Regulation of Sympathetic Nervous System Function after Cardiovascular Deconditioning. Annals of the New York Academy of Sciences, 940: 454–468.

Exercise and mast cell activity

Research on exercise induced bronchoconstriction represents a large body of work through which we can draw conclusions about mast cell behavior as affected by exercise.

Exercise has been found in a number of studies to induce mast cell degranulation and release of de novo (newly made) mediators. One study found that levels of histamine, tryptase and leukotrienes were increased following exercise in sputum of people with exercise induced bronchoconstriction. This same study found that in these patients, prostaglandin E2 and thromboxane B2 was decreased in sputum. Treating with montelukast and loratadine suppressed release of leukotrienes and histamine during exercise.

One important area of research is the interface between being asthmatic and being obese. Adipose tissue is known to release inflammatory molecules called adipokines. In particular, the adipokine leptin has been studied for its role in bronchoconstriction following exercise. Leptin (I did a previous post on leptin, which is also called the obesity hormone) enhances airway reactivity, airway inflammation and allergic response. It can also enhance leukotriene production. This last fact is interesting because obese asthmatics are less likely to respond to inhaled corticosteroids when compared to lean asthmatics, but both respond similarly to anti-leukotriene medications like montelukast.

LTE4 was found to be significantly higher in the urine of both obese and lean asthmatics following exercise. It was not increased in either obese non-asthmatics or healthy controls. Additionally, the level of LTE4 was significantly higher in obese asthmatics compared to lean asthmatics. In this same study, urinary 9a, 11b-PGF2 was elevated in both lean and obese asthmatics, but not in obese or healthy controls. The 9a, 11b-PGF2 level was also higher in obese asthmatics than lean asthmatics. The elevated LTE4 and 9a, 11b-PGF2 were found in urine testing rather than in sputum, indicating that these chemicals did not stay local to the lungs and airway.

It is thought that the high levels of leptin found in asthmatics drive the manufacture and release of leukotrienes and prostaglandins from mast cells, epithelial cells or eosinophils during exercise. Though the data are stacking up to look like this is the case, there has not yet been a definitive causal link established.

 

References:

Teal S. Hallstrand, Mark W. Moody, Mark M. Wurfel, Lawrence B. Schwartz, William R. Henderson, Jr., and Moira L. Aitken. Inflammatory Basis of Exercise-induced Bronchoconstriction. American Journal of Respiratory and Critical Care Medicine, Vol. 172, No. 6 (2005), pp. 679-686.

Hey-Sung Baek, et al. Leptin and urinary leukotriene E4 and 9α,11β-prostaglandin F2 release after exercise challenge. Volume 111, Issue 2, August 2013, Pages 112–117

 

Histamine depletion in exercise

A long known and often repeated finding is that regular exercise can be protective against asthma. This finding was published in 1966 by a group that found the airways of asthmatics grew progressively less reactive following intervals of exercise. This finding was confirmed by several studies that followed. At the time, the reason why exercise protected against reactive airways was unclear, but an early hypothesis was that mediators were depleted after the initial round of exercise and that time was required to restore them.

In the 1980’s, there was a wave of research around the role of histamine in airway reactivity of asthmatics. There were a few competing theories at this point for why asthmatics became less reactive following exercise: depletion of mediators, mainly histamine from mast cells; that bronchial smooth muscle became less responsive to stimulation by histamine via the H1 receptor; and that release of catecholamines (such as epinephrine) by exercise suppresses bronchoconstriction. A number of studies made relevant findings.

Histamine is known to be released in the lungs due to exercise. It is also known to become depleted and quickly metabolized. When exposed to histamine, asthmatics recover quickly from the ensuing bronchoconstriction. Some asthmatic patients show an increase in plasma histamine during exercise.

Plasma epinephrine does not rise in asthma patients as a result of exercise, or at the very least is metabolized almost immediately, and thus is unlikely to be protective. Bronchial smooth muscle was not found to become less responsive to histamine. This was demonstrated in a study that compared repeated inhalation of histamine (such as might be induced by exercise) with actual repeated exercise. This study found that repeated exercise diminished airway reactivity, while repeated inhalation of histamine did not.

