Management of the peripartum period in a mast cell patient

I’ve been getting a lot of questions about pregnancy and delivery in mast cell patients. I had an interesting case a couple of years ago that I thought people might find illuminating. I contacted the patient and she had no problem with me sharing her case.

The case involved a pregnant mast cell patient experiencing both cardiovascular and mast cell driven complications of the pregnancy with significant risk of preterm delivery. I worked with the patient and her care team to develop a plan to minimize the risk of mast cell activation and anaphylaxis both before and after delivery. Mom delivered by Cesarean and had no complications during or after delivery. Baby also suffered no complications associated with birth.

This is some of the material I provided to her team.

Overview:

Mast cell disease is a group of proliferative and non-proliferative conditions that is hallmarked by severe allergic reactions and anaphylaxis to triggers by non-IgE pathways. Due to the the diverse role of mast cells in many processes, including allergy, immune defense, wound healing and reproduction, mast cell degranulation and activation is an ever present threat.

Premedication:

Mast cell patients are recommended to premedicate prior to any procedure, including non-invasive procedures, to suppress mast cell activation.

24 hours before:
50mg prednisone

1-2 hours before:
50mg prednisone
50mg diphenhydramine
150mg ranitidine
10mg montelukast

An IV protocol used by some patients in place of the oral meds at 1-2 hours:
50mg diphenhydramine
40mg famotidine
40mg methylprednisolone

Following procedures/medical events/anaphylaxis, some patients do best with a taper of antihistamines and steroids to suppress rebound reactions and biphasic anaphylaxis in the following days. An example of this regimen is:

Antihistamine support:
-50mg diphenhydramine IV every 4 hours for first 24 hours
-50mg diphenhydramine IV every 6 hours for next 48 hours
-50mg diphenhydramine IV prn thereafter

Corticosteroid coverage:
Corticosteroids play an integral role in modulating mast cell activation. In the days following procedures/medical events/anaphylaxis, some patients do best with a steroid taper. Please note that the reason for the taper is NOT to prevent adrenal insufficiency, but to provide adequate steroid coverage to suppress mast cell reactions at a time when a non-mast cell patient would safely tolerate an abrupt cessation of steroids.

There is no defined protocol, but many patients use a Medrol dosepak or seven day prednisone taper following anaphylaxis and do well with this protocol following other procedures/events.

Cardiovascular concerns:

In cardiac patients with mast cell disease, Kounis Syndrome (allergic angina/MI) is a risk. In this condition, patients experience angina/MI as the result of a histamine driven process. Mast cell rescue medications (diphenhydramine, famotidine, methylprednisolone) should be given along with appropriate management of cardiovascular symptoms (nitroglycerin, calcium channel blockers). Epinephrine can be used if appropriate.

Beta blockers are a hard contraindication for mast cell patients as they interfere with the action of epinephrine. Use of beta blockers is commonly cited as a risk factor for fatal anaphylaxis. ACE inhibitors are often not recommended due to interaction with the angiotensin/renin system in which mast cells actively participate.

Pain management:

Most opiates are not recommended for mast cell patients due to induction of mast cell degranulation. Fentanyl and hydromorphone are the ones most often used successfully and are the drugs of choice for acute pain management.

Literature findings:

Ciach K, et al. Pregnancy and delivery with mastocytosis treated at the Polish Center of the European Competence Network on Mastocytosis (ECNM). PLoS One 2016; 11(1): e0146924

  • Five women delivered via cesarean. In one patient, the cesarean was performed specifically because of concerns about vaginal delivery in a mastocytosis patient. In the other four cases, cesarean was performed because of preeclampsia; improper positioning of the fetus; lack of labor progression; and large size of the fetus’ head relative to the size of the uterus. In all of these cases, spinal anesthesia was used with no complications.
  • Twelve women delivered vaginally without complications. In two patients, an epidural was used for pain management. In three patients, medication (oxytocin) was used to induce uterine contraction.
  • Four patients experienced pregnancy complications in the second trimester. The complications were pregnancy induced hypertension and swelling of the extremities; deep thrombosis (blood clot formation); toxoplasmosis, an infection; preterm labor without delivery; and vaginal bleeding in the first trimester.
  • Four patients delivered early, at 26 weeks, 36 weeks, and 37 weeks. The woman who delivered at 26 weeks had preeclampsia and her baby died less than a month after delivery due to extreme prematurity. Twelve patients delivered full term. Three babies had low birth weight upon delivery.
  • Mastocytosis patients are at higher risk of complications that involve clotting. Mast cell patients often experience coagulation irregularities, such as blood clot formation.
  • There have been three cases reported in literature of mastocytosis patients who developed preeclampsia that required preterm delivery.
    In order to suppress mast cell reactions and anaphylaxis, patients were premedicated before delivery with antihistamines and corticosteroids. Another study on pregnancy in mastocytosis reported that even with premedication, some patients still experienced mast cell activation during or after labor.
  • Epinephrine, antihistamines and glucocorticoids (steroids) should be readily available during and after labor

Matito A, et al. Clinical impact of pregnancy in mastocytosis: A study of the Spanish network on Mastocytosis (REMA) in 45 cases. Int Arch Allergy Immunol 2011; 156: 104-111.

  • 22% (10) of patients delivered via caesarean. 78% (35) delivered vaginally.
    Nine patients required labor induction. Oxytocin was used in eight cases and dinoprostone was used in one case.
  • Premedication for mast cell activation with antihistamines and glucocorticoids was only given to 38% (17) of patients.
  • 82% (37) of patients received anesthesia. 32 patients received epidurals; 3 received local anesthesia; and 2 received general anesthesia.
  • 11% of patients had mast cell activation symptoms, including flushing and itching, during or just following labor.

Dewachter P, et al. Perioperative management of patients with mastocytosis. Anesthesiology 2014, 12): 753-759.

