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Lisa Klimas

I'm a 35 year old microbiologist and molecular biologist with systemic mastocytosis, Ehlers Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome, Adrenal Insufficiency, and an assortment of other chronic health issues. My life is pretty much a blast.

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.

References:

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.

 

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.

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.

 

References:

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.

 

Reference:

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

 

Food allergy series: Atopy, risk factors and frequency

Food allergy is used widely to describe any adverse reaction to food, but scientifically is considered to include only IgE mediated reactions. For the purposes of this series, I will use this term in the same way. However, there are several other conditions that can cause severe food reactions via different mechanisms and all will be addressed in upcoming posts.

Food allergy causes a reaction to a specific allergen following contact with the skin or mucosa, generally the mouth and GI tract. Colloquially, the terms sensitization and allergy are often used interchangeably, and while they are related, they are not the same. Sensitization is when the body makes allergen specific IgE in the blood or skin. Allergy is sensitization with accompanying symptoms.

Atopy refers to the tendency of a person to develop diseases of allergic nature, like asthma and atopic dermatitis. Having one atopic condition makes a person more likely to develop others. The term “allergic march” has been used to describe the progressive accumulation of atopic conditions from the first year of life through late childhood. Though first described in US patient groups, it has also been observed in several other countries. It typically begins with atopic dermatitis and progresses to include allergic rhinitis, asthma and food allergy. Severe eczema within the first six months of life is associated with increased risk of peanut, milk and egg allergies, for example.

Most food allergies are due to egg, cow’s milk, wheat, soy, shellfish, fish, peanuts and tree nuts. 30.4% of children with food allergy have multiple of them. Kids with multiple food allegies are more likely to have severe reactions, as are adolescents from 14-17 years of age. Peanuts, cashews, walnuts and shellfish allergies are most likely to be severe.

The largest studies on frequency of food allergy use self reported information. These types of surveys are not the gold standard. For example, it has been shown that a large number of people eliminate foods from their diets based on suspicion of allergy. These are often unnecessary. 89% of patients with atopic dermatitis were shown to have no reactions to suspect foods on oral challenge. Still, self reported studies are the largest body of data available.

Out of 38,480 households in the US, 2.4% had children with multiple food allergies and 3% had kids with history of severe allergic reaction. Across 9,667 Canadian households, there was an overall 8% rate of food allergy, in line with findings in the US. Australian studies have focused more specifically on frequency of individual allergens and have used oral food challenges in determining allergy frequency. Out of 2,848 one year old children in Melbourne, 3% were allergic to peanut and 8.9% were allergic to raw egg.

Risk factors for developing food allergies are complicated and will be addressed in greater detail in coming posts. Atopy, low vitamin D, reduced consumption of omega-3 polyunsaturated fatty acids, reduced consumption of antioxidants, increased use of antacids, obesity, increased hygiene, and delaying exposure to common allergens have all been cited as risks. Family history of food allergy as well as specific genetic alleles and HLA profiles have also been tied to food allergies.

In children, males are more likely to develop food allergies, with Black children being the most likely, and Asian children being more likely than White children. Children of immigrants living in the US are at higher risk than children born to American born parents in the US. Food allergy is associated with increased affluence, with people living in households earning more than $50,000/year being more likely to receive a diagnosis. However, it is not clear if this is due to increased access to healthcare.

Childhood food allergies are often thought to be “outgrowable.” Allergies to milk, egg, wheat and soy are more likely to resolve. Peanut, tree nut, fish and shellfish allergies are more likely to persist. Unfortunately, resolution of allergies is on a declining trend.

 

References:

Sicherer, Scott, Sampson, Hugh. Food allergy: Epidemiology, pathogenesis, diagnosis and treatment. Journal of Allergy and Clinical Immunology. 2014, 133(2): 291-307.

Sicherer, Scott, Leung, Donald. Advances in allergic skin disease, anaphylaxis and hypersensitivity reactions to food, drugs and insects in 2013. Journal of Allergy and Clinical Immunology. 2014, 133(2): 324-334.

Gupta, Ruchi, et al. Childhood food allergies: current diagnosis, treatment and management strategies. Mayo Clinic Proceedings. 2013, 88(5): 512-526.

Inconvenient: The reality of living with food allergies

Earlier this week, a video was circulating on the internet showing a school board meeting in Michigan. In it, school board members were discussing food allergies and the effect they have on foods being allowed in school.

