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.

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

 

Symptom Cough
Role of mast cells Several mast cell mediators contribute to airway inflammation and subsequent symptoms including cough:

•             Histamine promotes bronchoconstriction, excessive production of mucus, and airway edema.[i]

•             Prostaglandin D2 promotes bronchoconstriction, mucus production, and airway edema.[i]

•             Leukotrienes C4 and D4 and chymase also contribute to mucus production and airway edema.[i]

•             Tryptase promotes overall increased reactivity of the airway.[i]

Chronic airway inflammation, as in asthma, is sometimes associated with increased mast cell population in pulmonary tissues.[i]

Mast cells remain activated in inflamed airways.[i]

Impact of condition on mast cells Mast cell activation can occur as a result of the physical stimuli such as coughing[ii].

Pain can trigger mast cell activation[iii].

Notes regarding condition treatment Dextromethorphan can trigger mast cell degranulation[iv].

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

Beta-2 adrenergic agonists, inhaled and oral steroids, and inhaled cromolyn are frequently used in mast cell patients[vi].

Notes regarding mast cell treatment Antihistamines, leukotriene receptor antagonists, and COX inhibitors are routinely taken by mast cell patients and can provide relief.[vii]

Racemic epinephrine can provide relief of pulmonary symptoms.[viii]

Special considerations for mast cell patients Chronic dry, unproductive cough sometimes occurs in mast cell patients.[ix]

Mast cell patients frequently have reactive airways.[ix]

Mast cells can produce and release prostaglandin E2, a mediator that participates in asthmatic inflammation and cough[x].

Prostaglandin E2 can also downregulate or promote mast cell degranulation via binding at prostaglandin E2 receptors on mast cell surface[x].

 

Symptom Sore throat
Role of mast cells Pain can trigger mast cell activation.[iii]
Impact of condition on mast cells Mast cell driven nasal congestion can result in postnasal drip can irritate the throat.[ix]

Mast cell irritation of the throat can present similarly to infection by Streptococcus spp. or other pathogen. Cultures should be taken to properly evaluate for infection.[ix]

Viral, bacterial and fungal infection will activate mast cells through toll like receptors and through perpetuated inflammatory signaling.[xiii]

Notes regarding condition treatment Acetaminophen is recommended for pain relief in mast cell patients.[iv]
Notes regarding mast cell treatment Antihistamines and COX inhibitors are routinely taken by mast cell patients and can provide relief.[vi]
Special considerations for mast cell patients Angioedema of the throat driven by mast cell disease is always a consideration in mast cell patients. If angioedema secondary to mast cell disease impinges upon airway, epinephrine and subsequent anaphylaxis treatments should be undertaken.[vii]

Oral allergy syndrome should be considered.[ix]

 

Symptom Rash
Role of mast cells Acute urticaria is usually driven by mast cell and basophil activation through IgE or non-IgE pathways.[xi]

Mast cell mediators histamine, leukotrienes and platelet activating factor contribute to itching.[xii]

Impact of condition on mast cells Viral, bacterial and fungal infection will activate mast cells via toll like receptors and perpetuated inflammatory signaling.[xiii]

Non-mast cell driven conditions causing skin rashes can irritate mast cells in the skin.[xii]

Pain can trigger mast cell activation.[iii]

Notes regarding condition treatment Some -azole antifungals can induce mast cell degranulation.[xiv]
Notes regarding mast cell treatment Antihistamines and steroids, topical or systemic, and topical cromolyn can provide relief.[xii]
Special considerations for mast cell patients Mediator release by activated mast cells can produce systemic symptoms.[x]

In patients with a history of mast cell disease, mastocytosis in the skin should be considered.

o             Cutaneous mastocytosis accounts for approximately 90% of mastocytosis cases.[xii]

o             Cutaneous mastocytosis lesions demonstrate Darier’s sign, a wheal and flare reaction to touch.[xii]

o             A skin biopsy is necessary to confirm a diagnosis of cutaneous mastocytosis.[xii]

o             Patients with adult onset cutaneous mast cell lesions are usually later found to have systemic mastocytosis.[xii]

 

Symptom Fever
Role of mast cells Mast cells can produce prostaglandin E2.[x]

Mast cells can produce and release several pyrogens, including IL-1α, IL-1β, IL-6, IL-8, TNF, interferon-α, interferon-β, and interferon-γ.[x]

Impact of condition on mast cells Prostaglandin E2 can also downregulate or promote mast cell degranulation via binding at prostaglandin E2 receptors on mast cell surface.[x]

Pain can trigger mast cell activation.[iii]

Viral, bacterial and fungal infection will activate mast cells via toll like receptors and perpetuated inflammatory signaling.[xiii]

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

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

Notes regarding mast cell treatment COX inhibitors are routinely taken by mast cell patients and may provide relief.[vi]
Special considerations for mast cell patients

 

Symptom Earache
Role of mast cells Mast cells are involved in the transmission of pain stimuli, including nerve pain.[iii]

Mast cells are involved in sensorineural hearing loss and tinnitus.[ix]

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

Viral, bacterial and fungal infection will activate mast cells via toll like receptors and perpetuated inflammatory signaling.[xiii]

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

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

Steroids (local and systemic) can stabilize mast cells.[vi]

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

Antihistamines can provide relief for vestibular symptoms.[vi]

Special considerations for mast cell patients Hearing loss, tinnitus and hyperacusis sometimes occur in mast cell patients.[ix]

Sensorineural hearing loss of unknown origin has been documented in mast cell patients.[ix]

