The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 61

75. What other diseases and disorders are commonly associated with mast cell disease?

I often joke that it would be easier to list what conditions are not commonly associated with mast cell disease because so many conditions occur alongside it. However, there are some conditions that you see a lot in the mast cell population relative to others. In every instance, mast cell disease has the potential to irritate the other condition and vice verse.

Clonal hematologic disorders. Systemic mastocytosis is so frequently accompanied by other blood disorders that it has a diagnosis specifically for this phenomenon: systemic mastocytosis with associated hematologic disorder (SM-AHD). It is estimated that up to 40% of patients with SM eventually develop another clonal hematologic disorder. A clonal hematologic disorder is a condition in which your bone marrow makes too many blood cells. Examples include chronic myelogenous leukemia, acute myeloid leukemia, polycythemia vera, myelofibrosis, and essential thrombocythemia.

Unlike mastocytosis, MCAS can occur secondarily to lots of conditions. In some instances, it’s not clear if the MCAS is secondary to a condition or the condition is secondary to MCAS or neither.

Heritable connective tissue diseases. Ehlers Danlos Syndrome (EDS), is the most common connective tissue disease in the mast cell population. There are multiple types of EDS. While hypermobility type EDS (formerly called Type III) is the most common in MCAS patients, other forms occur also. Other connective tissue diseases seen in mast cell patients include Marfan Syndrome and Loeys-Dietz Syndrome.

Dysautonomia. Dysautonomia is a condition in which your body’s autonomic nervous system doesn’t regulate essential bodily functions correctly. POTS is the most common form of dysautonomia found in mast cell patients but other forms occur, too.

Mast cell patients commonly have MCAS, EDS and POTS together. They cooccur so commonly that some experts think that that this presentation is actually one overarching disease rather than three separate ones affecting mast cell patients.

Eosinophilic GI disease. Mast cells are closely related to eosinophils. They activate eosinophils and eosinophils activate them. Mast cell patients sometimes have eosinophil GI disease where eosinophils activate to lots of triggers and damage the GI tract.

Immunodeficiency. Conditions that specifically impair a person’s immunity, especially those that affect T or B cells, like SCID or CVID, are not unusual in mast cell patients.

Gastrointestinal disease. Mast cells normally live in the GI tract so they are very sensitive to GI inflammation. MCAS can occur secondarily to lots of GI diseases. Crohn’s, ulcerative colitis, inflammatory bowel disease, and irritable bowel syndrome are examples. GI disorders that specifically affect motility are also seen in mast cell disease, like gastroparesis and chronic intestinal pseudoobstruction.

Allergies. Some mast cell patients have true IgE allergies or other allergic disorders like atopic dermatitis.

Autoimmune disease. Autoimmune disease is more common in MCAS patients than in SM patients. The specific disorder could be virtually any autoimmune condition, including rheumatoid arthritis, lupus, Hashimoto’s thyroiditis, autoimmune urticaria, and many others.

Adrenal insufficiency. The body’s mechanisms for produce stress hormones like cortisol can become dysregulated in mast cell patients. This results in a situation in which the body does not make enough steroids of its own to take care of the body during periods of stress. Patients with adrenal insufficiency are dependent upon daily steroids to stay safe.

Chiari malformation. This condition affects the space around a person’s brainstem, causing a wide array of symptoms. Some patients have surgery for this condition.

Asthma. It is difficult to draw an exact line where mast cell disease ends and asthma begins in mast cell patients as the symptoms can be virtually identical.

This list is not exhaustive. Many other conditions sometimes occur in mast cell patients.

For additional reading, please visit the following posts:
The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 31
The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 32

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Diseases, Part 57

71. What other diseases “look like” mast cell disease?

Mast cell diseases have many symptoms that are also commonly found in other disorders. This is one of the reasons why it is difficult to diagnose correctly. The following conditions have symptoms that can look like mast cell disease.

Neuroendocrine cells are specialized cells that help to pass signals from the nervous system to nearby cells, causing those cells to release hormones. There are many types of neuroendocrine tumors. Some conditions that look like mast cell disease are caused by these tumors. Symptoms from them are caused by the response of too much hormone.

Carcinoid syndrome is the result of a rare cancerous growth called carcinoid tumor. This tumor releases too much serotonin into the body. This can cause flushing, nausea, vomiting, diarrhea, difficulty breathing, and cardiovascular abnormalities such as abnormal heart rhythm. Mast cells also release serotonin but they release much less than carcinoid tumors.