Another report indicated that inhalation of cromolyn before exercise can prevent or mitigate exercise induced asthma in most patients. Administration of H1 inverse agonists was found to offer similar protection.

A more recent study (2012) looked at the role of histamine in fatigue from exercise. Histamine is now known to be involved in regulation of oxygen/carbon dioxide exchange, which is important in exercise. In mice that were persistently exercised, the level of histidine decarboxylase was increased. HDC is the enzyme that makes and immediately releases histamine in response to an immediate need. This is different from degranulation, in which histamine is made ahead of time and stored inside the cell until needed.

This study found that treating the mice with an H1 antihistamine, H2 antihistamine, or HDC inhibitor decreased endurance in the mice. Mice deficient in HDC or H1 receptors also had less endurance. This means that histamine is partly responsible for inducing tolerance to exercise and that blocking action of histamine causes fatigue to set in more quickly.

Treatment with fexofenadine, an H1 antihistamine, decreased levels of nitric oxide and glycogen in the muscles of exercised mice. Taken together, these findings mean that histamine protects against fatigue from exercise; that this effect is achieved via H1 receptors and production of nitric oxide; and that at least some of this histamine is provided by immediate production and release of histamine via HDC. This means that your body does not simply release its histamine stores in response to exercise; it makes it on the fly so as not to exhaust its supply.

 

References:

Hahn, Allan G., et al. Histamine reactivity during refractory period after exercise induced asthma. Thorax 1984; 39: 919-923.

Niijima-Yaoita, Fukie, et al. Roles of histamine in exercise-induced fatigue: favouring endurance and protecting against exhaustion. Biol Pharm Bull 2012; 35; 91-97.

Schoeffel, Robin E., et al. Multiple exercise and histamine challenge in asthmatic patients. Thorax, 1980, 35, 164-170.

Graham P, Kahlson G, Rosengren E. Histamine formation in physical exercise, anoxia and under the influence of adrenaline and related substances. J. Physiol., 172, 174—188 (1964).

McNeill RS, Nairn JR, Millar JS, Ingram CG.Exercise-induced asthma. Q J Med 1966; 35: 55-67.

 

Chronic urticaria and angioedema: Part 5

Chronic urticaria has a very well described stepwise treatment standard, which I will describe briefly here. If resolution is not achieved with the method described in one step, the next step is executed.

  • A second generation H1 antihistamine like cetirizine is begun with standard daily dosing. Triggers should be avoided wherever possible.
  • Dosage of second generation H1 antihistamine is increased.
  • Another second generation H1 antihistamine is added to the regimen. (For example, cetirizine and fexofenadine taken together).
  • An H2 antihistamine is added. About 15% of histamine receptors in the skin are H2, so some patients see benefit from this.
  • A leukotriene receptor antagonist like montelukast is added.
  • A first generation H1 antihistamine like diphenhydramine is added at bedtime.
  • A strong antihistamine like hydroxyzine or doxepin is added and dosages increased accordingly.
  • If all else has failed, consider addition of medications like Xolair, cyclosporine, or other immunosuppressants.

Treatment of angioedema is dependent upon the cause of the angioedema (C1 esterase deficiency, ACE inhibitor, etc). However, it is generally agreed upon that upper airway swelling, even if mild, should be treated aggressively. Intramuscular epinephrine is indicated for this situation, with advisories in numerous papers to administer epinephrine as early as possible if airway swelling is present.

Reactions caused by IgE are the most likely to respond immediately to epinephrine. Hereditary and acquired angioedema are less likely to respond to epinephrine. If the patient is on beta blockers, glucagon is the drug of choice, as beta blockers interfere with action of epinephrine.

I am doing a detailed follow up post on treatment options for the various types of angioedema.

 

References:

Jonathan A. Bernstein, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol Volume 133, Number 5.

Zuberbier T, Maurer M. Urticaria: current opinions about etiology, diagnosis and therapy. Acta Derm Venereol 2007;87:196-205.

Ferdman, Ronald M. Urticaria and angioedema. Clin Ped Emerg Med 2007; 8:72-80.

Chronic urticaria and angioedema: Part 4

There are a number of other conditions that present with similar features to chronic urticaria and angioedema.

Conditions that can present similarly to chronic urticaria are listed below.