Some mast cell patients also have Ehlers Danlos Syndrome which can cause conductive hearing loss.[ix]

Mast cell disease can also cause auditory processing disorder.[ix]

Red ears are a common sign of mast cell activation. Sometimes, only one ear is affected.[ix]

 

Symptom Stomachache
Role of mast cells Mast cells are commonly found in the GI tract.[xvi]

Mast cell activation is involved in a number of GI conditions, including inflammatory bowel disease, ulcerative colitis and food allergies.[xvi]

Mast cell activation can cause chronic diarrhea, pseudoobstruction, obstruction, dysmotility, constipation, nausea, vomiting, and visceral GI pain.[xvi]

Impact of condition on mast cells GI inflammation can recruit mast cells to inflamed tissues.[xvi]

GI inflammation can trigger mast cell mediator release.[xvi]

Pain can trigger mast cell activation.[iii]

Viral, bacterial and fungal infection will activate mast cells via toll like receptors and perpetuated inflammatory signaling.[xiii]

Notes regarding condition treatment
Notes regarding mast cell treatment Histamine H2 blockers and PPIs are commonly taken by mast cell patients and can provide relief.[vi]
Special considerations for mast cell patients Mast cell patients can experience a wide array of severe GI symptoms with or without dense infiltration of GI tract by mast cells.[ix]

 

[i] Cruse G, Bradding P. (2016). Mast cells in airway diseases and interstitial lung disease. European Journal of Pharmacology 778, 125-138.

[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). Pharmacological treatment options for mast cell activation disease. Naunyn-Schmiedeberg’s Arch Pharmol, 389:671.

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

[viii] Walsh P, et al. (2008). Comparison of nebulized epinephrine to albuterol in bronchiolitis. Acad Emerg Med, 15(4):305-313.

[ix] Afrin LB. (2013). Diagnosis, presentation and management of mast cell activation syndrome. Mast cells.

[x] Theoharides TC, et al. (2012). Mast cells and inflammation. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 1822(1), 21-33.

[xi] Bernstein JA, et al. (2014). The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol, 133(5):1270-1277.

[xii] Hartmann K, et al. (2016). Cutaneous manifestations in patients with mastocytosis: consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma and Immunology; and the European Academy of Allergology and Clinical Immunology. Journal of Allergy and Clinical Immunology, 137(1):35-45.

[xiii] Sandig H, Bulfone-Paul S. (2012). TLR signaling in mast cells: common and unique features. Front Immunol, 3;185.

[xiv] Toyoguchi T, et al. (2000). Histamine release induced by antimicrobial agents and effects of antimicrobial agents on vancomycin-induced histamine release from rat peritoneal mast cells.  Pharm Pharmacol, 52(3), 327-331.

[xv] Grosman N. (2007). Comparison of the influence of NSAIDs with different COX-selectivity on histamine release from mast cells isolated from naïve and sensitized rats. International Immunopharmacology, 7(4), 532-540.

[xvi] Ramsay DB, et al. (2010). Mast cells in gastrointestinal disease. Gastroenterology & Hepatology, 6(12): 772-777.

 

The Devil’s Arithmetic

When I was in grad school, I took immunology. I still have my textbook and refer to it sometimes, my crowded notes in the margins. The chapter on allergy and anaphylaxis is highlighted in green, somehow aggressively bright after eleven years.

It’s kind of amusing to recall this time in my life, before every mast cell activation pathway had been hammered into my brain. There’s also some black humor in reading about how IgE activation is the allergy pathway. You know, THE allergy pathway. This book doesn’t cover any other pathways. As if you cannot possibly be allergic to something without IgE.

That’s the problem, of course. This is what most healthcare providers or science majors learn in school. They learn about allergy and anaphylaxis, but they learn about the textbook description which invariably refers to IgE mediated food anaphylaxis. They learn about peanut allergy.

I don’t have a peanut allergy. I literally don’t have a single food allergy that displays the hallmark swelling/closing airway that people expect. But I have major food allergies, some bad enough to require epinephrine, IV Benadryl, Pepcid, Solu Medrol, Zofran and IV fluids.

The problem is not just that I’m allergic to some foods. It’s that I’m not always allergic to the same foods as I was the day before. Or the same medications. Or the same environmental exposures. My reactions on a given day are the cumulative product of the amount of irritation my mast cells have experienced in the previous day or two. There is always a running tally in my mind.

There are a lot of analogies and models used to describe mast cell attacks both to patients and to people who don’t have them. I have always thought of it as a bank. You make deposits and you make withdrawals. Like this:

For the sake of simplicity, let’s assume you have $100 in a bank account. Any activity that can cause mast cell activation has to be paid for. The cost is proportionate to the amount of activation. Getting a splinter: $2. Being hot: $10. Being in direct sunlight: $10. Standing up for 20 minutes while being hot in direct sunlight: $35. Cardiovascular exercise: $40. Arguing with your spouse: $60. Moderate pain experienced in your day to day life: $50. A painful medical procedure: $70. Mild cold: $40.

Some things are too costly to ever attempt.  Undercooked egg whites: $9000.  Massive bleach exposure: $7500.

You can make deposits into the bank with medications and physical changes. Getting enough sleep: $30. Wearing loose, comfortable clothes: $15. Doing orthostatic manuevers before standing up: $10. Taking baseline mast cell medications on your normal schedule: $50. Eating food that is warm but not hot: $15. Monitoring your exercise and stopping for breaks: $15. Wearing a cooling vest on a hot day: $20. Oral Benadryl: $25. IV Benadryl: $50. Steroids: $50.