VIPoma means vasoactive intestinal peptide –oma. When a word has –oma at the end, it means that it is a tumor. A VIPoma is a tumor that starts in the pancreas. It releases a chemical called vasoactive intestinal peptide. VIPoma can cause flushing, low blood pressure, and severe diarrhea leading to dehydration. A VIPoma can also abnormalities in the composition of the blood. Many patients have low potassium, high calcium, and high blood sugar.

Pheochromocytomas start as cells in the adrenal glands. They release excessive norepinephrine and epinephrine. They can cause headaches, heart palpitations, anxiety, and blood pressure abnormalities, among other things.

Zollinger-Ellison syndrome is a condition in which tumors release too much of a hormone called gastrin into the GI tract. This causes the stomach to make too much acid, damaging the stomach and affecting absorption.

Some blood cancers can cause mast cells to become overly activated. They may also cause an increase in tryptase, an important marker in diagnosing systemic mastocytosis.

Some other cancerous tumors like medullary thyroid carcinoma can cause mast cell type symptoms including flushing, diarrhea, and itching.

Most diseases with any allergic component can look like mast cell disease.

Eosinophilic gastrointestinal disease occurs when certain white blood cells called eosinophils become too reactive, causing inflammation to many triggers. Furthermore, people are more frequently being diagnosed with both EGID and mast cell disease.

Celiac disease is an autoimmune disease in which gluten causes an inflammatory reaction inside the body. The damage to the GI tract can be significant. Malabsorption is not unusual. Children with celiac disease may grow poorly. Bloating, diarrhea, ulceration, and abdominal pain are commonly reported.

FPIES (food protein induced enterocolitis syndrome) can cause episodes of vomiting, acidosis, low blood pressure and shock as a result of ingesting a food trigger.

Traditional (IgE) allergies can also look just like mast cell disease. They are usually distinguished by the fact that mast cell patients may react to a trigger whether or not their body specifically recognizes it as an allergen (does not make an IgE molecule to the trigger). Confusingly, it is possible to have both traditional IgE allergies and mast cell disease.

Postural orthostatic tachycardia syndrome (POTS) is commonly found in patients with mast cell disease. However, POTS itself can have similar symptoms to mast cell disease. Palpitations, blood pressure abnormalities, sweating, anxiety, nausea, and headaches are some symptoms both POTS and mast cell disease have. There are also other forms of dysautonomia which mimic the presentation of mast cell disease.

Achlorhydria is a condition in which the stomach does not produce enough acid to break down food properly. This can cause a lot of GI pain, malabsorption, anemia, and weight loss.

Hereditary angioedema and acquired angioedema are conditions that cause a person to swell, often severely. Swelling may affect the airway and can be fatal if the airway is not protected. Swelling within the abdomen can cause significant pain and GI symptoms like nausea and vomiting.

Gastroparesis is paralysis of the stomach. People with GP often experience serious GI pain, vomiting, nausea, diarrhea or constipation, bloating and swelling.

Inflammatory bowel diseases and irritable bowel syndrome can all cause GI symptoms identical to what mast cell patients experience.

This list is not exhaustive. There are many other diseases that can look similar to mast cell disease. These are the ones I have come across most commonly.

For more detailed reading, please visit the following posts:

Gastroparesis: Part 1
Gastroparesis: Treatment (part 2)
Gastroparesis: Diabetes and gastroparesis (Part 3)
Gastroparesis: Post-surgical gastroparesis (Part 4)
Gastroparesis: Less common causes (Part 5)
Gastroparesis: Autonomic nervous system and vagus nerve (Part 6)
Gastroparesis: Idiopathic gastroparesis (Part 7)

Food allergy series: Food related allergic disorders
Food allergy series: FPIES (part 1)
Food allergy series: FPIES (part 2)
Food allergy series: Eosinophilic colitis
Food allergy series: Eosinophilic gastrointestinal disease (part 1)
Food allergy series: Eosinophilic gastrointestinal disease (part 2)
Food allergy series: Eosinophilic gastrointestinal disease (part 3)
Food allergy series: Eosinophilic esophagitis (Part 1)
Food allergy series: Eosinophilic esophagitis (Part 2)
Food allergy series: Eosinophilic esophagitis (Part 3)

Angioedema: Part 1
Angioedema: Part 2
Angioedema: Part 3
Angioedema: Part 4

Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 1
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 2
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 3
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 4
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 5
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 6
Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 7

The MastAttack 107: The Layperson’s Guide to Understanding Mast Cell Disease, Part 23

I answered the 107 questions I have been asked most in the last four years. No jargon. No terminology. Just answers.