  • Mastocytosis symptoms can improve, worsen, or remain unchanged during pregnancy.
  • Anesthesia management of mastocytosis patients has not been well described, with 13 CM patients and 33 SM patients mentioned in literature since 2000.
  • In one instance, IV epinephrine was necessary following labor to manage low blood pressure and difficulty breathing in an SM patient.
  • Early use of epidural anesthesia is recommended for mastocytosis patients to manage pain as pain triggers mast cell degranulation.
  • Patients should continue their regular medications to manage mast cell disease until the day of surgery.

GI scoping in mast cell patients

• Mast cell patients often need gastrointestinal scoping procedures to investigate the cause of dominant GI symptoms or see the full extent of GI organ inflammation, dysfunction or failure.

• GI scoping procedures for mast cell patients require thoughtful preparation due to the many triggers these procedures present. Overwhelmingly, GI scoping is performed safely in mast cell patients.

• An IV is placed before the start of the procedure. It is not unusual for mast cell patients to be “hard sticks”, meaning that it is hard to place an IV. There are several reasons that this happens.

• Mast cell disease causes significant third spacing, a phenomenon in which the fluid is the bloodstream falls out of the bloodstream and gets stuck in tissues. This means that mast cell patients may not have as much fluid in their bloodstream as they should, causing functional dehydration. Dehydration causes the blood vessels to be smaller and more tense.

• Mast cell inflammation is linked to hardening of blood vessels over time, making it harder to get an IV into the vessel.

• Many mast cell patients have connective tissue disorders like Ehler Danlos Syndrome. In these patients, their connective tissue may not properly hold the blood vessels in the right place, making it harder to get an IV into the vein.

• I have a weird observation to add to the “Reasons IV’s are difficult to place in mast cell patients” list. I have found that for the past fifteen years, anytime I had an IV removed, something weird happened. There was some kind of deposit at the IV site. It felt “sandy” and kind of “crunchy”. Whatever was there was solid as I was able to roll it up and down the blood vessel in my arm. I now refer to this as “mast cell deposition” for want of a better term. Once the deposit was gone, which would take weeks, I could no longer get an IV at that site or below it. They would try to place an IV in one of those spots and it hurt a lot and just wouldn’t work. It was bizarre. All of my doctors are stumped. I have two theories: local mast cells have a huge inflammatory response that attracts way more immune cells that normal; or,  that those little sandy bits are platelets all clumped together since mast cells release platelet activating factor. This is purely speculation. Does this happen to anyone else?

• If you are allergic to adhesives like Tegaderm, be aware at Tegaderm is what comes in IV kits to put over the IV once it is placed. If you react to Tegaderm, be sure to remind your nurse when placing the IV that you cannot use Tegaderm and will need another kind of dressing. 

Moist heat can help blood vessels to relax and become larger, making them easier to find and to place an IV there. What worked for me was running a facecloth under really hot water, wringing it out, and letting the facecloth sit on my arm for about ten minutes before attempting to draw blood.

Mast cells are involved in inflammation of the blood vessels. If the mast cells irritate the blood vessels enough, vasculitis can occur. This may be local (close to the site of the IV) or diffuse (more widespread and affection many blood vessels.) Mast cell patients may develop vasculitis from the IV.

GI scoping is performed with twilight sedation. Typically, IV medications are given to patients to help with the discomfort and anxiety associated with procedure. These medications including propofol, midazolam, and fentanyl. There are no particular concerns for the use of these medications in mast cell patient. (These are the meds I use when I get scoped.)

Mast cell patients should premedicate prior to GI scopes starting the day before the procedure. The general recommendation for premedication uses H1 and H2 antihistamines, leukotriene inhibitors, and corticosteroids. You can find this protocol here:
- Prednisone 50 mg orally (20mg for children under 12) 24 hours and 1-2 hours before procedure
- Diphenhydramine 25-50 mg orally (12.5 mg for children under twelve) 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

Premedication is given in addition to regular daily meds.

• A number of patients, including myself, find that using IV antihistamines and corticosteroids before the procedure works better for us. I personally find this to be the case for me. Patients should work with their care team to amend their individual premedication procedure if necessary. My premedication protocol is:
- Prednisone 50mg orally 24 hours before procedure
- Diphenhydramine 50mg IV 1 hour before procedure
- Famotidine 40mg IV 1 hour before procedure
- Solu-medrol 40mg IV 1 hour before procedure

• Patients should be aware that IV diphenhydramine (Benadryl) is sclerotic to blood vessels. This means that the use of IV Benadryl can irritate or damage blood vessels. If using the IV Benadryl in a regular peripheral IV, this could cause irritation of the blood vessels. Dilution of the medication and pushing it slowly through the IV can help to avoid this.

• I personally dilute IV Benadryl in saline (1mL of Benadryl to 9mL of normal saline) and push it through the port over five minutes. I then push the saline flush over five minutes. Last summer, I had a midline placed so that I could deaccess my port in the hopes the ulcer at my access site would heal. A midline is basically one step above a regular IV. They aren’t intended for long term use and they aren’t central lines. Medication pushed through it enters the body is a small vein. With central lines like ports, the medication enters the body into a very large vein that blood is moving through very quickly. I got a really nasty case of local vasculitis from pushing benadryl through the midline. I was diluting each dose 1mL of Benadryl to 50mL of saline and it still hurt. We had to pull the midline after only nine days and I had to go back to using my port. Patients should work with their care team to determine if dilution and slow pushing is necessary in their individual cases.

Touching the GI tract from the inside causes massive mast cell activation. This triggers huge degranulation of mast cells throughout the GI tract. The chemicals released can trigger the activation of mast cells in other parts of the body. The degranulation of mast cells in the GI tract also contributes to a condition called ileusPremedication helps to lessen the severity of activation and degranulation.