So you have this running tally in your head all day long. When you start getting close to $100, you get stressed. You know you can’t afford to spend more than $100. Things that you could have done four hours ago safely are no longer safe. Things you could eat on a day spent relaxing at home inside with comfortable ambient temperature cannot be eaten if your apartment is too hot or if you are in a lot of pain.

You are constantly trying to avoid running out of dollars before you can get home and go to bed. Part of this is because you don’t want to trigger a physical reaction. Part of it is that this phenomenon – allergies as a function of circulating histamine/mast cell activation rather than IgE – is hard to explain briefly to people who don’t have this disease. So people will see you on a super crappy day only being able to eat one thing at a party and then four months later, when your body is much less inflamed, will see you eat three things at a party. And then it’s a thing, because these people invariably think that you are faking/being overdramatic as if somehow it is worth the effort to “pretend to have allergies.” WHO FUCKING DOES THAT?

Cost for being around someone who gives you shit for not always having the same restrictions: $75.

So everyday, you get $100. Except this is the US and our banks hate us so we have overdraft. This means that you can spend more money than you have but then they charge a steep fee and so the next day, you don’t have $100. You have maybe $30 dollars. After overspending, it can take a few days to get back to baseline.

Sometimes it’s worth it. Sometimes you can sort of game your body into getting more than $100 out of a day. This is the purpose of premedication for procedures and surgery. This is the purpose of good sleep hygiene, eating safe foods, not getting stressed, taking medications appropriately and on a schedule. You can bank a little. Not as much as you can overdraft, but you can get ahead a little bit.

Today, I went to the supermarket to grab some things for lunch at work. They didn’t have organic apples that looked in decent shape. They had non-organic apples and my safe peanut butter/honey and my safe pretzel chips. I had to run through my entire day to determine how much physical activity and stress was likely to be in the rest of my day to figure out what I could (probably) safely eat for lunch.

It’s like this all day, every day. This math wouldn’t be hard except that it’s constant and unavoidable and controls my life.

The Sex Series – Part Three: Allergic reactions of the vagina and vulva

Most of what I said about kissing applies to genitally penetrating intercourse, too.  It is not uncommon for people to develop hives as a result of the vibration, pressure, heat and friction of intercourse. Swelling after sex, called postcoital edema, is also not unusual.  Sex is also a known trigger for asthma and rhinitis.  Several aspects of sex, including the heat and emotion, can activate the autonomic nervous system and cause release of mast cell mediators.  Importantly, studies have revealed that the allergic effects of sex are not due to the physical exertion (ie. exercise anaphylaxis).

While local reactions are more common, there is precedent for sex causing multisystem allergic response or anaphylaxis.  The person receiving the vaginal penetration is more likely to have anaphylaxis following sex, especially if they are strongly sensitized to food or medications.  Seminal fluid can contain food or drug allergens.  Aspirin and penicillin derivatives have been reported to cause allergic reactions from sex, called postcoital hypersensitivity. Transfer of pollens from the clothes or skin of the partner can also cause allergic reactions.

One product we have not yet discussed that can cause contact dermatitis and anaphylaxis is condoms. 25% of reactions to latex condoms cause hives over large portions of the body, angioedema and respiratory symptoms. There are latex alternative condoms, but many patients react to those as well.

Vaginally penetrating intercourse often causes microscopic tearing, mostly due to inadequate lubrication.  As a former sex educator, if you think you are using enough lubrication, you are not.  It is my personal experience that water based lubricants are better tolerated by most allergy patients for vaginal intercourse.  Silicone lubricant is popular because it’s not absorbed by the body and is therefore slicker, whereas water based lubricant often requires reapplication.  But that’s okay.  That’s why you get a whole bottle.

Contributing to the insufficient lubrication is the fact that most people don’t engage in long enough foreplay.  Foreplay provides a number of benefits: it increases naturally secreted vaginal lubrication, increases blood flow to the vagina and tells the cervix to get out of the way. 20 minutes of foreplay is often recommended as a rule of thumb in order to get the vagina in order before penetrating intercourse.

Moisture, friction and heat can cause the vulvar skin to break down. Estrogen plays a large role in keeping this tissue strong and undamaged.  Urine on the skin can cause contact dermatitis.  Malnutrition and history of genital infections can also contribute towards the reactivity of the tissue. It is also possible to be IgE positive for Candida albicans, a yeast that lives normally in the vagina.  Inflammation can upset the balance of the normal flora, resulting not only in vaginal infections but a literal allergy to Candida.

References:

Schlosser BJ. Contact dermatitis of the vulva. Dermatol Clin 2010: 28; 697-706.

Moraes PSA, Taketomi EA. Allergic vulvovaginitis. Ann Allergy Asthma Immunol 2000; 85: 253-267.

Chen WW, Baskin M. A 33-year-old woman with burning and blistering of perivaginal tissue following sexual intercourse. Annals of Allergy, Asthma & Immunology 2004; 93: 126-130.

Harlow BL, He W, Nguyen RHN. Allergic reactions and risk of vulvodynia. Ann Epidemiol 2009; 19: 771-777.

Liccardi G, et al. Intimate behavior and allergy: a narrative review. Annals of Allergy, Asthma & Immunology 2007; 99: 394-400.

Sonnex C. Genital allergy. Sex Transm Infect 2004; 80: 4-7.