Chronic urticarial vasculitis is associated with low or normal complement levels and confusingly can be a primary autoimmune disorder, or a process secondary to another autoimmune disease, like lupus. Urticarial vasculitis lesions sometimes resolve quickly but can last for several days. A lesion biopsy can distinguish between CU and chronic urticarial vasculitis. Painful or burning lesions suggest urticarial vasculitis, with raised lesions that don’t blanch, and may leave hyperpigmented areas in place of resolved lesions. Hepatitis B and C can cause urticarial vasculitis.

Swelling of the upper eyes can be mistaken for angioedema, but in some people may be a symptom of thyroid ophthalmopathy, thyroid driven eye disease. Development of urticaria for during pregnancy is not unusual. Cyclical urticaria can be from autoimmune progesterone dermatitis. Episodes of angioedema with accompanying weight gain can be caused by Gleich syndrome (episodic angioedema with eosinophilia).

Cutaneous mast cell patients demonstrate a variety of urticaria-like lesions, including urticaria pigmentosa, mastocytomas and telangiectasia macularis eruptive perstans. Mast cell activation syndrome can also cause angioedema and urticaria, but generally these are not the only symptoms.

Erythema multiforme looks like urticaria but is often due to viral infections, mycoplasma infections or some medications. Bullous pemphigoid can initially present with hive-like welts or small plaques that do not always blister in early disease. Swelling of the lips in the absence of eczema can indicate cheilitis granulomatosa.

Schnitzler syndrome can cause non-itching hives that exclude the face, bone pain and intermittent fevers. These patients also have IgM or IgG monoclonal gammopathy.

 

Angioedema in the absence of urticaria is rare. There are a few conditions that can cause it.

Hereditary angioedema (HAE) is caused by C1 esterase inhibitor deficiency (in type I, 80%-85% of cases); or dysfunction (in type II, 15-20%).  People with HAE do not have coincident urticaria. HAE is inherited in an autosomal dominant pattern, but up to ¼ of patients develop the condition through spontaneous mutation rather than through inheritance of the gene. About 40% of patients have their initial attacks before the age of 5.

Acquired angioedema (AAE) is caused by antibodies to C1 esterase inhibitor, which is usually caused by cancers of B cells. AAE is more likely to develop in older patients (usually fourth decade of life or later) and family history of angioedema is generally absent. AAE is also more likely to develop when an autoimmune disease or proliferative blood disorder is present.

Angioedema associated with these conditions can affect any part of the body, including limbs and abdomen. Patients with abdominal angioedema are often misdiagnosed as having an “acute” abdomen that requires surgical intervention. It is not unusual for patients to present initially only with abdominal swelling. Both HAE and AAE have a number of common triggers, including infection, emotional or physical stress. or trauma. Importantly, they are not caused directly by histamine and other mast cell mediators and as such are not responsive to antihistamines and corticosteroids.

There is also a form of angioedema specifically induced by treatment with ACE inhibitors. It can be relieved by discontinuing ACE inhibitor therapy.  Idiopathic angioedema can also occur in the absence of urticaria but is more likely to respond to prophylactic antihistamine use than HAE or AAE.

 

Edited to add: I removed the following line from the first HAE paragraph: “Type III is estrogen mediated and only found in adult women.”  This statement is inaccurate,  I mistakenly included i, as I had originally noted it when reading a paper from 2007.  I am doing a follow up post on HAE that will elaborate further on the different subtypes and treatment.  Many thanks to the reader who caught it!

 

References:

Jonathan A. Bernstein, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol Volume 133, Number 5.

Zuberbier T, Maurer M. Urticaria: current opinions about etiology, diagnosis and therapy. Acta Derm Venereol 2007;87:196-205.

Ferdman, Ronald M. Urticaria and angioedema. Clin Ped Emerg Med2007; 8:72-80.

Kanani, Amin, et al. Urticaria and angioedema. Allergy Asthma and Clinical Immunology 2011, 7(Suppl 1):S9.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Chronic urticaria and angioedema: Part 3

There are several pathways that can culminate in angioedema and urticaria.

