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December 2014

Food allergy series: Eosinophilic gastrointestinal disease (part 3)

The exact incidence of primary EGID is not known, but it has become an increasingly common diagnosis in the last ten years. EGID has been associated with food allergy and atopic conditions. 70% of patients have a family history of allergies. 50% of the time, EGID is seen without accompanying blood eosinophilia. EGID, like many conditions, is thought to have both an environmental and a genetic component. 10% of patients with EGID have an immediate family member with an EGID. Both inhaled and ingested allergens can be provocative for EGID patients.

Patients suffer from a variety of symptoms, including abdominal pain, GI motility issues, vomiting, diarrhea, dysphagia, microcytic anemia, hypoproteinemia and failure to thrive. Visually, the GI tract can be normal, so multiple biopsies from each segment are crucial for diagnosis. Malabsorption and protein losing enteropathy are often coincident in EGID patients.

EGID patients are particularly sensitive to foods. Eggs, milk and fish are the most common problematic foods for EGID patients. Though food specific IgE is often found in EGID patients, food anaphylaxis is rare in this population. Due to the coexistence of EGID and food specific IgE, it is considered a mixed IgE- cell mediated allergic disorder.

Elimination diets and avoidance of aeroallergens are first line treatments for these conditions. Elemental diet improves symptoms and lowers number of eosinophils in EE patients. Significant histological improvement of esophageal inflammation is documented in more than 70% of patients studied. Complete resolution of eosinophilic gastroenteritis is usually seen when the patient transmissions to an elemental amino acid based diet. Unfortunately, reintroduction of foods typically causes immediate onset of symptoms, and thus tolerance is not usually obtainable.

Steroids are often used for EGID acute management. Topic al steroids are sometimes used long term management when diet restriction has not improved symptoms. When treated with oral steroids for four weeks, decrease in eosinophilic count was seen and 65% of patients had complete resolution of symptoms. However, symptoms returned in most patients when steroids were stopped.

Montelukast blocks the D4 receptor of cysteinyl leukotrienes in eosinophils. Leukotrienes are responsible for eosinophil attraction, constriction of smooth muscle, airway swelling, and mucus hypersecretion. However, when leukotriene levels were measured in biopsies from EGID patients, only eosinophilic gastroenteritis patients showed a statistically significant increase in leukotrienes. Still, patients report symptom improvement for the duration of treatment, with relapse when it is removed.

A pilot study treated four patients with eosinophilic gastroenteritis with one dose of anti-IL-5 antibody, mepolizumab. IL-5, eotaxin, is a molecule released by T cells and mast cells that is critical in eosinophil activation. After treatment, there was a mean decrease of 70% in peripheral eosinophilia and 50-70% decrease in tissue eosinophilia (3 out of 4 patients.) Symptoms improved minimally. One patient had a 43% increase in GI eosinophil count following treatment. Approximately two months after treatment, half of the subjects had a significant increase in peripheral eosinophil counts and worsening of symptoms.

One EE patient received three doses of mepolizumab at four week intervals. This induced a ten fold decrease in mean tissue eosinophils, reduced inflammation and stricture, resulted in cessation of vomiting, and allowed the patient to successfully introduce solids. This result in encouraging, but controlled trials need to be undertaken.

Mast cells are both increased and activated in esophageal biopsies from patients with EGIDs. An association between mast cell numbers and severity of esophageal epithelial hyperplasia and eosinophil count has been recorded. Omalizumab has been observed in some studies to lower eosinophil counts in blood and lungs of asthmatics. Foroughi and colleagues ran a 16 week open label study with omalizumab of nine patients with allergic eosinophilic gastroenteritis, with confusing results. A study using anti-TNF medications did not appear promising.



Mueller, Susanna. Classification of eosinophilic gastrointestinal diseases. Best Practice & Research Clinical Gastroenterology 2008, 22 (3): 425-440.