Patients should not have to discontinue mast cell medications prior to scoping. If patients are on NSAIDs to block prostaglandin production, like aspirin, the provider may request that this med be skipped on the day of the procedure. However, this is at the discretion of the provider and is a decision specific to each patient. (Author’s Note: Many thanks to MastAttack admin Pari who reminded me of an important note regarding meds and biopsies. A number of mast cell patients also have eosinophilic GI disease. When biopsying for EGID, use of steroids, which is part of the mast cell premed protocol, will skew the results. Mast cell patients who have EGID or who are suspected to have it should speak with their care team about whether or not they need to avoid steroids and for how long in advance of a scope.)

• Patients may find their symptoms are worse than baseline in the days following the procedure. Many people find that increasing antihistamines for a few days can help to mitigate these symptoms. For example, some people do a Benadryl taper. I used to do the same before I ended up taking Benadryl every day. It goes like this:

Day One: 50mg Benadryl ever 4 hours

-Day Two: 50mg Benadryl every 6 hours

-Day Three: 50mg Benadryl every 6 hours

-Day Four: 50mg Benadryl every 12 hours

-Day Five: 50mg Benadryl every 12 hours

Patients should discuss this with their care team to see if this is appropriate for them.

• For many patients, the hardest part of lower GI scoping is the bowel prep. Bowel preping is inherently mast cell activating. Everyone has mast cells in their GI tract. Mast cell patients often have more mast cells than usual in their GI tract. The bowel prep procedure increases GI motility, leading to mast cell activation. Patients should be aware that these increased symptoms, while unpleasant, are not generally dangerous. Patients should ask their care team whether or not they should discontinue the prep or go to the emergency department if certain severe symptoms occur.

• The standard prep for colonoscopies uses some version of polyethylene glycol, things like Miralax or Golytely. Like everything else, there is no way to predict whether or not a patient with react to it. There are alternative preparation protocols for people who can’t use polyethylene glycol. My prep plan is as follows:
 Two days before the scope: 1 bottle of magnesium sulfate, 600mg oral docusate sodium, consume clear fluids only
- One day before the scope: 1 bottle of magnesium sulfate, 600mg oral docusate sodium, consume clear fluids only
- The day of the scope: 2 saline enemas, the first one given two hours before leaving the house, the second one given one hour before leaving the house

• Biopsies should be taken during scopes. Mast cells can cause inflammation on the cellular level and the tissue may be inflamed despite looking normal during the scope.

• Biopsies should be tested using immunohistochemistry (IHC) for the markers CD117, CD2, and CD25. CD117 will show any mast cells present. CD2 and CD25 are markers that are found on the mast cells of many patients with systemic mastocytosis.

• Sometimes providers order the lab to look for mast cells using regular microscopy staining instead of IHC. Toluidine blue and Giemsa-Wright are both stains that can show mast cells. However, IHC is much more accurate than using these stains. Mast cells could be missed by using these stains instead of IHC.

There is not usually enough mast cell DNA in GI biopsies to accurately test for CKIT D816V mutation, a DNA mutation that is associated with mastocytosis.

• You can find additional information on how to test these biopsies here.

There is not a universal way to report the number of mast cells seen with microscope in a GI biopsy that has been put on a slide. One of the more common ways to do this is to count the mast cells in five different high powered microscopy fields (hpf) and then average the counts.

There was an excellent paper published in 2014 called “Perioperative Management of Patients with Mastocytosis.” It is free and publicly available. You can find it here. I encourage you to bring this paper with you to the appointment. The paper discusses all the triggers we experience from surgery and how to medicate patients properly for the procedure. Even though GI scoping is not the same as surgery, the vast majority of advice on surgery in mast cell patients also applies to scoping procedures.

For further reading, please visit the following posts:

Premedication and surgical concerns in mast cell patients

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 5

Third spacing

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 56

70. What is premedication and when should I do it?

Premedication is taking extra medication in advance of doing something that you expect to trigger your mast cells. The current premedication protocol for mast cell patients is as follows:
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.

This premedication protocol uses medications to interfere with the molecules mast cells release as well as medication to decrease the amount of molecules mast cells make and release. Diphenhydramine (called Benadryl in the US) stops histamine from getting to the H1 histamine receptors on the outsides of many cells. Ranitidine stops histamine from getting to the H2 histamine receptors on the outsides of many cells. In these ways, these medications can help to stop symptoms from histamine released by mast cells.
In a similar way, montelukast stops leukotrienes from getting to receptors on cells. This helps to curb some of the symptoms that occur when leukotrienes are released by mast cells.

Prednisone is a glucocorticoid, commonly called referred to as a “steroid.” This medication suppresses the production and release of inflammatory molecules by mast cells and other immune cells. Importantly, this medication can take hours to achieve maximum effect. This is why the first dose is the day before the event for which you are premedicating. By being dosed again a couple of hours before the event, it can also provide some additional protection for delayed reactions.

It is important to know that this premedication protocol may need to be changed to achieve the most effective protocol for individual patients. These recommendations are general and are not based upon study or clinical trial data.

This procedure is intended to be used for all major and minor medical procedures, including imaging tests like x-rays and MRIs, whether or not they use contrast. However, many patients find some benefit in premedicating for other types of events as well, such as flying, childbirth, and days of planned elevated physical or emotional stress. Patients should discuss what sorts of events are appropriate to premedicate for with a knowledgable provider.

For more detailed reading, please visit the following post:
Premedication and surgical concerns in mast cell patients

The Provider Primer Series: Relevance of mast cells in common health scenarios (continued)

Reason for care Post op care
Role of mast cells Mast cells are inherently activated following surgery as they drive tissue remodeling, angiogenesis, and wound repair.[i]

Mast cells are involved in the transmission of pain stimuli.[iii]

Impact of condition on mast cells Mechanical trauma or pressure, such as dressing a wound or palpating the area, can directly induce degranulation and mast cell activation[ii].

Pain can trigger mast cell activation.[iii]

Psychological and physical stress can trigger an inflammatory response that involves mast cell activation.[iv]

Notes regarding condition treatment NSAIDS can trigger mast cell degranulation and cannot be taken by some mast cell patients.[iv]

Codeine and derivatives can trigger mast cell degranulation[v].

