Other food reactions: Pseudoallergies, biogenic amines, salicylate sensitivity,
eosinophilic gastrointestinal syndromes, alcohol reactions, multiple chemical sensitivity
Pseudoallergies
Pseudoallergic reactions cause allergy-like symptoms, but without identifiable sensitization
of the immune system. Potential causes include a wide range of agents, including
drugs and natural and synthetic food ingredients. The underlying mechanisms are
currently unclear, but a wide variety of effects on different cells and release
of chemically active transmitters have been documented. Prevalence estimates lie
between 1 and 60%, although conservative estimates are between 0.1 and 2% for individual
additives. Children mainly account for the high frequencies of some of the reactions.
The most common causes of pseudoallergies include
- Drugs: Non-steroidal anti-inflammatory drugs (NSAIDs) and painkillers, muscle relaxants,
and x-ray contrast media.
- Food additives: Food colorants (e.g tartrazine E102, sunset yellow E110, and many
others), antioxidants (e.g. BHA, BHT), sodium nitrate, sodium benzoate, potassium
disulphide, food flavorings, thickeners, acidifiers, covering agents, and artificial
sweeteners (e.g. aspartate).
- So-called natural foods can contain many additives to enhance shelf-life and appearance,
as well as taste
intensifiers, or may contain natural ingredients that can themselves elicit hypersensitivity
reactions.
Symptoms frequently associated with pseudoallergies are chronic skin itching (urticaria)
and rashes, chronic rhinitis (runny nose) and sinusitis, diarrhea, abdominal pain
and bloating. Asthma, edema, increased light sensitivity and shock (anaphylaxis)
can also develop.
The diagnosis of pseudoallergies is often difficult to substantiate, as there are
no specific skin, intestinal or laboratory tests, and offending ingredients are
cumbersome to identify. Elimination diets using low-pseudoallergen diets with symptom
diaries and subsequent specific provocation tests are the most effective diagnostic
means (See Elimination diets). The latter need to be performed under medical supervision,
due to the possibility of severe reactions. We suggest consulting an experienced
doctor or dietician for the diagnosis and management of this complicated clinical
situation.
Please note: some broader definitions of pseudoallergy also include the below entities,
as well as the sugar intolerances (See Food intolerances).
Links to literature: Medical review paper:
Reese I, Zuberbier
T, Bunselmeyer B, Erdmann S, Henzgen M, Fuchs T, Jäger L, Kleine-Tebbe J, Lepp
U, Niggemann B, Raithel M, Saloga J, Vieths S, Werfel T. Diagnostic approach for
suspected pseudoallergic
reaction to food ingredients. JDDG 2009;7: 70-77 (click to download pdf)
Biogenic amines, histamine or tyramine intolerance, scrombroid
poisoning
Biogenic amines, such as histamine and tyramine, are compounds formed during the
course of desired or undesired microbial fermentation of food or as a consequence
of food spoilage. Certain foods naturally contain high levels of histamine, tyramine
and/or other biogenic amines. These include:
- Cheeses (especially ripe), fermented meats, wine, dry sausage, sauerkraut, mushrooms,
miso and soy sauce, chocolate and yeast
Some individuals are more sensitive to histamine due to a deficiency in the enzyme,
diamine oxidase, which breaks down histamine in the small intestine. It is estimated
2-5% of adults suffer from histamine intolerance, but the condition remains contested
due to the absence of confirmatory clinical studies.
Some drugs also inhibit the action of this enzyme. These include:
- Antibiotics: (clavulanic acid/Augmentin; doxycyline, isoniazide), metoclopramide,
verapamil, promethazine, older antidepressants (monoamine oxidase inhibitors), possibly
herbal and nutritional supplements
Other drugs promote histamine release from immune cells, including some opioids,
muscle relaxants, x-ray contrast media, as well as alcohol.
Spoiled food and the associated bacterial breakdown are a common source of biogenic
amines. So-called scrombroid poisoning is a major reason for food reactions to fish.
Inadequately cooled, especially dark meat fish are implicated:
- Tuna, kahawai, mackerel, bonito, kingfish, but also Western Australian Salmon, sardines,
mahi-mahi and Blue Marlin.
The biogenic amines, once formed, are not destroyed by heating or re-cooling. Properly
cooled, fresh fish does not induce these reactions.