Spergel, Jonathan, et al. Variation in prevalence, diagnostic criteria, and initial management options for eosinophilic gastrointestinal diseases in the United States. JPGN 2011, 52 (3): 300-306.

Jawairia, Mahreema, et al. Eosinophilic gastrointestinal diseases: review and update. ISRN Gastroenterology (2012).

Food allergy series: Eosinophilic gastrointestinal disease (Part 2)

The following are conditions that can cause a secondary increase in eosinophil count in the GI tract. These conditions should be ruled out before giving a diagnosis of EGID, which is inherently primary.

Allergy associated colitis affects adults, with females accounting for 2.5x more patients than males. The age of diagnosis ranges from 20s to 60s. It affects the colon and ileum, with rectum being unaffected. Eosinophils are found in the mucosal, muscular and submucosal layers. Studies have defined it as anywhere from 10-60 eosinophils/hpf, more than one eosinophil/hpf in the intraepithelial layer, or merely having clusters and evidence of degranulation. It is thought to be driven by an allergic response and has been found in association with NSAID allergy.

Hypereosinophilic syndrome (HES) can sometimes affect the colon. People with this condition produce too many circulating eosinophils, as evidenced by persistently high eosinophil count and affect to one or more of the heart, nervous system or bone marrow. Rarely, it can cause elevated eosinophils in the mucosal layer or deep bowel wall of the colon. The mechanism behind this is unclear, but thought to be due to IL-5 stimulating eosinophils inappropriately.

Crohn’s disease can affect the entirety of the GI tract and mostly presents initially in young adults. It can affect continuous or discontinuous portions of tissue. Ulceration, erosion, infiltrates of various inflammatory cells, including eosinophils, lymphoid nodules, granulomas, fibrosis, and vascular and neural lesions are often found on biopsy. It is thought to be due to cooperation of several factors.

Ulcerative colitis affects either diffuse or continuous areas of the left sided colon and rectum. Eosinophils are often found in the mucosa or superficial supermucosa. Edema, erosion, ulceration, granulocytes, and presence of plasma cells are common findings. The etiology is unclear.

Collagenous colitis is mostly found in middle aged and elderly patients, which are predominantly female. It can affect the colon and rectum and is usually discontinuous. Eosinophils are found in the mucosal layer, along with subepithelial collagen deposition, white cells in the intraepithelial layer,and various inflammatory infiltrates. It is thought to sometimes be associated with drug reactions.

Lymphocytic colitis can affect a person of any age. It affects diffuse portions of the colon and eosinophils are found in the mucosal layer. Intraepithelial lymphocytes are often found (surface epithelium >20 IELs per 100 epithelial cells). The etiology is unknown.

Autoimmune colitis occurs in conjunction with other autoimmune conditions. It can affect people of all ages, with activity in the small and large bowels. Eosinophils are found in the mucosal layer of affected tissue, with evidence of degranulation and crypt destruction. Mast cells are often found in the same tissue portions.

Graft versus host disease is a complication of bone marrow transplant and can affect anyone who has been a recipient of one. GvHD can affect the entirety of the body, and therefore can affect the whole length of the GI tract. Eosinophils are often identified in the mucosal layers, along with apoptotic crypt destruction, mixed inflammatory infiltrates and interepithelial lymphocytes.

Peripheral/intestinal T-cell lymphoma overwhelmingly affects adults over 50. It predominantly affects small bowel, but also the stomach and colon. Inflammatory infiltrates with many eosinophils and tumor cells are sometimes found. It is sometimes seen along with gluten-sensitive enteropathy.



Mueller, Susanna. Classification of eosinophilic gastrointestinal diseases. Best Practice & Research Clinical Gastroenterology 2008, 22 (3): 425-440.

Spergel, Jonathan, et al. Variation in prevalence, diagnostic criteria, and initial management options for eosinophilic gastrointestinal diseases in the United States. JPGN 2011, 52 (3): 300-306.

