Reintroduction of food to a child with SM

I recently put together some recommendations on reintroducing foods to a child with SM who has been exclusively on IV nutrition (TPN) for an extended period of time. I thought you might find some use in it so I have posted it here.

Before people ask, there are no significant publications on children with MCAS because there are not currently unifying diagnostic criteria.

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Author’s note: I am not a medical doctor. Protocols for reintroducing foods must be developed by the managing care team and tailored to each patient.

There are no large population studies for pediatric systemic mastocytosis. True systemic mastocytosis (in which WHO diagnostic criteria are satisfied) is rare in children. Accordingly, SM in children is generally reported as case reports rather than studies given the population size[i].

Given the lack of in depth literature specifically regarding food challenge in children with SM, I would draw from data in similar situations to identify a safe and appropriate protocol for reintroducing for [name redacted].

There are five scenarios that may contribute insight for food reintroduction in this patient: oral food challenges for FPIES patients; desensitization procedures for delayed hypersensitivity reactions; reintroduction of food after long term parenteral therapy; premedication of patients with mast cell activation disease, including systemic mastocytosis; and mast cell involvement in gastroparesis, ileus and GI dysmotility.

Based upon these scenarios, we can infer the following:

  • Reintroduction of food to this patient should follow a long, repetitive schedule with gradually increasing quantities.
  • Premedication with antihistamines and glucocorticoids to avoid mast cell reaction should be considered.
  • Mast cell activation can directly induce GI dysmotility. Drug management of mast cell activation can suppress impact upon function.
  • Enteral feeds should be gradually increased while parenteral feeds are gradually decreased.
Scenario Application to food reintroduction in a mast cell patient
1 Oral food challenge in setting of FPIES FPIES and food reactions secondary to mast cell disease are both non-IgE mediated and can culminate in shock requiring emergency intervention.
2 Desensitization for delayed drug hypersensitivity reactions Mast cell degranulation and anaphylactic reactions are not type I hypersensitivity reactions. They may also present on a delayed schedule.
3 Reintroduction of food after long term parenteral nutrition Reintroducing food to patients after long term parenteral nutrition may impact GI function. Gradual reintroduction is recommended.
4 Premedication of patients with mast cell activation disease Patients with mast cell activation disease, including systemic mastocytosis, are advised to premedicate prior to all procedures to decrease risk of reaction and anaphylaxis.
5 Mast cell involvement in gastroparesis, ileus, and GI dysmotility Mast cells contribute significantly to GI motility disorders including gastroparesis and ileus.

 

  1. Oral food challenge in patients with food protein induced enterocolitis syndrome (Caubet 2014[ii], Leonard 2011[iii])
  • Food protein induced enterocolitis syndrome (FPIES) is a severe non –IgE mediated GI food hypersensitivity syndrome.  Patients with FPIES are children. The condition is managed by removing the offending food from the diet for extended periods, usually years.
  • Food challenge in FPIES can result in severe, repetitive vomiting; diarrhea; lethargy; pallor; hypothermia; abdominal distension; and low blood pressure. Not all of these features are universally present for all patients.
  • The following procedure is recommended for oral food challenge in FPIES children:
  • All FPIES oral food challenges must be physician supervised with appropriate supportive care available.
  • Over the first hour, 0.06-0.6 g/kg body weight of food protein should be administered in three equal doses. It should not exceed 3g of total protein or 10g of total food or 100ml of liquid for initial feeding.
  • If patient has no reaction, give a full serving of food as determined by their age.
  • Observe patient for several hours afterward.
  • In the event of severe reaction, administer 1mg/kg methylprednisolone intravenously, up to 60-80 mg total; 20 ml/kg boluses of NS; and epinephrine.
  • Food challenge is considered positive for reaction if patient experiences typical symptoms as a direct result of the challenge.