The Sex Series – Part One: Kissing and allergic reactions

The avenues by which a person can suffer symptoms as a result of sex are almost endless.  I am asked often about the mechanism by which mast cell patients can react to foreplay or intercourse. The reason it has taken so long to put this series together is not because of a dearth of information, but because there is so much.  The research on this topic is deep, if not always to the point: Why do some people react badly to having sex?

There are a number of reasons why sex can cause allergic symptoms, which explains why intimacy is often fraught with anxiety for mast cell patients.  So let’s start with the entry level: kissing.

It is widely accepted that kissing can transfer allergens via saliva, or contact between skin or oral mucosa.  Allergic reaction after kissing is not even especially unusual.  5-12% of IgE food allergic patients have had at least one reaction after kissing.  Peanuts, walnuts, and tree nuts are the most common offenders.  Rash around the mouth, hives around the mouth, flushing, angioedema of lips, mouth, tongue and throat, wheezing and hives all over the body have all been reported in this situation.  Usually symptoms present within minutes, but there are literature references to reactions developing up to three hours later.

In a group of 26 volunteers that ate peanut butter, the protein reached its highest concentration in saliva five minutes after consumption.  After an hour, the protein was undetectable.  Several methods for clearing the protein were tested.  Brushing teeth, rinsing mouth, or both, waiting an hour after consumption, and waiting an hour and then chewing gum, all reduced protein concentration by over 80%.  However, waiting one hour after eating was still the most effective way to clear the protein from the mouth.

Though much less common than transfer of food allergens, it is possible to transmit medications via saliva. In literature, all reports of this phenomenon involve ingestion of β-lactam antibiotics, including penicillin derivatives.  In these cases, the patients had symptoms of oral allergy syndrome with hives over large parts of the body.

The quality of the kissing is certainly a factor.  How deep is it?  How much hard? How much friction?  How wet?  Mast cell patients often react to physical stimuli like this.  It’s not hard to imagine a situation where the pressure and heat of kissing cause local mast cell degranulation.   I found a (non-scientific) article describing a woman with aquagenic urticaria who reacts to kissing because it’s wet.  For patients allergic to sweat, that could also cause a kissing reaction.

I feel like I should throw out there that you can react to allergens returned to the mouth by vomit.  Mostly because there isn’t really anywhere else to put it.  So it’s here.  The warning about vomit is in the kissing post.  How did this get to be my life?

BUT GUESS WHAT GUYS?!?!?!? Kissing can also be good for allergy patients.  One study reported that that kissing decreased wheal response (the formation of red swollen areas) was decreased 28-34% in patient allergic to dust mite and Japanese cedar pollen.  This patient group had allergic rhinitis and atopic dermatitis.  It didn’t decrease the response to injection of histamine, which means the benefit from kissing in this study is not directly blocking histamine.  Plasma levels of neurotrophins were decreased in these patients.  Neurotrophins have a complex relationship to mast cells, so it’s possible that neurotrophins block something that tells mast cells to release histamine.

I know everyone wants to know – how can I kiss safely? So hang in there, because it’s coming.  Along with the answers to all of the “embarrassing” sex questions I have ever been asked.

References:

Liccardi G, et al. Intimate behavior and allergy: a narrative review. Annals of Allergy, Asthma & Immunology 2007; 99: 394-400.

Maloney JM, et al. Peanut allergen exposure through saliva: assessment and interventions to reduce exposure. J Allergy Clin Immunol 2006; 118: 719-724.

Liccardi G, et al. Drug allergy transmitted by passionate kissing. Lancet 2002; 359: 1700.

Sonnex C. Genital allergy. Sex Transm Infect 2004; 80: 4-7.

 

 

 

 

 

Food allergy series: Eosinophilic colitis

Eosinophilic colitis is a controversial diagnosis. It can occur secondary to a number of conditions, including worm infestation and medical reactions, but cases without a primary cause have been reported less than 100 times in literature.

Eosinophilic colitis patients often have generic lower GI symptoms, including abdominal pain, constipation, diarrhea, and rectal bleeding. More severe cases can cause malabsorption, protein losing enteropathy, colonic wall thickening, obstructive features, eosinophilic ascites and weight loss. Unusually, these symptoms have a relapsing-remitting course, with sudden, inexplicable remission from symptoms. Eosinophilic colitis affecting infants has been segregated into its own diagnoses, which are allergic proctocolitis and FPIES. These are both due to allergic reactions from food proteins.

Eosinophilic colitis most often affects otherwise healthy infants or young adults, in whom it is more often chronic. The only defined feature is a dense eosinophilic infiltration in the colon. Infiltration can be contiguous or diffuse. Endoscopy reveals edema and patchy granularity. Crypt abscesses and lymphonodular hyperplasia may be present.

One study on typical eosinophil values in patients without history of GI issues found that there was a mean eosinophil count of 17/hpf. However, the range of cell count was wide, from 1-52. 28% of biopsies averaged more than 20 eosinophils/hpf. A mean of 35/hpf was found in the cecum, with a mean of 10/hpf in the rectum. Another study found 5-35 eosinophils/hpf in the colon, with count decreasing closer to the rectum. A diagnostic marker of greater than 60 eosinophils/ 10 hpf has been suggested for eosinophilic colitis. Others have used greater than 30/hpf.

Eosinophilic colitis patients sometimes have peripheral eosinophilia and are more likely to have an elevated total serum IgE level. Some patients with eosinophilic colitis have self reported other types of EGID, but there is not yet a biopsy proven link. Interestingly, eosinophilic colitis is not related to a history of atopy. It has been linked to scleroderma and liver transplantation in children. Two cases of eosinophilic colitis have occurred in children with autism. Eosinophilic colitis is thought to occur via a CD4+ Th2 lymphocyte mediated mechanism rather than an IgE mediated mechanism.