Activation of mast cells by IgE is the most well known mechanism. When IgE binds to receptors on mast cells, several things happen. The mast cells release histamine. This in turn causes dilation of the nearby vessels and causes fluid to leak from the bloodstream into the tissues. This causes nerve cells to activate and release substance P, which also contributes to vasodilation and causes mast cells to release more histamine. In response to activation by IgE, mast cells will also produce PGD2 and leukotrienes C4 and D4.

The complement system is one of the ways our body identifies infectious agents and triggers the immune system to kill them. Complement proteins are in the blood all the time, and they can be activated by three distinct pathways, all of which are triggered by pathogens: the classical pathway, the alternative pathway and the lectin pathway. Regardless of which pathway activates the complement system, the molecules C3a, C4a and C5a are produced. These molecules bind to receptors on mast cells and induce histamine release.

Following initial dilation of local vessels, proteins that normally are found in the plasma move into the skin. This activates the kinin system, which produces bradykinin through a series of steps. Bradykinin is a very powerful vasodilator and contributes significantly to loss of volume from the blood stream to the tissues.

C3a, C5a, PGD2, and leukotrienes C4 and D4 all draw other inflammatory cells to the site of activated mast cells. These cells release further molecules to stimulate histamine release. This mechanism perpetuates inflammation beyond the original insult.

Bradykinin levels are normally controlled by the enzyme ACE. When patients take ACE inhibitor medications (like Lisinopril, etc), this interferes with bradykinin degradation and cause urticarial and angioedema.

C1 esterase inhibitor regulates complement and kinin pathways. In patients who are deficient in C1 esterase inhibitor, bradykinin may be overproduced.

Many autoimmune conditions cause the formation of IgG1 and IgG3 antibodies. These molecules can interfere with the complement system and cause production of fragments that activate mast cells, like C3a.

NSAIDs are well characterized in their ability to cause angioedema and urticaria. While the mechanism is not fully understood, it is thought that since NSAIDs stop production of prostaglandins, the mast cells overproduce leukotrienes, which contribute to the angioedema and urticaria.

There are several non-immunologic methods that can result in angioedema and urticaria. Heat or pressure on the skin; radiocontrast dyes; alcohol; vancomycin; opioids; and foods like shellfish and strawberries have been linked to these conditions.

 

References:

Jonathan A. Bernstein, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol Volume 133, Number 5.

Usmani N,Wilkinson SM. Allergic skin disease: investigation of both immediate and delayed-type hypersensitivity is essential. Clin Exp Allergy 2007;37:1541-6.

Zuberbier T, Maurer M. Urticaria: current opinions about etiology, diagnosis and therapy. Acta Derm Venereol 2007;87:196-205.

Ferdman, Ronald M. Urticaria and angioedema. Clin Ped Emerg Med2007; 8:72-80.

 

Premedication and surgical concerns in mast cell patients

The exact incidence of immediate anaphylaxis from anesthesia or surgery in mastocytosis patients (or mast cell patients, more generally) is not known. Only a handful of these events have been reported in literature; however, it is likely that the majority of uneventful procedures were not tracked, so statistics are unclear. To date, there have been no controlled trials investigating anesthetics in mast cell patients.

In 2014, a paper was published entitled “Perioperative Management of Patients with Mastocytosis.” This paper is excellent and addresses the specific issues that may arise for mast cell patients before, during and after surgery. I recommend you provide this reference to any doctor involved in your surgical/procedural care that is unfamiliar with mast cell disease.

Mastocytosis patients are at risk for activation by a number of triggers, some of which cannot be avoided in the surgical setting. For this reason, suppression of mediator release in advance of surgery is recommended. The following pre-medication protocol is recommended for mast cell patients for all major and minor procedures and for radiology procedures with and without dyes:

  • Prednisone 50mg orally (20mg for children under 12): 24 hours and 1-2 hours before procedure
  • Diphenhydramine 25-50mg orally (12.5 mg for children under 12) OR hydroxyzine 25mg orally, 1 hour before procedure
  • Ranitidine 150mg orally (20mg for children under 12) 1 hour before procedure
  • Montelukast 10mg orally (5mg for children under 5) 1 hour prior to procedure

This protocol was developed for the Mastocytosis Society by Dr. Mariana Castells and the original can be found here: http://www.tmsforacure.org/documents/ER_Protocol.pdf

 