Vancomycin, gyrase inhibitors and cefuroxime should be avoided where possible due to risk of mast cell activation.[vi]

Amide caine anesthetics are preferred over ester caines.[vi]

ACE inhibitors and β-adrenergic receptor antagonists (beta blockers) should be avoided. In particular, beta blockers directly interfere with the action of epinephrine and can impede anaphylaxis management.[vi]

Fentanyl and fentanyl derivatives are the preferred narcotic for mast cell patients due to low risk of degranulation. Hydromorphone and oxycodone are suggested by some authors and see use in mast cell patients.[vi]

Benzodiazepines can provide anxiolytic and anticonvulsive support in mast cell patients are needed.[vi]

IV contrast poses significant to mast cell patients due to the high risk of systemic degranulation. If required, premedication is advised.[vi]

Adhesive allergy is not unusual and patients may require specific occlusive dressings, tapes, or wound glue.

Notes regarding mast cell treatment Antihistamines and mast cell stabilizers can be helpful in mitigating common post op symptoms such as opiate induced itching and nausea. COX inhibitors can help with pain management.[vii]
Special considerations for mast cell patients Mast cells are the largest reservoir of endogenous heparin. Patient should be monitored for coagulopathy.[viii]

Mast cells contribute significantly to post operative ileus.[ix]

Intestinal manipulation directly results in mast cell degranulation.[ix]

 

Reason for care Hypertension
Role of mast cells Mast cell mediators can impact blood pressure. Histamine acting on H2 receptor can promote hypertension.[xi]

Renin, chymase, and carboxypeptidase A all participate in hypertension by dysregulation of angiotensin II.[xi]

9a,11b-PGF2, the degradation product of prostaglandin D2, thromboxane A2, and leukotrienes increase blood pressure.[xi]

Impact of condition on mast cells Dysregulation of angiotensin II and renin levels can affect mast cell behavior.[x]
Notes regarding condition treatment ACE inhibitors and β-adrenergic receptor antagonists (beta blockers) should be avoided. In particular, beta blockers directly interfere with the action of epinephrine and can impede anaphylaxis management. Alternatives include calcium channel blockers, renin inhibitors, and ivabradine, among others.[vi]
Notes regarding mast cell treatment Several mast cell medications can impact levels of histamine, renin, and angiotensin II, all of which can affect blood pressure.
Special considerations for mast cell patients Mast cell patients taking β-adrenergic receptor antagonists (beta blockers) should carry a glucagon pen to increase efficacy of epinephrine in anaphylaxis.[xi]

As many as 31% of patients with mast cell disease demonstrate elevated arterial blood pressure secondary to mast cell activation. These elevations may be episodic or chronic.[xi]

Mast cell patients may also have hyperadrenergic postural orthostatic tachycardia syndrome (hyperPOTS), a condition that can cause hypertension.[xii]

 

Reason for care Heart disease
Role of mast cells Renin, chymase, and carboxypeptidase A all participate in hypertension by dysregulation of angiotensin II, contributing to evolution of arrhythmia.[xi]

Prostaglandin D2, VIP, PAF, IL-6 and nitric oxide are all vasodilating and can contribute to tachycardia.[xi]

Tryptase, histamine, PAF, IL-10, TNF, IL-4, IL-6, FGF, and TGFB can contribute to heart failure.[xi]

Mast cells participate in the formation, destabilization and rupture of atherosclerotic lesions.[xiii]

Histamine release is associated with acute coronary syndromes such as Kounis Syndrome, commonly known as “allergic MI” or “allergic angina”.[xiv]

Leukotriene C4, adrenomedullin, tryptase and chymase participate in the formation, destabilization and rupture of aneurysms.[xiii]

Impact of condition on mast cells Heart disease, especially heart failure, can disrupt release of catecholamines including norepinephrine.[xv] Norepinephrine dysregulation can impact mast cell behavior.

Dysregulation of angiotensin II and renin levels can affect mast cell behaviorx

Notes regarding condition treatment NSAIDS can trigger mast cell degranulation. Some mast cell patients are unable to take them.xx

Acetaminophen is generally recommended for use in mast cell patients.[iv]

ACE inhibitors and β-adrenergic receptor antagonists (beta blockers) should be avoided. In particular, beta blockers directly interfere with the action of epinephrine and can impede anaphylaxis management. Alternatives include calcium channel blockers, renin inhibitors, and ivabradine, among others.[vi]

Notes regarding mast cell treatment COX inhibitors are routinely taken by mast cell patients and may provide relief of prostaglandin induced symptoms.[vi]

Several mast cell medications can impact levels of histamine, renin, and angiotensin II, all of which can affect blood pressure.

Epinephrine can provoke myocardial ischemia, prolong QT interval, and exacerbate coronary vasospasm and arrhythmia.[xiv]

Special considerations for mast cell patients Over 20% of systemic mastocytosis and mast cell activation syndrome patients experience palpitations and supraventricular tachycardia.[xi]

Prostaglandin D2 can cause tachycardia. PGD2 is associated with late phase allergic response and symptoms may be delayed for several hours after allergic event.[xi]

One study showed that 12/18 mast cell activation syndrome patients showed diastolic left ventricular dysfunction.[xi]

Mast cell patients may also have postural orthostatic tachycardia syndrome (POTS), a condition that can cause blood pressure and heart rate irregularities.[xii]

 

Reason for care Chest pain
Role of mast cells Mast cells participate in the formation, destabilization and rupture of atherosclerotic lesions.[xiii]

Histamine release is associated with acute coronary syndromes such as Kounis Syndrome, commonly known as “allergic MI” or “allergic angina”.[xiv]

Leukotriene C4, adrenomedullin, tryptase and chymase participate in the formation, destabilization and rupture of aneurysms.[xiii]

Mast cells participate in esophageal inflammation in several models, including from acid reflux.[xvi]