Due to its rarity, eosinophilic colitis has not been well researched and is not well understood. In particular, the relapsing-remitting course is baffling. It is worthwhile to note that eosinophils are seen readily using the standard H&E stain employed as a first measure in hospital labs, so they are unlikely to go unseen like mast cells. Some doctors believe it presents as a part of a larger syndrome that is sometimes missed when evaluating patients.

Treatment is much the same as other eosinophilic GI diseases. Elimination dieting is strongly recommended. Corticosteroids, such as budesonide, are often employed. Azathioprine is sometimes used. Ketotifen may be used in place of steroids.

 

References:

Alfadda, Abdulrahman A., et al. Eosinophilic colitis: epidemiology, clinical features, and current management. Ther Adv Gastroenterol (2010) 4(5): 301-309.

Gonsalves, N. Food allergies and eosinophilic gastrointestinal illness. Gastroenterol Clin North Am 36: 75-91, vi.

Food allergy series: Eosinophilic esophagitis (Part 3)

A first step in addressing EoE should be to eliminate primary GERD or PPI responsive esophageal eosinophilia. This is done by using proton pump inhibitors (PPI’s) at doses of 20-40 mg, 1-2/daily for 8-12 weeks in adults and 1 mg/kg per dose, twice daily for 8-12 weeks in children. This treatment is effective when esophageal eosinophilia is due to GERD.

There is a subset of patients with primary EoE and secondary GERD. These patients may or may not meet conventional pH criteria for diagnosing reflux. In these patients, PPI’s alone are not sufficient to treat EoE.

Dietary management is a mainstay of EoE treatment. It is extremely effective in children, with near-complete resolution of symptoms and histological abnormalities. Strict use of amino acid based formula, dietary restriction based on extensive allergy testing, and elimination of most likely allergens have all been used. Elemental therapy is the most effective. Food tolerance is unlikely to be achieved, even after long term elimination. Methods at achieving food tolerance in EoE patients have not been well studied.

Corticosteroids are effective in adults and children, but disease almost always recurs even stopped. Systemic steroids should be used in emergencies only due to the host of long term problems associated with chronic use. Topical steroids are usually effective, but steroid resistance has been reported and local fungal infections can occur. Fluticasone and oral viscous budesonide have been effective in studies. Budesonide can potentially reverse esophageal fibrosis.

Some medications used to manage mast cells, which are often elevated in EoE patients, have been trialed for EoE. Cromolyn sodium has not apparent therapeutic effect for EoE patients. Leukotriene receptor antagonists might be effective at high dosages, but this is unclear. One study on TNF-a blocker did not show benefit. Disappointingly, clinical response to anti IL-5 was variable. Anti-IL-5, anti-IL-13 and anti-eotaxin are possible future therapies.

Food impaction, in which food is retained in the esophagus, requires emergency intervention. This has been found to occur in 11-55% of EoE adults across multiple studies.

Esophageal rings are commonly found in EoE patients and inherently imply stricturing. Strictures larger than 1 cm are found in 11-31% of adults with EoE. 10% of adults have narrow caliber esophagus.

19 patients with EoE have reported perforations that were spontaneous or not due to dilation. Of 14 of these, two suffered full perforations, in which esophageal or gastric contents were found in the chest cavity. Surgical intervention was required. The remaining 12 patients had partial perforations, in which limited air or contrast media moved into the mediastinum from the esophagus. Five patients had partial perforations following endoscopy without dilation. Of the 19 total, 7 needed surgery. None were fatal.

Three instances of circumferential intramural dissection have been noted, and many cases of intramural tearing, either spontaneous or subsequent to endoscopy. Intramural tears are deep lacerations reaching the esophageal submucosa. Circumferential intramural dissection occurs where the esophageal lumen comes away from the esophageal wall in a way that affects a contiguous ring.

There is no evidence that esophageal cancer or generalized EGID results as a complication or progression of EoE. Six patients have reported concurrent Barrett esophagus. However, merely having EoE is not predictive for Barrett esophagus.

Dilation is still considered controversial in the management of EoE with high grade stricturing. This is in part because of a study done before 2008 that found that in a group of 84 adults, 5% suffered perforation and 7% hospitalized for chest pains following the procedure. These rates are much higher than in patient groups who underwent dilation for non-EoE reasons. However, three more recent retrospective studies reported lower rates of complications. Of 404 patients who underwent 839 dilations, only 3% of procedures resulted in perforations – a rate of 0.8%. Perforations were partial and did not require surgery. Chest pain occurred in 5%. One patient had major bleeding that required intervention. Dilation can induce long lasting relief from dysphagia when high grade stricturing is present. Many patients have reported a preference for periodic stricturing rather than daily medication or food elimination.

 

References:

Liacouras, Chris A., et al. Eosinophilic esophagitis : Updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011, pp. 3-20.

Furata, Glenn T., et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007; 133:1342-1363.

Food allergy series: Mast cell food reactions and the low histamine diet

When I started my posts on food allergies, I listed out the causes of food hypersensitivity. Notably absent from this list was mast cell disease. Even among detailed publications on mast cell disease, food reactions are often unmentioned (though potentially subsequent anaphylaxis is usually included.) Unfortunately, food reactions in mast cell disease are still not well understood. Even among experts, the nature and importance of food reactions in overall disease is the subject of much disagreement. Some contend that food reactions are a manifestation of general mast cell reactivity, while some think the foods specifically are sources of reactions. Following this logic, some experts believe in the validity of observing a low histamine diet while others do not.