“Well, you should just shoot them,” a school board member said. She threw her arms up and shrugged a little after she said it. She was clearly kidding. It was a joke to her. It is the sort of thing said when forced to discuss inconveniences at length. She said it because food allergies are inconvenient and she was tired of talking about inconvenient things.

Linda Grossman did not want to harm food allergic children. She was just tired of talking about food allergies.

I am also tired. I am tired of people saying things like this that are meant in jest but are insidious and disrespectful and deeply hurtful.

I am tired of people behaving like food allergies are a personality attribute, not a life threatening medical condition.

I am tired of people feeling like they have more of a right to convenience than food allergic people have to be alive.

As of 2010, an estimated 8.96% of adults and 6.53% of children in the US are food allergic. Averaged, this means that about 1/13 people in the US have food allergies. 1/13 means that on average, each classroom in the US can be expected to have 1-2 food allergic students. Among asthmatic children, the frequency of food allergy skyrockets to a whopping 24%. Childhood food allergies cost approximately 25 billion dollars a year in the US.

Frequency of food allergy rose 50% between 1997 and 2011, with peanut allergy alone tripling in that time. As many as 40% of food allergic children have previously had severe anaphylactic reactions that could have resulted in death. Severe reactions requiring hospitalization have increased sevenfold in the last ten years in Europe.

Food allergy is the most common cause of anaphylaxis outside of a hospital setting and results in 200,000 emergency department visits yearly. This equates to one person every three minutes. It is estimated that 100-200 people die from food allergies each year in the US, with numerous conflicting reports.

I am tired of food allergic people and families having to beg for steps to help prevent DEATH.

I am tired of people feeling that making practical changes to prevent people from DYING is inconvenient.

I am tired of people making jokes about a medical issue that KILLS people.

I am tired of food allergic people being excluded from everything because their LIFE THREATENING condition is INCONVENIENT for the other people there.

I am tired of living in a world that prioritizes convenience over the health and welfare of its people.

I am tired of people who should damn well know better spouting dangerously inaccurate facts about food allergy. So I’m putting all my other posts on hold and we’re going to talk about food allergies, FPIES, eosinophilic gastrointestinal disease, celiac disease, and a-gal allergy.

This is not a joke. Anaphylaxis is not a joke. Food allergic people are not jokes. It’s time to stop pretending comments like these aren’t damaging. It’s time for us to stand up and fight.

The other side of the sky

I am the type of person who experiences memory through music. I cannot always remember the vividness of color or feeling when revisiting in my mind, but one verse immerses me in the rich details of sense memories. Three right chords and I am reliving it.

A few days ago, as I was stepping into the shower, Wagon Wheel by Old Crow Medicine Show came on. Immediately, I was in Portland, Oregon last July. I was going for a walk well past midnight, my Epipens in my dress pocket, clanging against my thigh with each step. The air was still warm, humid, but not cloying; just sort of close in the way summer sometimes is. I signed along to the song in ASL as I walked, an old habit from when I was learning.

Driving across the bridge into Portland was the culmination of surviving years of surgeries and shocks and lost pieces of myself. I felt amazing there, filled with this lightness, but also sad around the edges. This disease is so unpredictable. I loved it there so much and I don’t know if I’ll ever get there again.

Last week, I scheduled an appointment with my colorectal surgeon for January to discuss the removal of the end of my GI tract. It no longer has any function and causes me a fair amount of grief. That same day, I booked my flights to Colorado. I was not feeling great emotionally because frankly I’m tired of surgeries and procedures but physically I have been feeling much better. I am sleeping at night and not vomiting every day and don’t feel like a zombie all the time. Anything better than normal feels like such an improvement.

In the next three months, I am planning to visit Florida, Minnesota, California and potentially Hong Kong. It’s a lot of travel for anyone, let alone someone like me. That’s the thing about feeling better – it gives you this artificial bravery to do things you normally wouldn’t. It makes you feel like you can do things you know you can’t. What if I could, though? What if I could do all things I think I can?

I had one of those cries in the shower that night, when Wagon Wheel came on, the kind with wrenching, full body sobs. It had been building all week. Every morning that week I woke up feeling okay and all day I waited for it to get worse. I was afraid of how bad it would feel when this good went away. I was afraid I would remember that I can’t do all these things I want to do, and I was afraid that I would be right.