 

  1. Desensitization for delayed hypersensitivity medication reactions (Scherer 2014[iv], Leoung 2001[v])
  • There are no controlled studies available on desensitization for delayed reactions to drugs.
  • Described procedures have timespans ranging from hours to weeks.
  • Patients who initially failed rapid protocols have succeeded using slower procedures.
  • It may take 2-3 days before hypersensitivity symptoms develop in a delayed reaction.
  • Long protocols with repetitive, gradually escalating dosing are recommended.
  • Antihistamine prophylaxis is often recommended. Drug and dosing vary.
  • The following procedure describes an example of a gradually escalating dosing:

Dose escalation for desensitization, adapted from antibiotic desensitization procedure

(Leoung 2001)[v]

Dosing level Drug portion Frequency of daily dosing
1 12.5% QD
2 25% BID
3 37.5% TID
4 50% BID
5 75% TID
6 100% QD

 

  1. Reintroduction of food after long term parenteral nutrition (Hartl 2009[vi], Oley Foundation)
  • Long term TPN may increase intestinal permeability.
  • Long term TPN may result in diminished enzymatic activity in GI mucosa.
  • The Oley Foundation suggests decreasing parenteral nutrition by 25% while increasing enteral feeds by 25% as the patient tolerates.

 

  1. Premedication of patients with mast cell activation disease (Castells 2016[vii])
  • Mast cell patients are recommended to premedicate for all procedures using H1 and H2 antihistamines, glucocorticoids, and leukotriene receptor antagonists.

 

  1. Mast cell involvement in gastroparesis, ileus, and GI dysmotility (Nguyen 2015[viii], de Winter 2012[ix])
  • Mast cells can be activated by a number of pathways which do not involve IgE, including neuropeptides, complement factors, cytokines and hormones.
  • Mast cells in the GI tract are closely associated with afferent nerve endings.
  • Mast cell behavior in the GI tract is largely controlled by the central nervous system.
  • Mast cells are directly involved in GI dysmotility disorders including gastroparesis and ileus.
  • Mast cell activation and population may be upregulated in the setting of GI inflammation.

[i] Lange M, et al. (2012) Mastocytosis in children and adults: clinical disease heterogeneity. Arch med Sci, 8(3): 533-541.

[ii] Caubet JC, et al. (2014) Clinical features and resolution of food protein induced enterocolitis syndrome: 10-year experience. J Allergy Clin Immunol, 134(2): 382-389.

[iii] Leonard S, et al. (2011) Food protein induced enterocolitis syndrome: an update on natural history and review of management. Ann Allergy Asthma Immunol, 107:95-101.

[iv] Scherer K, et al. (2013) Desensitization in delayed drug hypersensitivity reactions – an EAACI position paper of the Drug Allergy Interest Group. European Journal of Allergy and Clinical Immunology, 68(7): 844-852.

[v] Leoung GS, et al. (2011) Trimethoprim-sulfamethoxazole (TMP-SMZ) Dose Escalation versus direct rechallenge for Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus-infected patients with previous adverse reaction to TMP-SMZ. Journal of Infectious Diseases, 184:992-997.

[vi] Hartl WH, et al. (2009) Complications and monitoring – Guidelines on Parenteral Nutrition, Chapter 11. Gen Med Sci, 7:Doc17.

[vii] http://www.tmsforacure.org/documents/ER_Protocol.pdf

[viii] Nguyen LA, et al. (2015) Clinical presentation and pathophysiology of gastroparesis. Gastroenterol Clin N Am, 44: 21-30.

[ix] de Winter BY, et al. (2012) Intestinal mast cells in gut inflammation and motility disturbances. Biochimica et Biophysica Act, 1822: 66-73.

Take home points: August 2015

Gastroparesis: Part 1

  • GP is a condition in which stomach contents do not move into the small intestine in an appropriate time frame without an obvious anatomical reason
  • GP patients can have severe symptoms, including nausea, vomiting, abdominal pain and bloating
  • GP can be episodic or chronic
  • The degree of gastric emptying delay does not impact symptom severity
  • GP may affect up to 2% of the population
  • GP is increasing over the last twenty years with no clear reason as to why
  • Cisapride is effective for treating GP but was removed from the market
  • GP symptoms are generic and make the cause hard to identify
  • Idiopathic GP has no clear cause and affects up to 1/3 of GP patients

Gastroparesis: Treatment (Part 2)