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

Future realities

I love data. I love scores, charts, trends. I collect information, categorize things, make lists. I love data because it’s not malleable, not mutable based upon your current reality. Data does not lie.

I keep track of my life in a little red binder. I record various data in color coded ink. When I woke up and what symptoms I had when I did. What time I took my medication. What I ate. What I thought about. How much pain medication I needed, if I had IV meds, my IV fluid volume. I draw my yoga routines in soft violet curves, map the routes I took to walk the dogs. And at the very bottom of each page, a hand drawn table, double lines under the header, my most important tool in tracking my health.

There are three columns: symptoms, score, notes. I might skimp on other details (on terrible days, I sometimes just write NOOOOOOOOOOOOOOOOO across the page), but I fill out this table every night. I have been doing it for almost three years. Every night in bed, I score my symptoms: nausea, vomiting, GI motility, flushing, hives, headache, GI pain, bone pain, other pain, energy level, sleep. I record how bad they were out of 10. Indelible. Immutable.

Last month, my doctor called me to discuss options for dealing with my ongoing GI issues. They all sounded really stupid. I told him they were sounded stupid. But I’m out of options that don’t sound stupid so I tried the one that seemed least likely to harm me while probably doing nothing. It has helped a shocking amount. I sleep at night. I’m not exhausted all day. I don’t have to brush vomit acid out of my mouth several times a day. I can do yoga regularly. I can cook. It makes my bone pain worse for some reason, but frankly, I don’t care. The global improvement in my symptom profile is that dramatic.

I started a liquid/ soft solid diet in October. I mostly eat pureed vegetables and protein drinks. I drink a lot of bone broth. It is boring and annoying and sometimes upsetting, but it is definitely working. I have been adjusting medication for months, trying to find the balance between coverage and not sleeping for 20 hours at a time. With the gut rest afforded by my easily digestible diet and the addition of this new medication, I seem to have found a working combination.

I saw my doctor on Tuesday. For once, we shared good news. My biopsies were mostly clean. My bloodwork is better. I will need surgery to have the (has no function, hurts and bleeds all the time) end of my GI tract removed, but this is not surprising. I am doing better. A lot better.

The thing about reality is that whatever one you are living right now feels like it has been your reality forever. When you have a bad month, you can’t remember the last time you felt good. When you feel hopeless, you can’t remember life without smothering darkness. Your current experience colors all your other experiences. It makes your present situation seem bigger and heavier and more permanent.

A year ago, I was living the darkest, coldest part of my life. Every day was a struggle. Every minute was a struggle. This was a year of telling myself every minute, “You can do this. You can do this.” Even when I was sure I couldn’t. Even when I felt hollow, my very life force long since sapped away.

But now I can line up the pages of my binder and flip through them. Like an old cartoon, a story appears: the numbers in my tables go down, and I get better. Data doesn’t lie.

I don’t know if this will last. I don’t know how hard it will be to recover from surgery. But it doesn’t matter. Right now I am packing to go to Colorado this week and going to Disney for New Year’s Eve and studying for exams and making big plans that I hope to share soon.

A year ago, I could never have believed that I would feel like this now. I am healing my body. I am recovering my life.

There is no limit to the things we can do. Reality is temporary. There is always a future. There is always the possibility of new realities.

Food allergy series: Eosinophilic gastrointestinal disease (Part 1)

Eosinophil gastrointestinal diseases (EGID) is an umbrella term that encompasses a plethora of primary conditions associated with inappropriate activity of eosinophils. Eosinophils are white blood cells that share a number of functions with mast cells. They are important to immune response to infections, especially parasites, as well as allergy. Eosinophils typically account for 6% or less of the total white blood cell count. They are found in a number of places in the body, but are not usually found in the lung, skin or esophagus without some underlying pathology. Like mast cells, they have granules filled with chemicals and can degranulate in response to stimulus. They release some chemicals in common with mast cells and some not.