  1. Is mast cell activation the same as mast cell activation syndrome?
  • No.
  • This is the single most important clarification I make as an educator. It is crucial to understand that they aren’t the same thing, especially if you research mast cell activation syndrome online.
  • Mast cell activation is a normal and healthy process. Mast cell activation mostly means that they are ready to release chemicals in response to signals from inside the mast cell or from other cells. It is one of the major ways mast cells carry out their normal functions, like fighting infections, healing the body post trauma, and regulating the menstrual cycle.
  • Many things activate mast cells to tell mast cells to act in their normal functions. Bacteria, viruses, fungi, cancer cells, diarrhea, pain, surgery, physical or emotional stress, and many other things all activate mast cells normally. It is not surprising that these things activate mast cells because they should activate them.
  • Sometimes mast cells overreact to signals to activate, like in allergies and anaphylaxis.
  • The reason mast cell activation is a problem in mast cell disease is because mast cells respond way too strongly to activation signals. They release too many chemicals too often.
  • The other reason mast cell activation is also a problem in mast cell disease is because they become too easily activated.
  • Think of mast cells like houses. Like any house, they have doors. In healthy people, you need a lot of people knocking on the doors and windows at the same time to get the mast cell to open the doors and release chemicals. In mast cell patients, one person can knock a few times and all the doors open and release chemicals at once.

For more information, please visit this post:

The Provider Primer Series: Introduction to Mast Cells

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 Five: Seminal allergy, post-orgasmic illness syndrome and burning semen syndrome

Allergy to semen has only been well documented and studied in cisgender (non-transgender) women. Some papers go so far as to state that this problem is exclusive to (cisgender) women.  Despite this, there is evidence that (cisgender) males can have allergy to semen, including their own.  Furthermore, semen allergy is not restricted to vaginal intercourse and can be seen in anal and oral sex, as well as local reactions when semen contacts skin outside of the vaginal area.

Semen contains a number of inflammatory molecules, including TGFb1, MCP-1, IL-13 and IL-17.  MCP-1 has a well described role in mast cell activation in which it draws mast cells toward an inflammatory site and directly induces histamine release.  The physical effects of orgasm use opioids made in the body.  Some patients experience a days-long reaction to orgasm.

Termed “postorgasmic illness syndrome”, allergic symptoms affecting the genitals and general flu-like symptoms present 2-8 hours after ejaculation. These symptoms can persist for up to a week, with the day after ejaculation often being the worst.  Postorgasmic illness syndrome causes excessive sweating, rhinitis, anxiety, depression and difficulty concentrating.  This condition is recognized as a rare disorder by the NIH.  It has been hypothesized that these patients are in fact suffering from opioid withdrawal caused by the rapid depletion of opioids by orgasm.

Semen allergy has been associated with serum IgE to prostate-specific antigen (PSA), a molecule involved in the kallikrein-kinin system.  Autologous semen allergy, or allergy to one’s own semen, can be confirmed by reaction to semen in skin prick allergy testing or by specific IgE in the blood. One study found that 88% of patients who experienced burning and pain after ejaculation were positive for allergy to their own semen.

The phenomenon of burning after ejaculation is called “Burning semen syndrome”. In these patients, burning, pain and swelling of the UG tract occurs following ejaculation.  This study also evaluated partners of these patients receiving vaginal sex.  In many instances, both members of the couples evaluated were positive for allergy to semen. 89% of these couples had at least one member who exhibited allergic reaction to semen.

 

References:

Van Dijk F, et al. Non-oncological and non-infectious diseases of the penis (penile lesions). EAU-EBU Update series 4 2006; 13-19.

Ghosh D, Bernstein J. Systemic and localized seminal plasma hypersensitivity patients exhibit divergent immunologic characteristics. J Allergy Clin Immunol 2014: 134 (4): 969-972.