Mast cells contribute to GI dysmotility which can cause esophageal spasms.[xvii]

Mast cells are involved in the transmission of pain stimuli.[iii]

Impact of condition on mast cells Pain can trigger mast cell activation.[iii]

Psychological and physical stress can trigger an inflammatory response that involves mast cell activation.[iv]

Notes regarding condition treatment NSAIDS can trigger mast cell degranulation. Some mast cell patients are unable to take them.xx

Acetaminophen is generally recommended for use in mast cell patients.[iv]

Fentanyl and fentanyl derivatives are the preferred narcotic for mast cell patients due to low risk of degranulation. Hydromorphone and oxycodone are suggested by some authors and see use in mast cell patients.[vi]

Benzodiazepines can provide anxiolytic and anticonvulsive support in mast cell patients are needed.[vi]

ACE inhibitors and β-adrenergic receptor antagonists (beta blockers) should be avoided. In particular, beta blockers directly interfere with the action of epinephrine and can impede anaphylaxis management. Alternatives include calcium channel blockers, renin inhibitors, and ivabradine, among others.[vi]

Notes regarding mast cell treatment COX inhibitors are routinely taken by mast cell patients and may provide relief of prostaglandin induced symptoms.[vi]
Special considerations for mast cell patients Mast cell patients may experience GI dysmotility which can cause esophageal spasms.[xviii]

Mast cell patients sometimes have eosinophilic esophagitis, causing esophageal spasms, food impaction, and pain.[xix]

Over 20% of systemic mastocytosis and mast cell activation syndrome patients experience palpitations and supraventricular tachycardia.[xi]

Prostaglandin D2 can cause tachycardia. PGD2 is associated with late phase allergic response and symptoms may be delayed for several hours after allergic event.[xi]

One study showed that 12/18 mast cell activation syndrome patients showed diastolic left ventricular dysfunction.[xi]

Mast cell patients can present with Kounis Syndrome. Management of Kounis Syndrome relies upon addressing both cardiovascular aspects of the episode as well as allergic aspects.[xiv]

Costochondritis can occur in mast cell patients and may present as chest pain.

Mast cell patients may also have postural orthostatic tachycardia syndrome (POTS), a condition that can cause blood pressure and heart rate irregularities.[xii]

IV contrast poses significant to mast cell patients due to the high risk of systemic degranulation. If required, premedication is advised.[vi]

References:

[i] Douaiher J, et al. (2014). Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing. Adv Immunol, 122, 211-252.

[ii] Zhang D, et al. (2012). Mast-cell degranulation induced by physical stimuli involves the activation of transient receptor-potential channel TRPV2. Physiol Res, 61(1), 113-124.

[iii] Chatterjea D, Martinov T. (2015). Mast cells: versatile gatekeepers of pain. Mol Immunol, 63(1),38-44.

[iv] Dewachter P, et al. (2014). Perioperative management of patients with mastocytosis. Anesthesiology, 120, 753-759.

[v] Brockow K, Bonadonna P. (2012). Drug allergy in mast cell disease. Curr Opin Allergy Clin Immunol, 12, 354-360.

[vi] Molderings GJ, et al. (2016). Pharma,ological treatment options for mast cell activation disease. Naunyn-Schmiedeberg’s Arch Pharmol, 389:671.

[vii] Molderings GJ, et al. (2011). Mast cell activation disease: a concise, practical guide to diagnostic workup and therapeutic options. J Hematol Oncol, 4(10).

[viii] Carvalhosa AB, et al. (2015). A French national survey on clotting disorders in mastocytosis. Medicine (Baltimore), 94(40).

[ix] Peters EG, et al. (2015). The contribution of mast cells to postoperative ileus in experimental and clinical studies. Neurogastroenterol Motil, 27(6), 743-749.

[x] Biscotte SM, et al. (2007). Angiotensin II mediated activation of cardiac mast cells. The FASEB Journal, 21(6).

[xi] Kolck UW, et al. (2016). Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research, x, 1-10.

[xii] Shibao C, et al. (2005). Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension, 45, 385-390.

[xiii] Kennedy S, et al. (2013). Mast cells and vascular diseases. Pharmacology & Therapeutics, 138, 53-65.

[xiv] Kounis NG. (2016). Kounis Syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med, 54(10), 1545-1559.

[xv] Florea VG, Cohn JN. (2014). The autonomic nervous system and heart failure. Circulation Research, 114, 1815-1826.

[xvi] Morganstern JA, et al. (2008). Direct evidence of mast cell participation in acute acid-induced inflammation in mice. J Pediatr Gastroenterol Nutr, 46(2), 134-138.

[xvii] De Winter BY, et al. (2012). Intestinal mast cells in gut inflammation and motility disturbances. Biochimica et Biophysica Acta – Molecular Basis of Disease, 1822(1), 66-73.

[xviii] De Winter BY, et al. (2012). Intestinal mast cells in gut inflammation and motility disturbances. Biochimica et Biophysica Acta – Molecular Basis of Disease, 1822(1), 66-73.

[xix] Nurko S, Rosen R. (2010). Esophageal dysmotility in patients with eosinophilic esophagitis. Gastrointest Endosc Clin N Am, 18(1), 73-ix.

Gastroparesis: Post-surgical gastroparesis (Part Four)

Surgery is also a common trigger for gastroparesis.  GI surgery is often complicated by post-operative ileus, in which the GI tract is temporarily paralyzed, at least partially due to mast cell degranulation.  Gastroparesis is often viewed as analogous to post-op ileus, localized to the stomach.  In patients with post-op infections or organ failure, GP is also seen sometimes.  The gastric inflammation associated with surgery inhibits motility acutely.

A number of surgeries have been associated with GP, especially those that manipulate the stomach.  Partial or complete removal of the stomach (gastrectomy) can cause GP.  Removal of all or part of the pancreas also induces gastroparesis in about 20% of patients.  It is most often seen alongside other post-op complications.