Eosinophils are increased in a number of GI conditions, including allergy associated colitis in adults, allergic proctocolitis in infants, eosinophilic gastroenteritis and eosinophilic esophagitis. They are also elevated in inflammatory bowel disease, reflux esophagitis, celiac disease and other types of colitis. Increased eosinophils can be induced by several other conditions or disease states, including infection, use of certain medications, collagenous and lymphocytic colitis, connective tissue disease, neoplasia, graft vs host disease and autoimmune colitis. It can also be associated with allergy or idiopathic. Despite a fair amount of research, many papers use varying criteria for determination of disease and excess eosinophil count. This ambiguity has contributed to much confusion and will be discussed in detail in upcoming posts. Still, pathologically, eosinophils are rarely found in number in any tissue sample and if present indicate inflammation or disease.

A number of conditions can cause secondary increase of eosinophils in the GI tract. EGIDs are primary conditions and are listed below.

Eosinophilic gastroenteritis most often affects adults, with females being slightly more likely to develop it. Infants rarely have this condition, but some have been identified. Virtually the entire GI tract can be affected, but most often the stomach and small intestine. The eosinophils can be diffuse and localized to only one organ or portion of the organ. They can cause lesions mistaken for tumors. This condition is characterized by edema, “numerous” eosinophils in almost any layer, and ulcerations that can look like tumors. Eosinophilic gastroenteritis is idiopathic, but 50-70% are thought to be due to allergic responses, especially from medications.

Eosinophilic esophagitis usually first presents in people under 30. Males are more commonly affected. It is defined as 15 or more eosinophils/hpf (peak count) with eosinophils mostly found in the mucosa or muscular wall of the esophagus. Microabscesses and basal cell hyperplasia are sometimes found. It is subclassified as being allergic or non-allergic.

Eosinophilic colitis is a more controversial entity marked by nonspecific symptoms, unclear diagnostic criteria, and relapsing-remitting course. It is exceptionally rare. This will be discussed in detail in an upcoming post.

Eosinophilic gastroenteritis has much the same profile as eosinophic gastroenteritis, but the disease process is limited to the small intestine.

Allergic proctocolitis affects the rectum and/or colon of children under 2 years of age. Eosinophils can be found diffusely or focally in these patients. It is defined as more than 6 eosinophils/hpf in the lamina propria layer, and/or “elevated” eosinophils in the intraepithelial or muscular layers (considered 1-2 or “numerous” in various studies.) This is the result of food allergy, especially cow’s milk or soy.


Mueller, Susanna. Classification of eosinophilic gastrointestinal diseases. Best Practice & Research Clinical Gastroenterology 2008, 22 (3): 425-440.

Spergel, Jonathan, et al. Variation in prevalence, diagnostic criteria, and initial management options for eosinophilic gastrointestinal diseases in the United States. JPGN 2011, 52 (3): 300-306.

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

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.



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.


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: Risk factors for developing food allergies

There are a number of factors that seem to contribute to developing food allergies. Genetics seems to play an important role. One study found that that 64% of monozygotic twins had a concordance of peanut allergy, while only 7% dizygotic twins concorded. This means that in 64% of identical twin sets, either both had peanut allergies or neither did, while that was the case in only 7% of fraternal twins. Because monozygotic twins have identical genetic sequences, this finding implies a strong genetic component. HLA haplotyping has been studied, with conflicting reports on links between HLA type and allergies.

One of the most important genetic findings regards filaggrin, a skin barrier protein. Patients with a specific filaggrin mutation are more likely to develop peanut sensitization. This indicates that a damaged skin barrier could cause food sensitization and allergy, and further supports the idea that non-oral exposures can be sensitizing. Additionally, filaggrin mutation causes increased inflammatory mediators in the skin.