  • Treating dehydration and electrolyte and nutritional deficiencies are key to initial GP management
  • 64% of GP patients do not consume enough daily calories
  • Vitamins A, B6, C and K, iron, potassium and zinc are often deficient in GP patients
  • Small meals with low fat and fiber are recommended
  • Liquids or blended solids often empty normally from stomach
  • Feeding tubes may be placed if malnutrition is significant
  • Metoclopramide is approved for GP but use longer than twelve weeks carries risks like dystonia
  • Domperidone is not approved in US for GP but can be imported through a special FDA program for GP
  • Medications to increase gastric motility, like erythromycin, are often used
  • Medications for nausea and vomiting are common, such as ondansetron, scopolamine, draonabinol and tricyclic antidepressions
  • Nortriptyline and desipramine are tricyclics of choice as amitryptline can cause delayed gastric emptying
  • Opiates can induce GP so meds like gabapentin, tramadol, tapentadol, pregabalin and nortriptyline are preferred for abdominal pain
  • Botox injection into pyloric sphincter can increase gastric emptying but doesn’t always improve symptoms
  • Acupuncture and gastric pacemaker are also options

Gastroparesis: Diabetes and gastroparesis (Part 3)

  • 40% of patients with type I diabetes have delayed gastric emptying
  • 20% of patients with type II diabetes have delayed gastric emptying
  • In 2004, 26.7% of GP patients had diabetes
  • Diabetic patients with GP are more likely to have nausa and vomiting as predominant symptoms
  • GP can hinder effective blood sugar management
  • High blood sugar is associated with GP and vagus nerve damage
  • Gastric electric stimulation (gastric pacemaker) works better when GP is caused by diabetes than GP from other causes
  • Effective GP management improves blood sugar management and A1C level

Gastroparesis: Post-surgical gastroparesis (Part Four)

  • Surgery is a common trigger for GP
  • Surgeries that manipulate the stomach are more associated with GP, like gastrectomy, fundoplication or weight loss surgery
  • Gastric inflammation associated with surgery inhibits GI motility
  • 7.2% of GP cases occur after gastrectomy or fundoplication
  • Nissen fundoplication is the most common cause of post-surgical GP
  • A follow up surgery after Nissen fundoplication can sometimes reverse GP
  • Surgeries that don’t manipulate the stomach can also cause GP, like removal of esophagus, lung transplant, and liver surgery

Gastroparesis: Less common causes (Part Five)

  • Parkinson disease, multiple sclerosis, muscular dystrophy, myopathy, scleroderma, Sjogrens, polymyositis and stroke can all cause GP.
  • 10.8% of GP cases are associated with connective tissue disorder
  • Pseudo obstruction syndromes and autonomic neuropathy can occur concurrently with GP
  • Viral infections can cause acute GP that usually resolves within a year
  • Spinal cord injury, hypothyroidism, hyperparathyroidism, Addison’s disease and use of opiates or anticholinergics can contribute to GP
  • GP occurs disproportionately in people who have had their gallbladders removed
    • Often, GP does not immediately follow gallbladder removal but can present months or years later
    • Gallbladder removal is also associated with conditions that can occur with GP such as chronic fatigue syndrome, fibromyalgia, depression and anxiety
    • GP patients who have had gallbladders removed are usually older women who are overweight despite not coming enough calories

Take home points: September 2015

Naturally occurring mast cell stabilizers: Part 1

Naturally occurring mast cell stabilizers: Part 2

Naturally occurring mast cell stabilizers: Part 3

Naturally occurring mast cell stabilizers: Part 4

Amentoflavone Ginkgo biloba, St. John’s Wort Decreases histamine release
Artekeiskeanol A Artemisa keiskeana May treat arthritis

Decreases mast cell degranulation

Decreases production of IL-13 and TNF

Curcimin Turmeric Decreases degranulation

Decreases production of IL-4 and TNF

Ellagic acid Strawberries, raspberries, pomegranate, walnuts Suppresses IgE activation

Decreases release of histamine, TNF, IL-6

Emodin Rhubarb, frangula bark Decreases IgE degranulation

Decreases IgE triggered production of TNF, PGD2, LTC4

Decreases secretion of TNF and IL-6

Epigallocatechin gallate White and green teas, apples, onions, hazelnuts Decreases degranulation

Decreases LTC4 secretion

Fisetin Apples, onions, persimmon, strawberries, cucumber Decreases IgE degranulation