When I have a really good day, I tell people that I feel like I could fly, like I could touch the sky if I wanted to. Feeling good after not for so long does strange things to your mind. It makes it feel like you can bend the limits of your reality.

Standing in the water, I had an image in my mind of me touching the sky only to have it break apart under my hand. And on the other side of the sky, there was this other place, with no limits, and it terrified me.

When I feel good, part of me is afraid of feeling bad again. But I think there is also a part that is afraid for another reason. I think part of me has no idea how to function outside of these confines my disease has built for me. I think if I was healthy tomorrow, I wouldn’t even remember how to live anymore.

 

MTHFR, folate metabolism and methylation

MTHFR (methylenetetrahydrofolate reductase) is an enzyme involved in folate metabolism. It is rate limiting, which means that if there is not enough, your body cannot metabolize enough folate; if there is too much, it metabolizes too much. How much folate your body is able to metabolize is directly related to how much MTHFR you have in your body.   Some folate broken down by your body is used to methylate DNA. There has been much conflicting evidence, but it seems that low folate in the body is associated with less DNA methylation overall, which may be associated with cancer (Crider, 2012.)

A single nucleotide polymorphism (SNP) is a change in DNA sequence in which one nucleotide (a DNA building block) is changed. Importantly, SNPs are common. In fact, they are so common that the way your body codes its DNA allows for SNPs to not change gene expression in many cases. This is called wobble. Three DNA building blocks in a row make one amino acid, which is used to build proteins that do things in the body. However, in many cases, the third building block can be any building block and it will still make the same amino acid. Please consider this. SNPs are so common that your cells know that in many cases, 1 in every 3 DNA building blocks can be anything and it won’t change a thing.

SNPs have become the topic of increased interest, both by medical and scientific professions and by lay people. It is certainly true that some SNPs play a role in development and progression of diseases. MTHFR has been found to have up to 24 reported SNPs, with two being of particular interest. These are C677T and A1298C.

The normal (or “wildtype”) form of MTHFR has a cytosine (C) nucleotide where people with the C677T mutation have a thymine nucleotide. If you have two copies of the regular gene, you are 677CC and homozygous for the regular form of the gene (the allele.) If you are 677CT, you have one copy of the allele with the SNP. If you are 677TT, you have two copies of the allele with the SNP. About 10% of North Americans are 677TT, meaning they have two copies of the mutated allele. It is most common in Hispanics and those of Mediterranean descent, next most common in Caucasians and least common in African Americans (Schneider, 1998.)

Being homozygous for 677TT can cause a mild MTHFR deficiency because that this form of the enzyme is generally less stable, which means it breaks down faster than usual. People with this profile are also more likely to develop mild hyperhomocysteinemia, an elevation of homocysteine in the blood. Homocysteine is consumed in the metabolism of folate, and because there is less MTHFR with the 677TT mutation, the homocysteine is not all getting used. It is also elevated in cases of B6, B12 and folic acid deficiency.

Increased homocysteine has been studied for its possible relationship to health issues, including increased clotting, strokes, schizophrenia and osteoporosis. Despite multiple studies (to be honest, quite a lot of studies), the results are really non-uniform. Because it was linked earlier to cardiovascular disease, multiple studies investigated the benefits of lowering homocysteine. In diabetic nephropathy patients, treating to lower homocysteine actually doubled cardiovascular events including heart attack and stroke, some leading to death, as well as decreased renal function (House, 2010.) But another study found lowering homocysteine decreased the risk of stroke by as much as 25% (Lonn, 2006.)

The effects of the C677T SNP have been most well studied in regards to development of cancers. Folic acid is a key metabolite in the development and proliferation of cells, so deficiency can be limiting to cell division. 677TT patients who are not folate deficient are actually 50% less likely to develop colorectal cancer or colorectal adenoma (Chen, 1999.) 677TT patients who are folate deficient have at least the same risk as 677CC patients and potentially more risk (Slattery, 1999.) 677TT patients are over four times less likely to develop acute lymphocytic leukemia. They have the same risk of developing acute myeloid leukemia (Skibola, 1999.) Some studies found them to have increased risk of cervical neoplasia, breast cancer, endometrial cancer and gastric cancer, but all of these studies were done on small populations (Xia, 2014.)