Generally, children with peanut or tree nut allergies react the first time the food is ingested. It is thought that they previously encountered these allergens in their environment. Household exposure to peanut was a significant risk factor for peanut allergy in infants. Peanut responsive T cells are found in the skin homing T cells in peanut allergic patients, implying that patients may first be exposed through the skin. There is not yet enough data on maternal ingestion of allergens to know if this is a risk factor. There are conflicting data sets on whether breastfeeding is protective against food allergies, and in any case, outcome appears to be dependent on the mother’s own sensitivity profile. Now seen in multiple recent studies, it seems that early oral exposure to food allergens may actually be protective against food allergy, a change from data produced over a decade ago.

Immune dysregulation is obviously involved in food allergies. Low vitamin A and vitamin D, which modulate the immune system, have been noted as risk factors. Interestingly, food allergy frequency varies with latitude, indicating a further possible connection to sun exposure and vitamin D deficiency. High fat diet can also change the composition and behavior of the microbial content of the GI microbiome. Medium chain triglycerides can increase sensitization when given along with food antigens in mice. There are mixed results with long chain fatty acids.

The changes in hygiene, cleaning products and use of antimicrobial compounds by the general public in the last decades have been implicated in many of the immune changes we have seen, including increasing autoimmune diseases and food allergies. This is known as the hygiene hypothesis, and it states that reduced exposure to microbes changes immune defense, causing improper reactivity to harmless components, like food and self cells. In food allergic mice, the gut microbiota has a very specific composition and transferring this flora set can actually make others more likely to develop food allergies. Dysbiosis has been noted in children with food allergies and a sequencing study demonstrated that food allergic children with atopic dermatitis have reduced microbial diversity in the gut.



Cecilia Berin, Hugh A. Sampson. Food allergy: an enigmatic epidemic. Trends in Immunology, Volume 34, Issue 8, August 2013, pages 390-397.

Cecilia Berin, Hugh A. Sampson. Mucosal Immunology of Food Allergy. Current Biology, Volume 23, Issue 9, May 2013, pages R389-R400.

Food allergy series: Food related allergic disorders

The term “food allergy” is generally used by medical professionals to refer to IgE mediated allergic responses. However, it is used in a broader sense by patients who have similar conditions because the term is more likely to be understood. The truth is that there are several types of allergic disorders provoked by foods. They are all listed below and will be expounded upon in the coming days.

IgE antibodies mediate the following types of reactions. All of them have immediate onset of symptoms following interaction with the antigen.

  • Oral allergy syndrome. This presentation is usually mild. It causes itching and mild swelling in the mouth, progressing into the throat about 7% of the time, with less than 2% of cases progressing to anaphylaxis. OAS occurs due to sensitization to pollens. These pollens have specific shapes that are recognized by the IgE molecules; certain raw fruits and vegetables may shapes that are close enough to be recognized by the same IgE molecules. This is known as crossreactivity. Cooking the food changes the shapes seen by the IgE molecules and is therefore cooked forms are usually safe. In birch pollen sensitive people, apples, peaches, pears and carrots can cause crossreaction; in ragweed sensitive people, melons can be problematic. This is usually diagnosed by skin testing with the raw fruits/ vegetables. OAS can persist and be problematic during the season when the offending pollens are most prevalent.
  • Asthma irritation, including rhinitis. This can be caused by inhaling the food protein. It is most common in infants and children with the exception of work exposures in adults, like Baker’s asthma. This most commonly occurs with the eight major allergens: egg, milk, wheat, soy, peanut, tree nuts, fish and shellfish. Skin testing and serum IgE measurement can be used for diagnosis.
  • Urticaria and angioedema. This occurs when an offending food is ingested or contacts the skin (contact urticaria.) Food exposures cause 20% of acute urticaria cases and 2% of chronic urticaria cases. It is much more common in children and usually occurs after exposure to the eight major allergens. Skin testing and serum IgE measurement can be used for diagnosis.
  • GI hypersensitivity.Immediate onset vomiting can occur in response to the major food allergens. Skin testing and serum IgE measurement can be used for diagnosis.
  • Food associated, exercise induced anaphylaxis. This occurs following ingestion of food after recent completion of exercise. It is thought that exercise affects the way the GI tract absorbs and digests allergens. This most commonly affects adults, with wheat, shellfish and celery being the most common foods to provoke this reaction. Skin testing, serum IgE measurement, component testing and exercise testing can be used for diagnosis.
  • Delayed food-induced anaphylaxis to meat. This occurs several hours after ingesting the meat. It occurs when the body generates antibodies to carbohydrate a-Gal, which can be induced by tick bites. Beef, pork and lamb are known to cause reactions in a-Gal sensitive people. Testing should include serum IgE to a-Gal.
  • Anaphylaxis. I have addressed this in detail before. It can occur in response to any food, but the eight major allergens are most common. It results in massive mast cell degranulation, leading to cardiovascular collapse.