Jiang N, et al. Postorgasmic illness syndrome (POIS) in a Chinese man: No proof for IgE-mediated allergy to semen. J Sex Med 2015; 12: 840-845.

Bernstein JA, et al. Is burning semen syndrome a variant form of seminal plasma hypersensitivity? Obstetrics & Gynecology 2003; 101 (1): 93-102.

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.

The Sex Series – Part Four: Seminal allergy

Author’s note: This series is long and covers a number of topics other than vaginally penetrating sex, including male and female orgasms, reactions of the penis, testicles and prostate, anal sex, and pelvic floor dysfunction and pelvic pain.  The first several posts are about vaginally penetrating sex because this is what I get asked the most questions about.  It is not meant to be exclusive to anyone on the basis of gender or sexual orientation.

**
It is possible to be truly allergic to semen, although this is rare.  One of the hallmarks of this condition is that it is completely preventable with condom use.

Most patients react during or after their first experience with vaginal penetration by a penis resulting in ejaculation.  Each subsequent exposure generally causes a worsening reaction. However, it is possible to develop an allergy after a number of intercourse encounters. In studies, patients with seminal allergy are allergic to semen from multiple partners, although there are anecdotes about patients reacting to semen from a single partner and not only.

This type of allergy has been linked to IgE.  The testing for this sensitivity involves skin prick tests with seminal protein that produce wheal and flare response.  Semen specific IgE is often appreciable in the blood following exposure.  Some patients have type III and type IV hypersensitivity reactions to semen and symptoms can occur days after the exposure.

Like all other forms of allergy, the range of reactions is massive.  It can range from a low level itching to anaphylaxis requiring epinephrine.  Itching, burning, redness, swelling, pain, and blistering in the vagina have all been reported. Trouble breathing, cough, wheezing, GI symptoms, generalized hives, disseminated angioedema and full anaphylaxis can occur.  Anaphylaxis has been reported in 16 cases, with one case causing loss of consciousness.

Across studies, most patients have either a personal or family history of allergic conditions.  80% of patients in one study had a family history of atopic disease.  One study found that the onset of seminal allergy often coincides with genital system conditions or procedures like hysterectomy, IUD placement or removal, pregnancy and tubal ligation.  It is hypothesized that the disruption of the normal state of immune activity in the vagina by these activities can trigger seminal allergy, but this has not been proven.

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 Two: Contact dermatitis

Symptoms affecting the genitalia as a result of vaginally penetrating intercourse are not uncommon.  Today we are going to talk about allergic and irritant reactions to products. There are other kinds of symptoms to vaginally penetrating intercourse that we will get to later on in this series.

It is not unusual for people to use specific products only in advance of having sex.  This includes things like lubrication, pleasure creams, and products for shaving and removal of hair.  Contact dermatitis can arise as a result of these products.

Contact dermatitis is inflammation of the skin following contact with a substance that irritates or generates an allergic reaction.  In case it’s not obvious, genital tissue is much more sensitive than other parts of the body.  Irritant contact dermatitis of the vulva is more common than true allergic dermatitis there.

Common irritant triggers include hygiene products like soap, shower gel, and sanitary napkins, spermicides, diaphragms, and sexual lubricants.  In some people, these triggers can also generate a true allergic dermatitis.  Additional triggers commonly associated with allergic contact dermatitis regularly include neomycin, -caine anesthetics and nickel.

Contact dermatitis of the genital (and other) areas can cause a wide range of reactions from mildly irritating to very severe.  Symptoms can include redness, swelling, itching, burning and pain, and can cause chronic thickening of the skin, fissuring of the skin, weeping of the skin and blistering.  In most patients, the substance responsible for the reaction is identified via skin patch testing.  I would not expect this to be reliable in mast cell patients given the inherently reactive nature of our skin.

Irritant contact dermatitis often shows symptoms shortly after product use. True allergic contact dermatitis is a delayed type IV hypersensitivity reaction and can take 2-3 days to appear. Many patients are able to identify the trigger by removing products and symptom resolution upon doing so. Some genital hygiene products include alcohol.  Many more include propylene glycol, a well defined trigger for vulvar dermatitis.  Products that contain sugar and/or change the pH of the internal vaginal environment disturb the natural microbial flora, causing inflammation and increased risk of infection later.