(Author’s note: the previous paragraph originally had a sentence that said the following: “6.9% of patients who undergo radical gastrectomy develop GP.”  This is not correct and nonsensical, I made a mistake when typing this up.  I deleted the sentence from the above paragraph, and added a new sentence a few paragraphs down that says: “In a study with over 500 patients who underwent radical gastrectomy for gastric cancer, 6.9% of patients had gastroparesis.”  Sorry for any confusion I may have caused with this error.)

7.2% of all reported gastroparesis cases occurred following gastrectomy or fundoplication, operations that manipulate the stomach.  Fundoplication, which “wraps” the stomach around the esophagus to decrease reflux, can damage nerves and interfere with stomach relaxation.  If vagus nerve function is damaged, GP can result, often with a dominant bloating presentation.  Overall, Nissen fundoplication is the most common cause of post-surgical gastroparesis.  A follow up surgery to revert to a partial fundoplication with pyloroplasty (“loosening the wrap”) can sometimes reverse the gastroparesis.

Bariatric (weight loss) surgery carries the risk of upper GI dysfunction.  While this most often affects the esophagus, GP is sometimes seen, and it is usually very severe and persistent.  Botox injections and gastric electrical stimulation are sometimes fruitful in this population.

Gastroparesis can also result from a number of surgeries that do not directly manipulate the stomach.  Most of these surgeries could result in vagus nerve damage and therefore impact upper GI motility.  Removal of part of the esophagus, botox injections for achalasia, lung transplantation and liver surgeries can all cause gastroparesis.  Conditions that require gastric surgery can directly cause gastroparesis prior to surgical intervention.  In a study with over 500 patients who underwent radical gastrectomy for gastric cancer, 6.9% of patients had gastroparesis.

Conversely, stomach surgery can sometimes alleviate gastroparesis symptoms.  Subtotal or complete gastrectomy improves symptom profiles in 67% of patients.  In one small patient cohort, 6/7 patients having subtotal gastrectomy had immediate resolution of vomiting, with significant improvement in quality of life for up to six years.  Patients who have nausea as a cardinal symptom, who have previously needed TPN, or who have had retained food in the stomach during endoscopy, are less likely to have resolution due to these surgeries.  Post-op ileus, wound infection, intestinal obstruction and anastomotic leakage are common complications of these surgeries to mitigate gastroparesis.

References:

Sarosiek, Irene, et al. Surgical approaches to treatment of gastroparesis: Gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes.  Gastroenterol Clin N Am 44 (2015) 151-167.

Pasricha, Pankaj Jay, Parkman, Henry P. Gastroparesis: Definitions and Diagnosis. Gastroenterol Clin N Am 44 (2015) 1-7.

Parkman, H. P. Idiopathic Gastroparesis. Gastroenterol Clin N Am 44 (2015) 59-68.

Nguyen, Linda Anh, Snape Jr., William J. Clinical presentation and pathophysiology of gastroparesis.  Gastroenterol Clin N Am 44 (2015) 21-30.

Bharucha, Adil E. Epidemiology and natural history of gastroparesis. Gastroenterol Clin N Am 44 (2015) 9-19.

Camilleri, Michael, et al. Clinical guideline: Management of gastroparesis. Am J Gastroenterol 2013; 108: 18-37.

Gastroparesis: Treatment (part 2)

Initial management of gastroparesis often focuses on treating dehydration and electrolyte and nutritional deficits.  One study found that 64% of gastroparesis patients were not consuming enough daily calories to support the needs of their bodies, which can worsen symptoms.  Vitamins A, B6, C, and K, as well as iron, potassium and zinc are frequently deficient in this population.  Small meals low in fat and fiber are recommended for gastroparesis patients.  Liquids or blended solids often empty normally from the stomach.

For cases in which oral diet is unable to provide sufficient calories and nutrition, placement of a feeding tube may be necessary.  Jejunal feeding tubes are often used successfully.  Prior to surgical placement of a feeding tube, a nasojejunal tube should be used successfully.  PEG-J or Jet-PEG tubes allow venting of gastric secretions to reduce vomiting and nausea while providing a feeding route.

TPN (total parental nutrition) is given intravenously, but carries risks, including central line infections.  For patients in whom oral feeding is not feasible, a feeding tube is often considered the safer option.

Metoclopramide, a dopamine D2 receptor antagonist, is approved for treatment of gastroparesis.  However, treatment beyond 12 weeks should be considered only if the improvement on this medication is significant enough to outweigh risks.  Metoclopramide can cause dystonia and tardive dyskinesia.  Benzodiazepines and antihistamines are sometimes used to treat these side effects.  Domperidone is also a dopamine D2 receptor antagonist, but has lower incidence of side effects.  It is not approved in the US, but can be obtained via special FDA approval for US patients.

Medications to increase gastric motor activity, like erythromycin, are often used in gastoparesis patients.  When taken orally, erythromycin often becomes less effective after several weeks of relief.  Proton pump inhibitors and H2 antihistamines may provide some relief as gastroparesis is often associated with and irritating to GERD.

Medications for management of nausea and vomiting are mainstays for many gastroparesis patients, with phenothiazines or antihistamines often used for this purpose.  5-HT3 receptor antagonists like ondansetron are also widely used.  The neurokinin receptor-1 antagonist aprepitant is sometimes used after failing other antiemetics.  Scopolamine patches and dronabinol are also options.  Tricyclic antidepressants can be used to manage nausea, vomiting and abdominal pain, with nortriptyline and desipramine often preferred over amitriptyline, which can cause delayed emptying.  Mirtazapine has been reported as successful in a case study.

Abdominal pain associated with gastroparesis can be difficult to manage because opiates can induce gastroparesis.  Gabapentin, tramadol, tapentadol, pregabalin and nortriptyline are non-opiate options for pain management.