Common triggers for mast cell patients in this setting include:

  • Anxiety and psychological stress regarding the procedure. Administration of medication to mitigate anxiety (benzodiazepines, etc) is recommended to avoid mast cell degranulation. It is preferable for mast cell patients to be the first surgery of the day if possible, and for a quiet, calm atmosphere to be maintained in the OR.
  • Temperature changes. Either being too cold or too hot can culminate in a mast cell reaction. Constant monitoring of patient’s temperature is required. Additionally, the OR temperature should be monitored. Head coverings, warming mattresses, and forced-air warming systems can be used to prevent hypothermia. Infusion and irrigation solutions should be warmed, and anesthetic gases should be warmed wherever possible.
  • Irritation of the skin (including use of tourniquet). This can cause mast cell degranulation that leads to urticaria, especially in patients with cutaneous mastocytosis. Blisters may form with pressure from tourniquet or face mask. Mast cell degranulation of this type releases chymase which can lead to edema.
  • The inherent physical trauma associated with surgery. This is of specific consideration when operating in the GI tract, which has a significant mast cell population relative to other organs.
  • Musculoskeletal pain from skeletal involvement in SM patients. Patients should be positioned carefully to avoid causing fractures.
  • Pain can cause mast cell degranulation. For this reason, opioid medications should be used for pain relief wherever possible.

 

Reference:

Pascale Dewachter, M.D., Ph.D.; Mariana C. Castells, M.D., Ph.D.; David L. Hepner, M.D., M.P.H.; Claudie Mouton-Faivre, M.D. Perioperative Management of Patients with Mastocytosis. Anesthesiology 03 2014, Vol.120, 753-759.

The opposite of being alone

Last Thursday morning, I flew to Los Angeles for the long awaited meeting with my mastsister Addie and her family. I arrived at Logan Airport two hours before my flight. I have flown seven times in the last year so I am overly familiar with the routine. I carry on one suitcase with medical supplies and clothes, a laptop bag with my computer and my backpack that holds my IV supplies and infusion pump. I carry a letter from my doctor stating I need these things when I travel; aside from the fact that the large fluid bags are always swabbed for explosives, it is never a problem.

I was deposited at the gate almost an hour before my flight. Anytime I book a flight, I call the airline to reiterate that I need to infuse while I fly. They always seat me in the first row so there is more room for people to navigate past me when leaving the row. I have been advised that since the IV line is attached to my body, the FAA views it the same way as an insulin pump, and that I just have to hold it in my lap while we take off and land.

The gate agent came over and began asking questions about my backpack and IV fluids. I told him that it is attached to me, showed him the bag and pump, provided my letter. He and his supervisor made several phone calls and peered at me from behind the counter while talking about me in hushed voices.

The man came back over and asked if I had a fit to fly form. Most of the flights I have taken this year were with this same airline; I took two flights with them just over a month ago. I have never been asked to provide this form and would have gotten one had I been told to.

They continued calling people. I was now the only person not boarded and getting pretty irritated. I walked over to the counter and asked them what was going on.

“If you need IV fluids, then our medical team says you can’t fly,” he told me.

I explained that I had done this several times in the last year and had a note from my doctor that says “Lisa needs the following medications on her person when flying” which would obviously not have been proffered if I couldn’t fly. I explained about my disease and that I have lived with it for a long time and was fully capable of handling any symptoms. They decided I could board the plane but stopped me feet from the plane. The pilot came out and asked further invasive questions about my health and about my IV fluids, which had already cleared security. (In case you’re all wondering, the answer is that no, my IV fluids are not explosive.)

They let me board and the entire population of the plane stared at me while the crew discussed whether or not I was, in their estimation, healthy enough to fly. With their exchanged looks, I felt my personhood being stripped away. All that was left was a complication.

I keep thinking about that other life, before I looked sick enough that a gate agent felt entitled to ask me deeply personal questions about the state of my health. I did so many things. I went to a lot of places. I was able, physically and mentally. And now I’m… not able? Unable? I don’t know what I am, but whatever it is, I’m not the same.

It’s hard to live in the present sometimes. It’s hard not to compare everything I do to a previous iteration that came before I got sick. I can feel myself walking backwards, covering every step I took to get here, trying to find the moment when my fate was sealed. I wonder if I had known back then what was wrong if it would have made a difference. I wonder if I would still be this way, if I would still be unable.