So please keep in mind that the science behind the low histamine diet is not well accepted or even well defined. I’m going to give you my general comments on the low histamine diet, how I eat and how it has worked for me. It is my personal opinion.

A low histamine diet is one which eliminates or minimizes histamine in the food consumed. I have talked at great length about histamine so I’m not going to reiterate that here. What I will say is that exogenous histamine has been shown to induce mast cell degranulation, which means that histamine from an outside source can cause degranulation. It makes sense to me as a scientist that eating histamine rich foods will cause mast cell degranulation. It especially makes sense because the most commonly problematic food substances for mast cell patients, like alcohol, vinegar and aged cheeses, are major degranulators. I have never been able to tolerate alcohol, so it made sense to me that it was because of degranulation. Again, I prefer to lean on good studies, but in the absence of that, I will accept my own experience living in this body.

Last winter, I was in a lot of pain and generally having a sucky time of life. One of the changes I discussed with my doctors was the low histamine diet. It was in the “this can’t hurt” category. I had put off elimination dieting for a long time due to time and financial constraints, but it seemed like the appropriate time to do it had arrived.

One of the first things that became aware to me was that there is no universally agreed upon low histamine diet. There are lots of websites that discuss it and lay out diet guidelines and none of them are in complete agreement. So I just picked the one that seemed the most reasonable to me and went from there. As a mast cell patient, any diet you pick will require customization.

The diet I picked was the Histamine and Tyramine Restricted Diet by Janice Joneja. It can be found on the Mastocytosis Society Canada page.   I like this diet a lot. I do not know Dr. Joneja personally, but when I read diet/nutrition articles by her, I find them to be based in science. They meet my common sense rule. I’m going to summarize the general guidelines of the diet below along with my comments.

Key guidelines for a low histamine diet:

  • Anything fermented should be avoided. Fermentation produces histamine as a side product. Some are only sensitive to yeast fermented products while some find that fermentation from any organism is triggering.
  • No preservatives and no dyes.
  • No leftovers and nothing overly ripe. This is one of the harder parts of this diet, but I find it very important. Fresh or frozen products seem okay. I have mixed success with thawing frozen meat, but lots of people do it successfully. The key is to not cook something, put it in the fridge and eat it three days later.
  • No canned products.
  • No pickled products.

Milk and milk products: Avoid fermented products, like cheeses of all kinds, kefir, yogurt, sour cream, cottage cheese and cream cheese. A fair amount of milk products are allowed. Milk (cow, goat, coconut) is allowed, as are cheese type products that are made without fermentation (mascarpone, ricotta, panir.) Some versions of this diet allow mozzarella cheese and I find that it is safe for me. Ice cream is allowed if it doesn’t contain other disallowed ingredients. Cream products are okay, too.

Grains, breads: Yeast is the component most likely to be triggering in these products. Many people choose to restrict gluten due to their individual biologic reactions to it. Gluten is not specifically restricted on this diet, but I can tell you that it basically ends up being excluded anyway because gluten containing products usually also contain yeast. Pure, unbleached flour or grain of any kind is allowed. Products that use baking powder for leavening are allowed, like biscuits, soda bread, scones and muffins. Crackers without yeast are allowed, as are cereals if they don’t contain excluded ingredients, including artificial dyes or preservatives. I have a very difficult time finding low histamine baked products that are premade, so I generally make my own. It is surprisingly easy to make good tasting baked products with safe ingredients at home.

Vegetables: The list of vegetables that aren’t allowed feels really disjointed and counterintuitive. There is not much to do beyond committing it to memory. Not allowed: potato, avocado, green beans, eggplant, pumpkin, sauerkraut, spinach, sweet potato, tomato, any overly ripe vegetable. I personally can eat potato and sweet potato without any problem and do pretty much every day. Removing tomato was a revelation for me. It’s hard to live around because we use it for so much, but I really feel so much better. I will sometimes have a little for immediately get a stuffy nose and headache. All other vegetables are allowed. Any green that is NOT spinach is allowed. I eat a huge amount of squash, which is a really versatile ingredient. I get lots of different types from supermarkets or farmers’ markets and I make soups, purees, baked squash, squash lasagna, squash steaks, and a million other things. I can always tolerate it. This diet has also pushed me to get familiar with less common ingredients, like taro root, breadfruit and lotus root.

Fruits: Again, the list of fruits that aren’t allowed doesn’t provide any obvious unifying factor to quickly identify something as safe or not. Not allowed: citrus fruits, including lemon and lime; berries, including cranberries, blueberries, blackberries, gooseberries, loganberries, raspberries, strawberries; stone fruits, including apricots, cherries, nectarines, peaches, plums, prunes; bananas, grapes, currants, dates, papayas, pineapples, raisins. Allowed fruits: melons (keep in mind that some people may have an oral allergy syndrome reaction to melons), apple, pear, fig, kiwi, mango, passion fruit, rhubarb, starfruit (not safe for those with impaired kidney function), longans, lychees. I eat a lot of fruit, especially apples and mangoes.

Meat, fish and eggs: All shellfish are prohibited. They naturally have a huge amount of histamine. No processed meats (cold cuts.) Eggs are allowed if they are allowed. Raw egg white is a HUGE histamine liberator. Fish is allowed ONLY IF IT IS FRESHLY CAUGHT, GUTTED AND COOKED. There are differing opinions on what this means but several sources estimate it must be cooked in less than 30 minutes from catching. So unless you are or are married to a fisherman/woman, I think this is unlikely to happen. Any meat should be fresh or thawed from frozen. Leftover meat should not be consumed.