It is also possible for products used by the partner to transfer during vaginal penetration.  If the penetration is made by part of the body and not a toy, transfer can happen in either direction. For persons using toys for external or internal stimulation, it is also possible to react to the material of the product. Something to consider is that many companies sell products to clean up after sex, either to clean genitalia, toys or both.  Please look carefully at the ingredients included in those products.  Additionally, please ensure that any toys used are cleaned before and after use.

 

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: FPIES (part 2)

FPIES is usually diagnosed clinically. Endoscopy and biopsy are not necessary to diagnose, but is sometimes done to rule out other conditions.

Scopes have shown a variety of inflammatory changes in the GI tract of FPIES kids. Diffuse colitis, friable mucosa, rectal ulceration and bleeding have been observed.  Increased levels of TNFa and decreased receptors for TGF-b have been found in the GI tract. Baseline intestinal absorption is usually normal.

Biopsies have shown villous atrophy, tissue edema, crypt abscesses, increased white blood cells, including eosinophils and mast cells, and IgM and IgA containing plasma cells. Radiology showed air fluid levels (collection of both fluid and gas in the intestines), narrowing and thickening of the mucosa in the rectum and sigmoid colon and thickening of the circular folds in the small intestine. When surgery has been performed, distension of the small bowel and thickening of the jejunum has been seen.

Food specific IgE is not usually present. In one study, 21% of patients with solid food FPIES had detectable food specific IgE. 18-30% with FPIES to cow’s milk or soy have IgE for it. If IgE is found, the course of FPIES is longer. One study found a decrease in food specific IgG4 in FPIES patients along with an increase in food specific IgA.

FPIES is managed by removing the offending food. Exclusive breastfeeding can be protective. If not breastfed, use of casein hydrolysate formula is recommended. Less commonly, amino acid formula or IV fluids may be needed. Doctors recommend introducing yellow vegetables and fruits as solids rather than cereal at six months of age. Grains, legumes and poultry should be avoided for the first year of life. Once tolerance is established to one food in a high risk category, like grains, the child is more likely to tolerate other foods in the same category.

Oral food challenges (OFC) should be undertaken to determine if tolerance to the food has been achieved. A conservative approach recommends challenges every 18-24 months in patients without recent symptoms. OFCs are high risk procedures for FPIES children. The following procedure should be observed:

  • Any FPIES OFC must be physician supervised. Generally, inpatient settings are preferred, but if an outpatient setting can provide appropriate supportive care, it may be acceptable. Intravenous access should be secured prior to beginning and IV fluids and medications should be immediately available in case of reaction. ICU care is not recommended unless there is a history of near fatal reactions.
  • Blood should be drawn immediately before beginning the OFC to provide baseline complete count count and neutrophil count.
  • Over the first hour, 0.06-0.6g/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 reaction, administer 20 ml/kg boluses of normal saline.
  • In the event of severe reaction, including repetitive vomiting, profuse diarrhea, lethargy, hypotension or hypothermia, administer 1 mg/kg methylprednisolone intravenously, up to 60-80mg total. About 50% of patients who react to FPIES OFCs will need IV fluids and steroids.
  • Epinephrine must be available during FPIES OFCs for treatment of hypotension and shock. In FPIES cases, epinephrine does not resolve vomiting and lethargy.
  • In children with positive skin tests and/or food specific IgE, antihistamines should also be available during OFCs.
  • Blood should be drawn six hours after OFC to compare to baseline values. If patient has diarrhea, stool guaiac tests should be done, and stool samples should be tested for white bloods, red blood cells and eosinophils in feces.

An OFC is considered either positive or negative. Positive means there is a reaction. Negative means there is not. It is positive if the patient experiences vomiting, lethargy or diarrhea in an appropriate time frame. In the absence of symptoms, if the neutrophil count is over 3500/ul, or white blood cells, frank or occult blood, and/or eosinophils are present in feces, the challenge is still considered positive.  More than 10 leukocytes/hpf in gastric juice at the 3 hour mark has been suggested as a positive marker, but needs further investigation. In the study that noted this marker, gastric juice was obtained via orogastric feeding tubes.