Decreased IgE triggered histamine release

Decreases production of IL-1b, IL-6, IL-8 and TNF

Decreased action of NF-kB, decreased mediator production

Furanocoumarin from Angelica dahurica Angelica dahurica Inhibits COX-2 and 5-LO, decreasing production of prostaglandins and LTC4
Genistein Genista tinctoria Decreases IgE degranulation

Decreases histamine release

Nature tyrosine kinase inhibitor

Ginkgetin Gingko biloba Inhibits COX-2 and 5-LO, inhibiting production of prostaglandins and leukotrienes
Gnetin H Paeonia aneomala Resveratrol derived polymer

Decreases mast cell degranulation

Effective at lower dose than reservatrol

Decreases histamine secretion

Decreases production of TNF, IL-4, COX-2 and PGE2

Homoisoflavonone Cremastra appendiculata Inhibits COX-2 and 5-LO, inhibiting production of prostaglandins and leukotrienes

Decreases IgE triggered production of TNF and IL-6

Honokiol Magnolia obovata Suppresses allergic response and basophil activation
Hydroxytyrosol Olive oil, olive leaves Inhibited activation of mast cells at high concentration
Hypothemycin Hypomyces mushrooms Interfere with activation of CKIT and IgE receptors, inhibiting mast cell activation

 

Decreases production of IL-4

Kaempferol Potatoes, squash, cucumbers, peaches, Aloe versa Decreases IgE degranulation

Decreased IgE triggered histamine release

Affects estrogen signaling

Luteolin Celery, carrots, chamomile tea Prophylactic use of luteolin suppresses activation of mast cells and T cells

Decreases IgE degranulation

Decreases production of mediators

Magnolol Magnolia obovata Suppresses allergic response and basophil activation
Morin Osage orange, guava Decreases mast cell degranulation

Decreases IgE activation

Myricetin Walnuts, onions, red grapes Decreases IgE degranulation

Decreased IgE triggered histamine release

Decreases production of IL-6 and TNF

Decreased action of NF-kB, decreased mediator production

Polydatin Resveratrol precursor

Makes small intestine mucosa less “leaky” and inhibited allergic reaction in intestines

Decreases degranulation by up to 65%

Decreases histamine in intestinal mucosa and serum

Decreases production of IL-4

Quercetin Red onion, sweet potato, kale Inhibits production of histamine, prostaglandins, leukotrienes, IL-1b, IL-6, IL-8 and TNF
Resveratrol Grapes, raspberries, blueberries, peanuts Directly interferes with degranulation

Decreases production of TNF, IL-6 and IL-8

Rottlerin Mallotus philippensis Decreases degranulation of airway mast cells

Decreases histamine release

Suppresses IgE activation

Rutin Decreases IgE degranulation

Decreased IgE triggered histamine release

Decreases production of IL-1b, IL-6, IL-8 and TNF

Decreased action of NF-kB, decreased mediator production

Scopoletin Stinging nettle, Japanese belladonna, chicory, passion flower Decreases production of TNF, IL-6, IL-8

Inhibits NF-kB, affecting mediator production

Selinidin Angelia keiskei Inhibits IgE degranulation

Decreases production of LTC4 and TNF

Substance Source Function
Thunberginol A Hydrangeae macrophylla Decreases histamine release

Decreases production of TNF and IL-4

Thunberginol B Hydrangeae macrophylla Decreases degranulation from IgE or other sources

Decreases IgE triggered production of IL-2, IL-3, IL-4, IL-13, TNF and GM-CSF

Xanthones from purple mangosteen Garcinia mangostana Decreases release of histamine, PGD2, LTC4 and IL-6

 

Role of sex hormones in hereditary angioedema

Gastroparesis: Autonomic nervous system and vagus nerve (Part Six)

  • ANS controls many involuntary functions including digestion and therefore gastric emptying
  • The vagus nerve coordinates gastric motility
  • ANS dysfunction inhibits digestion and motility
  • GP is common in patients with ANS conditions, like POTS
  • Treatment of autonomic dysfunction (as in POTS) can sometimes improve GP
  • Damage to the vagus nerve can cause liquids to move rapidly out of the stomach while solids are retained
  • Surgery and high blood sugar can damage the vagus nerve
  • In GP patients, nerve cells are not shaped correctly
  • 83% of GP patients have abnormalities in their stomach biopsies