Some allergic responses to food are due to both IgE mediated reactions and delayed cell-mediated reactions.

  • Atopic dermatitis. In children with AD, about 35% of moderate/severe rashes are due to food reactions. This is thought to be due to food reactive T cells locating to the skin. It is most common in infants and least common in adults. All major allergens can be causative, but egg and milk are the most common. AD is usually self limiting. Skin testing and serum IgE measurement can be used for diagnosis.
  • Eosinophilic GI disease (EGID.) Eosinophils are inflammatory cells that share a lot of functions and behaviors with mast cells. Like mast cell disease, eosinophilic disease can affect a variety of organs, most commonly the GI tract. Symptoms are widely variable and related to level of inflammation and infiltration. It often causes difficult or painful swallowing, weight loss, obstruction and edema. EGID is related to the activity of several mediators, include IL-5, eotaxin, which causes eosinophils to home to various inflamed locations. Much like mast cell disease, it can occur in response to a wide array of foods. Elimination diets are first line treatments for EGID. Endoscopy, kin testing and serum IgE measurement can be used for diagnosis, but elimination diets are often used empirically for diagnosis.

Some allergic type responses to food are not due to IgE antibodies.

  • Food protein induced enterocolitis syndrome (FPIES.) Usually found in infants, repeat exposure to certain proteins causes chronic vomiting, diarrhea, low energy and poor growth. Exposure again following a period of abstinence from offending substance can cause vomiting, diarrhea and 15% drop in blood pressure. These reactions occur about two hours after ingestion. Cow’s milk, soy, rice and oat are the most frequently reported sources, but many others have been recorded. In FPIES children, their cells are more responsive to TNF-a and less responsive to TGF-b. FPIES usually resolves with age, but can be difficult to diagnose due to skin testing and serum IgE testing usually being negative.
  • Food protein induced allergic proctocolitis. This causes mucuosy, bloody stools as a result of eosinophilic response in infants. This occurs in response to milk through breast feeding and resolves when the substance is removed from the mother’s diet.
  • Heiner syndrome. This rare condition is marked by pulmonary infiltration, upper respiratory symptoms, iron deficiency anemia and failure to thrive. It occurs in infants and is triggered specifically by milk. It is thought that there may be a milk specific IgG reaction.
  • Celiac disease. This autoimmune disease causes malabsorption and enteropathy. It is a response to gliadin, a gluten protein in wheat and other grains. It can cause bone abnormalities, IgA deficiency, dermatitis herpetiformis and a variety of other complications. It can present at any age and is lifelong. Blood testing during food challenges, GI biopsies, and testing for HLA DQ2 and DQ8.

Cell mediated reactions are not due to IgE antibodies.

  • Allergic contact dermatitis. This type of eczema occurs in response to metals in foods. This occurs mainly in adults. It is diagnosed by atopy patch testing.

Mast cell reactions to food are related to inappropriate degranulation which has not been fully characterized. Mast cell food reactions will be discussed more completely in an upcoming post.



Sicherer, Scott, Sampson, Hugh. Food allergy: Epidemiology, pathogenesis, diagnosis and treatment. J Allergy Clin Immunol 2014, 133 (2): 291-307.