Legumes: Soy is the big culprit here because it’s in everything and is not allowed. Also not allowed: green peas, sugar or sweet peas, red beans and tofu. Everything else is allowed, including lima beans, chickpeas (I eat a ton of chickpeas), pinto beans, white beans, navy beans, black eyed peas, black beans, lentils (I also eat a ton of lentils), split peas, peanuts, and real peanut butter.

Nuts and seeds: All okay except for walnuts and pecans.

Oils: All okay except for oils that contain preservatives like BHA or BHT.

Spices: No anise, cinnamon, clove, curry, cayenne, nutmeg. Everything else is okay.

Sweeteners: No unpasteurized honey, chocolate, cocoa beans, cocoa. Most others are fine, including pasteurized honey, sugar (of really any kind), maple syrup, pure jams and jellies. This diet says plain, artificial sweeteners are okay. They are definitely not for me. One of the very first things I was told by mast cell specialist was not to use artificial sweeteners. So you can judge for yourself.

Drinks: A lot of drinks are restricted, including all teas. Most fruit juices and drinks have some type of unapproved ingredient. Milk, pure juices, water, mineral water and coffee are the allowed drinks. I also sometimes make “muddled” drinks where I crush some safe fruit with a mortar and pestle, make a simple syrup, and then put the muddled fruit in some soda water with some simple syrup.

Miscellaneous: Not allowed: Yeasts, yeast extract, all vinegars, flavored gelatin. Allowed: plain gelatin, cream of tartar, baking soda and baking powder.

The diet recommends a strict four week adherence to determine if it works. I think this is pretty accurate. I did it with no cheating for five weeks. It helped a lot. I slept better, I wasn’t swollen all the time and I was less nauseous. But there were some downsides. The first is that it is a royal pain in the ass if you work because you really have to cook every day. The restrictions on meat meant that I had meat about once every 2-3 weeks. Not everything freezes well so making a lot ahead of time isn’t always a good idea.

Finding recipes can be hard because the fact that they are labelled low histamine does not mean that they ARE low histamine. Please be very careful with that. I also find that some sources for low histamine recipes seem to assume a high level of economic freedom in food purchasing, as well as access to expensive and difficult to find ingredients. I can shop at Whole Foods, which has a knowledgeable staff and a good stock of ingredients for diets like these. There were several components I still cannot find. I also spent literally $1000 at Whole Foods for the five weeks when I initially did this diet.

One unexpected result of this diet was that it resensitized me to foods that I had become desensitized to. So foods that used to bother me a little now cause a severe reaction (sometimes anaphylactic, requiring epinephrine.) I understand that the reason for this is because these foods always caused reactions but I was effectively “used” to them so I didn’t notice. Regardless of the reason, my life is a lot more difficult foodwise than it used to be. I can “cheat” with some foods with medications but the reactions are still bad. I don’t always know how I feel about my choice to do the low histamine diet in my particular situation, but the fact is that since I did, I now am forced to observe a version of it, probably for life.

So that’s my run down on the low histamine diet.

 

 

Food allergy series: Eosinophilic esophagitis (Part 2)

Diagnosis of EoE can be difficult. Endoscopy with biopsy is the only reliable method currently available. Often in these patients, the esophagus may look unremarkable, so biopsies are recommended regardless of gross appearance. 2-4 biopsies from the proximal and distal esophagus should be collected. Biopsies of the gastric antrum and duodenum may also be taken to rule out other conditions.

Fibrosis of the lamina propria is present in most biopsies of both child and adult patients. Though less prevalent, this finding is still found sometimes in GERD cases. Basal zone hyperplasia, elongation of rete pegs and dilated intercellular spaces are EoE associated findings. Additionally, mast cells are increased in biopsies from EoE patients more so than GERD patients. IgE bearing cells are found more often in EoE than GERD.

There is some dispute over whether the peak value (the cell count in the single high powered field with the most eosinophils) is more representative than the average value (the average of cell counts in several high powered fields.) Some studies have found a correlation between eosinophil count and symptom presentation, while others have not. There are also some patients with active eosinophilic inflammation in the esophagus with few symptoms.

Other diagnostic methods should be included to rule out other conditions.   Esophageal manometry and pH testing in EoE children demonstrated that dysfunctional peristalsis correlated with difficulty swallowing. Esophageal manometry with pressure topography can reveal abnormal pressurization patterns in EoE that are not found in GERD. Endoscopic ultrasound has shown thickening of both the muscles and the mucosa in EoE. Impedance planimetry, a method that measures both pressure and volume changes, has recorded significant changes in compliance and distensibility of the esophageal wall in EoE patients. Barium contrast swallow testing was normal in 12/17 children with EoE, including four who had required endoscopy for food impaction. X-ray can detect stricturing of the proximal cervical esophagus. Some studies have linked motility issues to EoE, while others have found the opposite.

pH testing is usually undertaken to exclude GERD. In multiple studies, transnasal and wireless capsule pH measuring systems have shown variability in acid pH. When coupled with impedance testing, pH testing seems to correlate better with symptoms, but this has not been fully investigated yet. In children, both acid and non-acid reflux is comparable to controls.