Gastroparesis: Idiopathic gastroparesis (Part Seven)

  • 35-67% of GP cases are idiopathic (IGP)
  • IGP affects three times more women than men, especially young and middle-aged women
  • IGP is more likely in young women who are overweight or obese
  • Moderate to severe abdominal pain was more frequent in IGP than other types
  • Nausea, abdominal pain, vomiting, bloating and feeling full are common in IGP
  • Medications that may be helpful but need investigation include sildenafil, paroxetine, cisapride, tegaserod, clonidine and buspirone

Gastroparesis: Idiopathic gastroparesis (Part Seven)

Gastroparesis occurring in the absence of any known trigger, such as diabetes, surgery, medication or disease related onset, is classified as idiopathic gastroparesis.  In most series that include patients with multiple forms of gastroparesis, idiopathic gastroparesis (IGP) is the most common, affecting 35-67% of GP cases.  As with most forms of GP, IGP affects about three times more women than men, particularly young and middle-aged women.  IGP in particular affects young women who are overweight or obese.

In a study including 243 patients with IGP, 88% were female.  34% reported frequent nausea, 23% abdominal pain and 19% vomiting.  28% had severely delayed gastric emptying, here defined as more than 35% retention of contents four hours after consumption.  46% were overweight.  When compared to patients with diabetic GP, IGP patients more often reported feeling too full after eating and that their hunger was sated by smaller meals.  IGP patients demonstrated more severe gastric retention than type I diabetic GP patients.

Moderate/severe upper abdominal pain was found to be more frequent in IGP, and correlated with GP severity, decrease in quality of life, depression and anxiety.  Having pain as the predominant symptom causes quality of life impairment equivalent with nausea and vomiting.

Bloating is a common GP symptom.  Severe bloating was present in 41% of patients, and was more common in overweight female patients.  It also corresponded with severe nausea, fullness, distention, abdominal pain and notable bowel dysfunction.  Quality of life and other measures of wellbeing decrease as bloating becomes more severe.

Idiopathic GP is treated similarly to other types, but diagnosis may be delayed due to the lack of a known trigger.  Medications that have been reported as helpful but have not been studied in larger populations include sildenafil, paroxetine, cisapride, tegaserod, clonidine and buspirone.

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: Autonomic nervous system and vagus nerve (Part Six)

Gastric emptying is facilitated by neurologic signals through the autonomic nervous system.  The autonomic nervous system controls many of the involuntary functions of the body, such as digestion.  The autonomic nervous system has two components: the parasympathetic nervous system, which manages activities pertaining to digestion, among other things; and the sympathetic nervous system, which mediates the fight-or-flight response.  Normally, upper GI function receives parasympathetic neurologic signals from the vagus nerve.  Sympathetic control is maintained by nerves originating at spinal T5-T10.

The vagus nerve sends signals the enteric neurons, nerve cells in the GI tract, to increase gastric motility.  The vagus nerve does not directly stimulate smooth muscle in the GI tract.  Signals from the vagus nerve help to relax the stomach to allow room for food, contract to move the food to the pyloric sphincter, and relax the pyloric sphincter to pass stomach contents to the small intestine.  These actions occur by coordinating the signals among the enteric neurons (GI nerve cells), interstitial cells of Cajal (which control smooth muscle contraction) and smooth muscle cells.

Normally, food passes through the esophagus and into the portion of the stomach closest to the esophagus.  The pressure of the food in this area causes other parts of the stomach to relax and allow food.  The stomach then contracts to break up food and push it towards the small intestine.

At any part of this process, dysfunction of the autonomic nervous system can inhibit proper digestion and gastric emptying.  Gastroparesis is a frequent complication of conditions affecting autonomic function, like orthostatic intolerance.  In some cases, treatment of the orthostatic intolerance can improve gastroparesis symptoms.

Vagotomy, an outmoded surgical treatment for ulcers that severs the vagus nerve, prevents the stomach from being able to relax to accept food.  It can trigger rapid movement of liquids through the stomach, while not allowing solids to be emptied.   Unintentional damage to the vagus nerve can be occur for a number of other reasons, including surgery or persistent high blood sugar, as in some diabetics.