For some patients, more invasive treatment is indicated.  Some patients with gastroparesis have increased tone in the pyloric canal, which can contribute to delayed gastric emptying.  Injection of botulinum toxin (Botox) into the pyloric sphincter is sometimes tried.  In double-blind studies, use of Botox increases gastric emptying but does not improve symptom profiles.

There are surgical options to manage gastroparesis, with varying results.  Gastric electrical stimulation is considered for patients with long term symptoms that have not improved despite treatment.  These devices are implanted and provide low grade electrical stimulation to the stomach and increase motility.  In diabetic gastoparesis patients, this method improved quality of life and decreased symptoms.  Patients who acquired gastroparesis following surgery, or whose gastroparesis is idiopathic, were less likely to improve using GES.  Pyloroplasty and gastrectomy (partial or complete) have been trialed in some patients, but there is not a clear trend in the data.

Acupuncture has been shown to benefit gastroparesis patients in a number of studies, including one blinded, randomized study. Symptom severity was improved in those receiving acupuncture and gastric emptying time was decreased.  Autogenic retraining using the program developed by NASA for space motion sickness has shown some benefit.  Autogenic retraining was found to be more successful in patients with intact autonomic function.

References:

Sarosiek, Irene, et al. Surgical approaches to treatment of gastroparesis: Gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes.  Gastroenterol Clin N Am 44 (2015) 151-167.

Pasricha, Pankaj Jay, Parkman, Henry P. Gastroparesis: Definitions and Diagnosis. Gastroenterol Clin N Am 44 (2015) 1-7.

Parkman, H. P. Idiopathic Gastroparesis. Gastroenterol Clin N Am 44 (2015) 59-68.

Nguyen, Linda Anh, Snape Jr., William J. Clinical presentation and pathophysiology of gastroparesis.  Gastroenterol Clin N Am 44 (2015) 21-30.

Bharucha, Adil E. Epidemiology and natural history of gastroparesis. Gastroenterol Clin N Am 44 (2015) 9-19.

Camilleri, Michael, et al. Clinical guideline: Management of gastroparesis. Am J Gastroenterol 2013; 108: 18-37.

Gastroparesis: Part 1

Gastroparesis (GP) is a condition in which stomach contents are not emptied into the small intestine within an appropriate time period without an obvious anatomical explanation.  Gastroparesis patients are highly symptomatic, with approximately 90% reporting nausea, 84% vomiting, and abdominal pain, bloating, feeling unable to eat more after a small portion and feeling very “full” after even a small meal.  Some patients can manage their symptoms with dietary changes and medication, while others continue to be significantly symptomatic.

In some people, GP manifests episodically, with no symptoms for periods of time between flares.  In others, symptoms are chronic and perpetual.  Malnutrition, dehydration and weight loss can be severe in some cases.  Despite the primary functional feature of gastroparesis being the delayed emptying of the stomach, the degree to which gastric emptying is slowed correlates poorly with symptoms and severity of symptoms.

Gastroparesis affects at least 37.8 women/100000 persons and 9.6 men/100000 persons.  Once thought to be uncommon, it is now thought that gastroparesis may affect up to 2% of the population.  Hospital admissions for gastroparesis have increased dramatically in the last two decades, with a 158% increase between 1995 and 2004, with 138% of that increase occurring between 2000 and 2004.  There are several possible reasons for this phenomenon, including changes to criteria, better recognition and the withdrawal of cisapride from the market, a medication that alleviated some gastroparesis symptoms.

Gastroparesis is marked by generic gastrointestinal symptoms which can make it hard to identify unless the clinician is familiar with this condition.  Initially, it is often mistaken for functional dyspepsia.  For patients who have distinct episodes rather than continuous symptoms, patients are sometimes misdiagnosed with cyclic vomiting syndrome.

Gastroparesis can occur as a result of a number of diseases or circumstances.  Diabetes and surgery are the most commonly reported causes.  Idiopathic gastroparesis, in which no specific cause can be found, is often the most common in patient groups studied, with up to 1/3 of patients having this type.  Autonomic neuropathy, connective tissue diseases, autoimmune disease, thyroid disease can also cause gastroparesis, among many other conditions.

 

References:

Sarosiek, Irene, et al. Surgical approaches to treatment of gastroparesis: Gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes.  Gastroenterol Clin N Am 44 (2015) 151-167.

Pasricha, Pankaj Jay, Parkman, Henry P. Gastroparesis: Definitions and Diagnosis. Gastroenterol Clin N Am 44 (2015) 1-7.

Parkman, H. P. Idiopathic Gastroparesis. Gastroenterol Clin N Am 44 (2015) 59-68.

Nguyen, Linda Anh, Snape Jr., William J. Clinical presentation and pathophysiology of gastroparesis.  Gastroenterol Clin N Am 44 (2015) 21-30.

Bharucha, Adil E. Epidemiology and natural history of gastroparesis. Gastroenterol Clin N Am 44 (2015) 9-19.

Privilege

My body is changing. I am tired but do not sleep for twenty hours at a time. Bones and angles emerge as my swelling wanes. I exercise. I eat real food. I sleep at night.

At the same time, I am carefully engineering to encourage these continued changes. I still take a ton of medication. I still need IV fluids every day. I still need IV meds. I still need to manage my pain. I still need to be careful. This nethervoid I currently inhabit might never be mistaken for healthy, but it is healthy for me. It is stable at least, predictable. It is good for me.

Last week was composed of the oppressive, sticky summer days that Boston is known for. Heat, humidity and sunlight form my own personal triad of doom. I got halfway through my short walk between stations and started reacting badly. I went into a Starbucks and promptly threw up while hives appeared on my neck. All of my exposed skin was bright red. I took some Benadryl and drank some cold water and waited for things to calm down. They did. I continued on my way to work.

It is hard for me to gauge how bad I look on any given day, as I was for many years in a persistent reactive state. My only indication is that initial surprise when people look at me, that flash of concern as their eyes widen, a brief moment before they recover. I knew as soon as I got to work that I must look terrible.