40-50% of EoE patients have an increase in circulating eosinophils. When EoE is effectively treated with topical corticosteroids, peripheral eosinophilia has been shown to decrease. One study noted that in EoE patients, esophageal eosinophils display HLA DR, which means that they act as antigen presenting cells. Antigen presenting cells recruit other cells in the immune system and generate a strong inflammatory response.

Periostin, an extracellular matrix protein, is increased in the esophagus of EoE patients. Importantly, it correlates with eosinophil levels in EoE patients. Expression of eotaxin 1 and 3 is also increased in EoE. Fibroblast growth factor 9, IL-13, IL-15 and TGFB-1 can be elevated in both EoE and GERD.

A crucial finding in EoE research was the characterization of a signature transcriptome, which measures which genes the cells are using and which proteins they are making. This transcriptome is distinct from nonspecific chronic esophagitis, which has a peak eosinophil count or 6 or fewer eosinophils/hpf. Studies have demonstrated that the transcriptome can distinguish from GERD. Eotaxin 3 is hugely overexpressed in EoE patients. IL-13 is also overexpressed, with data to indicate that it may be the key regulator in EoE disease processes. In patients who have successfully achieved symptom remission, abnormal gene expression has returned to normal. However, some genes in epithelial cells continue to be expressed abnormally, which may factor into relapse.

Genetic studies have revealed that the first genome wide susceptibility locus for EoE is at 5q22. The study that found this common variable included 550,000 common genetic variants collected from various institutions. In this susceptibility locus lie genes associated with thymic stromal lymphopoietin (TSLP), a cytokine that influences behavior of Th2 cells. In a second study that looked at 53 potential genes that affected allergic or epithelial responses, or both, the TSLP gene was also identified as a susceptibility locus for EoE. This continued to be true when the data was controlled for atopic conditions. The TSLP receptor gene on the X chromosome has also been tied to EoE in male patients. These findings make a strong case for EoE as a Th2 mediated disease.

Another genetic factor found to be overrepresented in EoE patients was a common deletion variant in the filaggrin gene, 2282del4. This mutation has been associated strongly with atopic dermatitis. However, even in EoE patients who don’t have atopic dermatitis, this genetic variant is found more frequently than in the general population.

 

References:

Liacouras, Chris A., et al. Eosinophilic esophagitis : Updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011, pp. 3-20.

Furata, Glenn T., et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007; 133:1342-1363.

Food allergy series: Eosinophilic esophagitis (Part 1)

Eosinophilic esophagitis (EoE) is a well studied, well defined eosinophilic disease localized to the esophagus. With a few exceptions, it is usually diagnosed pathologically by a peak value of 15 eosinophils/hpf in esophagus biopsy samples. Currently, endoscopy with biopsy evaluation is the only diagnostic for EoE considered accurate, but patient symptoms must be considered to make a diagnosis.

EoE patients are mostly male, with three times more males than females affected. Most patients are atopic, with a history of other allergic conditions. EoE usually presents in childhood or in third or fourth decade of life, but can onset at any time.

Adult EoE patients present with more uniform symptoms. They have dysphagia (difficulty swallowing), food impaction and upper abdominal pain. About 15% of dysphagia cases are caused by EoE. Food impaction requiring endoscopic intervention occurs in 33-54% of EoE adults. Children with EoE have less specific symptoms and are more likely to have vomiting and generalized abdominal and chest pain.

As mentioned above, other atopic conditions are commonly found in EoE patients. 50-60% of EoE patients have had at least one atopic condition. 40-75% have allergic rhinitis, 14-70% have asthma and 4-60% have eczema.

15-43% of EoE patients have immediate IgE mediated food hypersensitivity reactions. Food induced anaphylaxis is more likely in EoE patients than in other populations. Furthermore, a history of IgE mediated food allergy is correlated with EoE in both adults and children.

Most EoE patients are sensitized to food allergens or aeroallergens as determined by skin prick testing or serum IgE values. Local IgE production and FceRI positive cells (cells that can be activated by IgE) are elevated in biopsies from EoE patients. Six separate articles have documented seasonality in symptom severity and presentation in EoE.

High amounts of eosinophils in the esophagus (esophageal eosinophilia) can be caused by a number of conditions in addition to EoE. This includes the broader classification of EGID, GERD, Celiac disease, Crohn’s disease, hypereosinophilic syndrome, achalasia, drug hypersensitivity, vasculitis, pemphigoid vegetans, connective tissue disease, graft versus host disease, and infection. It is necessary to effectively rule out these other conditions before diagnosing EoE, and this can be difficult. Particularly, it can hard to distinguish between EoE and GERD.

Some studies have reported that significant eosinophil driven inflammation occurs in the proximal esophagus of adults with EoE but not with GERD. Surface layering of eosinophils is more typical of EoE than GERD. Some reports indicate that extracellular eosinophilic granules, including eosinophil peroxidase, major basic protein and eosinophil derived neurotoxin, are more indicative of EoE than FERD.

The cut off of 15 eosinophils/hpf is also problematic for diagnosing EoE. Surface layering and microabscesses are only found when 15/hpf are present. Additionally, basal zone hyperplasia is 44% more likely with 15/hpf and over 100% more likely with 20/hpf. Some studies have found that a large proportion of adults meeting this threshold actually have GERD. Further confusing the issue, there is a growing subpopulation of GERD excluded patients diagnosed with EoE that demonstrate a response to PPIs. This situation is increasingly being referred to as PPI responsive esophageal eosinophilia rather than EoE.

 

References:

Liacouras, Chris A., et al. Eosinophilic esophagitis : Updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011, pp. 3-20.

Furata, Glenn T., et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007; 133:1342-1363.