I landed in Los Angeles six hours later without so much as a mast cell hiccup, my infusion pump clicking along happily. Addie and I compared ports and medicines and discussed Frozen at length.  We camped at Newport Beach this weekend and met up with some other masto friends. Ten people with mast cell disease on a beach by the bay, looking for dolphins in the evening light. Ten people with mast cell disease swimming and accessing ports and taking Benadryl and listening to coughs and eating smores. It was calm and breezy and safe. It was the opposite of being alone.

Me and Addie

 

Chronic urticaria and angioedema: Part 2

CU lesions are swollen pink or red wheals, of variable size, often with surrounding redness. They are generally itchy rather than painful or burning. Angioedema is not itchy, brawny, of a non-pitting quality with indistinct margins and without redness.

There are a number of chronic urticaria and angioedema (CU) subsets that are triggered by environmental sources. These are called physical urticarias.

In aquagenic urticaria, patients develop hives after contact between water and the skin. Temperature is not a factor in this type of urticaria. The hives are generally “pinpoint”, measuring 1-3mm. This is confirmed by applying a water compress at near body temperature to the skin of the upper body for 30 minutes.

Cholinergic urticaria also causes pinpoint hives, but these hives are surrounded by large flare reactions as a result of increased body temperature. Exercise, sweating, emotional stress, hot baths and showers are all frequent triggers of this subtype. Cholinergic urticaria can be benign or life threatening. Testing involves exercise or hot water immersion as these activities raise the core body temperature.

Cold urticaria results in hiving when the skin is exposed to a cold source. Patients may have systemic reactions in the event of full body exposure to the cold (swimming in cold water, etc). This is tested by placing an ice cube on the patient’s skin and waiting for a reaction, which occurs when the skin starts to warm.

Delayed pressure urticaria/angioedema presents as swelling, which may be painful, after the skin is exposed to pressure. While 4-6 hours is a more typical duration for symptoms to present, in some patients it can take 12-24 hours. Working with tools, sitting on a bench, wearing tight clothing, and carrying a heavy purse are all representative triggers. Testing for this subtype involves placing a 15 lb weight on the patient’s shoulder for 10-15 minutes, then waiting for response. Angioedema at the site that evolves following this test is considered a positive test, regardless of whether or not weals are present. This type can be difficult to treat.

Dermatographia is the most common type of physical urticaria. 2-5% of the general population have dermatographia.   Stroking the skin firmly causes a weal and flare reaction where the skin was touched. It does not usually require treatment.

Exercise induced anaphylaxis has two types: those in whom anaphylaxis in provoked strictly by exercise, and those in whom anaphylaxis is triggered when a specific food is consumed prior to exercise. Cholinergic urticaria can also be triggered by exercise, so it is important to distinguish between the two. Exercise anaphylaxis can only be triggered by exercise, whereas cholinergic urticaria results if the patient becomes too hot. People with exercise induced anaphylaxis need to carry epipens and must not exercise alone as reactions can be severe.

Solar urticaria is the development of hives when the skin is exposed to sunlight, generally within minutes. Solar urticarial is further divided in subtypes based upon which wavelengths of light are triggering to the patient. Testing involves lightbox exposure to isolated wavelengths of light. It is distinct from polymorphous light eruption, in which onset is often delayed and can last for days. It can cause papules, papulovesicles and plaque manifestations on the skin.

Recall urticaria is hiving at the site of a previous sting or injection when exposed again to the same trigger.

Vibratory angioedema causes itching and swelling when the skin is exposed to a vibration source. This specific type can show a familial trait. It is confirmed by showing a response after use of a vortex mixer (a piece of lab equipment that mixes solutions in tubes).

 

References:

Jonathan A. Bernstein, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol Volume 133, Number 5.

Usmani N,Wilkinson SM. Allergic skin disease: investigation of both immediate and delayed-type hypersensitivity is essential. Clin Exp Allergy 2007;37:1541-6.

Zuberbier T, Maurer M. Urticaria: current opinions about etiology, diagnosis and therapy. Acta Derm Venereol 2007;87:196-205.