The tone of the stomach and how much food can fit is controlled by enteric nerve cells that release nitric oxide (NO.)  NO keeps the stomach relaxed.  Interfering with cholinergic signaling can also keep the stomach relaxed, to fit more food.  Medications like opiates and anticholinergics have this effect.

In GP patients, stomach biopsies show that the enteric neurons are not shaped correctly. There are far fewer interstitial cells of Cajal than normal, and those that remain look damaged.  There are less nerve fibers than normal.  83% of GP patients have abnormalities in their stomach biopsies.

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: Less common causes (Part Five)

A number of other conditions can cause GP less frequently.  Parkinson disease is well known to cause GI motility issues, including GP.  In this group, the GI dysfunction is due to poor control of the smooth muscle in the GI tract.  Multiple sclerosis, muscular dystrophy, myopathy and having a stroke can negative impact gastric emptying.  50-75% of scleroderma patients with GI symptoms have delayed emptying.  29% of Sjogrens patients have GP.  GP is also sometimes present in polymyositis cases.

10.8% of GP cases are associated with some type of connective tissue disorder.  A clear connection to hypermobility type EDS is being elucidated.  Pseudoobstruction syndromes are sometimes comorbid with GP.  A significant number of patients affected by conditions that feature autonomic neuropathy have GP.

Some viral infections can cause acute GP, which generally resolves within a year.  Spinal cord injury, hypothyroidism, hyperparathyroidism, Addison’s disease, and regular use of opiates and/or anticholinergic medications can also contribute.

While the reason for this link is unknown, gastroparesis occurs disproportionately in patients who have had their gallbladders removed.  In many patients, the gastroparesis does not immediately follow gallbladder removal surgery – it can sometimes take years to present.  Prior gallbladder removal can worsen diabetic or idiopathic GP.  Gallbladder removal (cholecystectomy) is associated with several conditions that can be comorbid with gastroparesis, including chronic fatigue syndrome (CFS), fibromyalgia, depression and anxiety.  Severe upper abdominal pain and retching are cardinal GP symptoms in this population, with nausea and constipation less severe.

GP patients who previously had their gallbladders removed are frequently older women who are overweight despite not consuming enough calories.  Overweight people with GP are more likely to have severe bloating.  Significant bloating indicates poor response to management.  Medications that increase reuptake of norepinephrine, such as tricyclic antidepressants, can help manage bloating in some patients.

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: 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: Diabetes and gastroparesis (Part 3)

Diabetes is one of the most common causes of gastroparesis. 40% of patients with long term diabetes mellitus type I and 20% with diabetes mellitus type II have delayed gastric emptying.   In 1995, 21% patient of gastroparesis patients had DM; in 2004, 26.7%.

Diabetes patients are more likely to have nausea and vomiting as the cardinal GP symptoms, rather than epigastric pain seen more frequently in idiopathic GP.  `Diabetic GP is known to cause more severe gastric retention than idiopathic GP.

Diabetic patients with gastroparesis are at risk for developing difficulty in managing sugar levels.  Poor control of blood sugar can contribute to delayed gastric emptying.  Hyperglycemia is associated with decreased movement of the stomach, an effect more pronounced above 250 mg/dL.  Additionally, some medications used for diabetes, like exenatide for type II diabetes, can delay gastric emptying.  Persistent hyperglycemia is often cited as contributing to vagus nerve damage, which can also result in GP.

In one series, 58% of DM patients had increased tone in the pyloric sphincter, through which food passes from the stomach into the small intestine.  Pyloric tone is often elevated in GP patients.  Botox injections into the pyloric sphincter has been associated with increased gastric emptying and relief of symptoms in diabetic GP patients.

Gastric electric stimulation is more likely to be successful in diabetic patients versus those whose GP is not associated with diabetes, showing 50% reduction in symptoms over those with idiopathic GP.  Patients also experience better glycemic control when GP is more controlled, as reflected by reduction in hemoglobin A1C.

Gastroparesis in diabetes patients is well studied.  Curiously, improving glycemic control is not associated with symptom improvement (or change at all) in patients with type II diabetes.  In type I diabetics, symptom change has only correlated well with depression.

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.