We have a cold room at work that is essentially an enormous refrigerator. “Girl, you need to go stand in there,” one of my coworkers said with a supportive nod. So I did. It helped. When I emerged, multiple people told me they were worried I would anaphylax and to please take a cab home. I am so fortunate to work with this group of caring, wonderful people that understand my disease and want me to be safe.

I did end up taking a cab home. I didn’t want to, but I did. It’s hard for me to articulate why I didn’t want to, when I knew it was safer and easier, in a way that doesn’t make me sound crazy. Getting in that cab made me sad in this nebulous but palpable way.

Taking the train to work is a privilege. Going to work, cleaning your house, paying your bills, food shopping, making dinner, eating solids, crunching lettuce as you watch television, being part of the world. These are privileges. These are the things you miss when you are hospitalized or so tired that your whole body feels heavy or riding that knife’s edge of anaphylaxis because your body is fighting you on something you need to do.

All of the days you spend fighting – this is what it is for. You fight for these privileges. You fight to be in the world. These are the things you will miss. All you can ever hope for is to wake each day to a world full of mundane privileges.

Some days I want to take the train even if there is a chance I will get sick. Because there is a chance that I won’t. Once that was impossible. Maybe it will be again. Maybe tomorrow it will be impossible, but not today.

I am still sick. I am still in pain. I still have a poorly functioning GI tract. I still carry two Epipens and a backpack full of meds everywhere I go. I am still nauseous. After all of the effort put forth in the last three months, I did not get cured. I got to walk to work sometimes. I got to eat salad. I got to feel the sunlight on my skin. That’s what I got. And it’s enough, and even more than it’s enough, it’s amazing. All of this is amazing. I am alive this summer and I am alive in the heat and I am alive when I’m too hot and I’m alive in the sun.

You cannot always decide what you do, but you can always decide who you are. I cannot always walk in the summer sun, but I am always a person who wants to.

I choose to live in the world and to enjoy it and be alive. I choose this even when it might hurt me. I choose this even when it might kill me. It is where I want to be.

It is a privilege to participate in this world. It is a privilege to be alive.

Phantom

I have always been fascinated by both the human body and the diseases that affect it. When I was about ten years old, my parents bought me a medical dictionary. I read it cover to cover. I wrote little stories about people with Legionnaire’s Disease and Tetrology of Fallot, describing the symptoms and treatments in vivid detail.

It was in this dictionary that I first read about phantom pain. It always made a weird sort of sense to me. Bodies are creatures of habit, just like us. Of course your body expects to have all of the parts it started with. Of course your brain would assume it was merely misinterpreting signals when suddenly a limb was missing. The alternative was too awful to consider.

It never occurred to me that the body could experience phantom pain from a part of the body that was never supposed to exist. As soon as my epidural line was pulled five days post-op, I started having severe sporadic pain where my stoma used to be. It was distinct from the other pains – the burning in the lower colon, the sharpness in the rectum, the soreness near the incisions.

This was something different. It felt like when my body tried to pass stool through the stoma, but couldn’t because of an obstruction. It was the same exact same sensation. My body remembers the route of a path that should never have been there to begin with.

I lived 29 years without an ostomy. In the two years that I had it, I believed it was the best solution for me, and for most of that time, I believed that I would always have it. The only way to survive was a radical acceptance of this defect. I told myself that this was the best option for my body and I made myself believe it. I believed it so much that even my body was convinced.

I still have a wound where my stoma was. It is closing slowly. Mostly the pain is manageable; I know it will never really go away. Several times a day, I feel my body mimic the pressure of an obstruction behind the stoma, the twisting and lines of pain spiderwebbing into my lower back. The pain isn’t real, but my brain won’t believe it.

Phantom pain is notoriously resistant to pain medication. One of the better options is the use of psychological “tricks” to convince your body that it is still intact. I am thinking about how to do this. But I don’t know which version of my GI tract my brain thinks is real.

 

The high water mark

I spent most of the latter half of May in bed. People woke me up take medication on schedule and I fed myself small meals periodically. I watched movies and TV and drifted in and out of sleep, pain killers and Benadryl making the world soft around the edges.

Every day, even as I felt myself healing, my strength and stamina waned. My legs felt weak when I stood up. I got winded walking around the block. Holding my head up felt difficult. All of the stamina I had built up before surgery was gone. All of my progress was undone.

I spend so much energy trying to get somewhere I’m never going to get – to this place of physical health where I can exercise and sleep at night and wake in the morning without bleary eyes and a pounding headache. I have been trying to reach this milestone since well before I knew I was sick.

I’m not even sure I know the closest I ever came. What is the highwater mark of this particular struggle? Was it the few weeks before my last birthday when I was sleeping at night and waking without an alarm? Or that really good day last September? The few weeks after my colostomy healed? I don’t know. I’m not sure there is a high water mark. Everything is relative.

Living with a sickness that causes regular setbacks – and requires treatments that sometimes do the same – is difficult. This halting start has become a sort of rhythm, the timing an inherent part of this experience. I’m never getting anywhere. I’m always getting it wrong. It feels like if I could do the right things in the right order that it would make a difference. `

But what if every time I started again, it didn’t mean that every time before was a failure? All those times before, all the moves in the wrong order, kept me alive and participating in the world. How wrong could they be? What if the high water mark of this struggle is just being alive?

Reversing the ostomy was the right move. I am noticeably less inflamed and my body is responding. I am having fewer reactions. I am eating without vomiting. The squishiness, the swelling weight is melting away so I can see the features beneath. I am still in pain, but I think I always will be.

I’m getting stronger. It’s slow, but it’s happening. I can walk for twenty minutes now, Astoria happily padding along beside me. I’m short of breath and sweaty when I’m done, but I can do it.

Maybe it’s time to stop blaming myself for all the times I had to start over. Maybe it’s time to see these setbacks as opportunities to understand my body and learn from it.

Maybe this is enough.