The other MTHFR SNP that gets a lot of attention is A1298C. At position 1298 of the MTHFR gene, the wildtype allele has adenine. In some people, it is substituted for cytosine. Wildtype is homozygous for adenine there and they are called 1298AA. If you have one copy of the SNP, you are 1298AC. If you have two copies, you are 1298CC. The A1298C has much less effect on the stability of the MTHFR protein than the C677T mutation. It is not known to cause elevation of homocysteine levels. There has been a lot of controversy over whether this mutation can cause a deficiency of BH4, tetrahydrobiopterin. BH4 is important in formation of neurotransmitters and nitric oxide, as well as consuming ammonia. Low levels of BH4 have been tied to phenylketonuria and trials with BH4 supplementation have seen encouraging results (Michals-Matalon, 2007.)

In the last six months or so, I have read about fifty scientific papers on MTHFR or related topics. I did this because I originally planned an MTHFR post for last summer. I didn’t do a post because the data is a mess. You cannot ascertain much of use from the peer reviewed literature on the C677T and A1298C mutations – and not for lack of effort. These mutations have been very well studied.

MTHFR mutations and methylation are talked about a lot in the mast cell community. Many people believe that having an MTHFR mutation severely impacts folate metabolism, which in turn means there is not enough methylation, and this dysregulation causes overexpression of genes causing disease. I have searched thoroughly for a link. Really thoroughly. I cannot find any link that is not the idea of one person and researched by that one person, usually outside of peer reviewed settings. I cannot find any link that is not described in detail by a person who does not stand to gain financially from patients who share their beliefs. I am not saying that MTHFR is definitely not linked to mast cell disease. I’m saying I can’t find any proof that it is. I can’t even find anything that SUGGESTS that it is. Might people with these mutations feel better with appropriate folic acid supplementation? Probably. Is that the same thing as causing mast cell disease? Certainly not. It is certainly not the same thing.

I think personal stories hold a lot of power. If your personal story is that your mast cell disease is significantly better controlled by addressing your MTHFR mutation, then I think that is fantastic. I think it is entirely possible that this is the case for many. But I do not believe it causes mast cell disease. And I think everyone would feel better with appropriate levels of folate, as it is an important player in many vital reactions.

 

References:

Schneider JA, Rees DC, Liu YT, Clegg JB (May 1998). “Worldwide distribution of a common methylenetetrahydrofolate reductase mutation”. Am. J. Hum. Genet. 62 (5): 1258–60

M L Slattery, et al. Methylenetetrahydrofolate reductase, diet and risk of colon cancer. Cancer Epidemiol Biomarkers Prev., 8 (1999), PP 560S-564S.

House, AA; Eliasziw, M; Cattran, DC; Churchill, DN; Oliver, MJ; Fine, A; Dresser, GK; Spence, JD (Apr 28, 2010). “Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial.”. JAMA: the Journal of the American Medical Association 303 (16): 1603–9.

Lonn, E; Yusuf, S; Arnold, MJ; Sheridan, P; Pogue, J; Micks, M; McQueen, MJ; Probstfield, J; Fodor, G; Held, C; Genest J, Jr; Heart Outcomes Prevention Evaluation (HOPE) 2, Investigators (Apr 13, 2006). “Homocysteine lowering with folic acid and B vitamins in vascular disease.”. The New England Journal of Medicine 354 (15): 1567–77

Skibola CF, Smith MT, Kane E, Roman E, Rollinson S, Cartwright RA, Morgan G’ (October 1999). “Polymorphisms in the methylenetetrahydrofolate reductase gene are associated with susceptibility to acute leukemia in adults”. Proc. Natl. Acad. Sci. U.S.A. 96 (22): 12810–5.

Kim, Y I, et al. Methylenetetrahydrofolate reductase polymorphisms, folate and cancer risk: a paradigm of gene-nutrient interactions in carcinogenesis. Nutr Rev 58 (2000), pp 205-209.

Crider, Krista, et al. Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate’s Role. Adv Nutr January 2012 Adv Nutr vol. 3: 21-38, 2012

Xia, Lei-Zhou, et al. Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility. World J Gastroenterol. Aug 28, 2014; 20(32): 11429–11438.

J Chen, et al. MTHFR polymorphism, methyl-replete diets and the risk of colorectal carcinoma and adenoma among US men and women: an example of gene–environment interactions in colorectal tumorigenesis. J. Nutr., 129 (1999), pp. 560S–564S