One study looked at the resolution of FPIES over a ten year period. 160 subjects were included in the study. 54% were male. Median age of diagnosis was 15 months. 180 OFCs were done for 82 patients, of which 30% had obtained an FPIES diagnosis based on previous OFCs. 44% of patients reacted to cow’s milk; 41% to soy; 22.5% to rice; and 16% to oat. 65% had only one food sensitivity, 26% had two, and 9% had three or more. Most had some form of atopic disease and 39% had detectable food specific IgE. 24% had IgE specific for the food causative for their FPIES reaction. Of the patients with IgE for cow’s milk, 41% of them moved from an FPIES reaction type to an IgE allergy reaction type.

60% of FPIES cases resolve by three years of age. This finding is an average and different populations see much different results. In South Korea, 90% of patients resolve by three years of age. In the US, only 25% resolve by this age. The differences observed are thought to be due to other factors, such as the frequency of food specific IgE and atopic disease. The median age for FPIES resolution depended largely on the food: 4.7 years for rice, 4 years for oat, 6.7 years for soy, 5.1 years for milk. If milk IgE was present, the patient did not become tolerant of milk during the course of study.

FPIES overwhelmingly affects very young children. However, there are rare cases of older children and adults developing FPIES at a later age. These cases involve fish and shellfish as the offending foods.

 

References:

Leonard, Stephanie, Nowak-Wegrzyn, Anna. Food protein induced enterocolitis syndrome: an update on natural history and review of management. Ann Allergy Asthma Immunol. 2011; 107:95-101.

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

 

Food allergy series: FPIES (part 1)

Food protein induced enterocolitis syndrome (FPIES) is the most severe GI food hypersensitivity that is not IgE mediated. FPIES is thought to be caused by a delayed, cell mediated allergic pathway. This condition results in profuse, repetitive vomiting, diarrhea, acute dehydration, lethargy and weight loss. It can eventually lead to failure to thrive.

Upon challenge, an FPIES patient will typically begin with severe, repetitive vomiting 1-3 hours after ingestion; diarrhea, 2-10 hours after diarrhea; lethargy; pallor; low blood pressure; hypothermia; and abdominal distention. They will often show a spike in neutrophils, being highest around 6 hours after exposure; elevated platelets; metabolic acidosis; high methemoglobin; white blood cells in feces, including eosinophils; fecal blood, frank or occult; increased carbohydrates in stool; and elevated white blood cells in gastric juice. Vomiting is seen in 100% of episodes; lethargy in 85%; pallor in 67%; diarrhea in 24% and hypothermia in 24%.

Chronic symptoms from repeat ingestion of responsible food include intermitten, chronic vomiting; frequent, watery diarrhea, often with blood or mucus; lethargy; dehydration; abdominal distention; weight loss; and failure to thrive. Patients with chronic symptoms are often anemic; have low serum albumin; have elevated white blood cells, especially eosinophils; have metabolic acidosis, in which the body produces too much acid and the kidneys cannot remove it quickly enough; have methemoglobinemia, too much of a form of hemoglobin that binds oxygen poorly; intramural gas, gas within the wall of the bowel; and air fluid levels, a radiologic finding often associated with bowel obstruction.

About 75% of FPIES patients appear seriously ill. 15% are hypotensive enough to require hospitalization.

FPIES almost exclusively begins in infancy. Age of onset is typically between 1 and 3 months of age, but can be as late as 12 months. It is slightly more common in males, with male cases accounting for 52-60% of cases. Symptoms generally begin within 1-4 weeks of introducing cow’s milk or soy. Sometimes these substances are tolerated, but FPIES to a solid food shows, with rice being the most common offending solid. Egg is extremely rare as a cause of FPIES reactions.

FPIES has been well studied. About 30% of FPIES patients go on to develop atopic conditions, with 25-65% getting atopic dermatitis; 3-20%, asthma; and 20%, allergic rhinitis. 40-80% of patients have a family history of atopic disease and 20% have a family history of food allergies.

A history of FPIES to one grain gives a 50% chance of reaction to other grains. In cases of solid food FPIES, 80% react to more than one food. 65% were previously diagnosed with FPIES to cow’s milk or soy. 35% were breastfed.

Patients usually improve significantly within 3-10 days of beginning casein hydrolysate-based formula with or without IV fluids. In infants who have generic GI symptoms early on, switching to a hypoallergenic formula can prevent fullblown FPIES.

References:

Leonard, Stephanie, Nowak-Wegrzyn, Anna. Food protein induced enterocolitis syndrome: an update on natural history and review of management. Ann Allergy Asthma Immunol. 2011; 107:95-101.

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