Symptoms can be a burning or itching sensation in the mouth, nausea, vomiting, flushing,
skin rash or hives, itching, diarrhea, headache, blood pressure changes (both high
or low possible), dizziness and fainting. The usual onset of the symptoms is within
a few minutes after ingestion of the food. The duration of symptom ranges from a
few hours to 24 h. No specific treatment is required, as symptoms subside spontaneously.
Some cases of asthma may be attributable to histamine intolerance.
Biogenic amine reactions are not allergic reactions and can be distinguished from
fish allergy by the typical previous tolerance of similar fish.
Links to literature: Medical review paper, with biogenic food content table:
MaintzL, Novak N. Histamine
and histamine intolerance. Am J Clin Nutr 2007;85:1185–1196 (click to download
pdf).
Salicylate sensitivity / intolerance
Salicylates are chemicals found naturally in many plants and are also an ingredient
of aspirin and other pain-relieving medications. They are widespread in fruit and
vegetables, as well as in health, beauty and household cleaning products. The frequency
of salicylate sensitivity is between 2 to 40% of patients attending allergy clinics
and between 2 to 7% of patients with gastrointestinal disorders, such as inflammatory
bowel disease. Salicylate sensitivity is not a classical allergy with immune system
involvement, but may be due to an overproduction of leucotrienes (inflammatory mediators)
and their metabolites. Individuals have differing sensitivity thresholds to salicylates
and the intolerance does not necessarily involve the entire spectrum of salicylate-containing
products.
Some examples of substances containing salicylate in higher concentrations include
the following. There is quite substantial overlap with the list shown for pseudoallergies,
probably because salicylate sensitivity may be classified as such. Many foods with
high salicylate content also have high amine content (See Biogenic
amines):
- Food: Fruit such as apples, apricots, avocados, dates,
kiwi, peaches, figs, grapes, plums, cherries, grapefruit, prunes, and many berries,
such as strawberries, blueberries, raspberries.
Nuts such as pine nuts, peanuts, pistachios, and almonds.
- Vegetables such as alfalfa, cauliflower, chicory,
cucumbers, mushrooms, radishes, olives, broad beans, eggplant, spinach, zucchini,
broccoli and hot pepper.
- Herbs, spices, and condiments such as dry spices and
powders (e.g. aniseed, cayenne, curry, dill, thyme, white vinegar, Worcester sauce),
tomato pastes and sauces, vinegar, soy sauce, jams and jellies, some cheeses.
- Beverages such as coffee, wine, beer, orange juice,
apple cider, regular and herbal tea, rum and sherry.
- Some sweets, such as peppermints, licorice, mint-flavored
gum, breath mints, ice cream, gelatin.
- Health and beauty products: fragrances, perfumes,
shampoos, conditioners, herbal remedies, lipsticks, lotions, skin cleansers, mouthwash,
mint-flavored toothpaste, shaving cream, sunscreens, tanning lotions, muscle pain
creams.
- Medications and oral chemical compounds: Alka Seltzer,
aspirin, acetylsalicylic / salicylic acid / salicylates, 5-ASA compounds (e.g. mesalazine),
various non-steroidal anti-inflammatory drugs NSAIDs), artificial food coloring
and flavoring, menthol and mint / peppermint / spearmint.
- Further ingredients to watch out for and avoid: Aloe
Vera, azo dyes, benzoates (preservatives), benzyl salicylate, BHA, BHT, disalcid,
eucalyptus oils, oil of wintergreen, red dye (#40), salicylaldehyde, salicylamide,
salsalate, yellow dyes (#5, #6).
The symptoms of salicylate sensitivity vary, but can be asthma-like, such as difficulty
in breathing, wheezing, and can also include headache, nasal congestion, skin rash,
hives and itching, swelling of the hands, face and feet, inflammation of the eyes,
stomach pain and nausea. In severe cases, salicylate sensitivity can lead to anaphylaxis,
a life-threatening reaction involving a severe drop in blood pressure, loss of consciousness,
and organ system failure. Avoiding products that contain salicylates is the best
prevention of a reaction.
Confirmation of salicylate sensitivity is based on extensive observation of dietary
and other substance exposure and correlation with symptoms. A food and drink diary
(See Food diaries)
may be useful for this purpose and an elimination diet (See Elimination diet) may
be necessary to ascertain the main offending food. An exclusion of all salicylate
containing products is neither feasible nor necessary, as the sensitivity often
involves specific products and smaller quantities may in many cases be tolerated.
We suggest consulting a specialist doctor or dietician for the diagnosis and management.
No specific test exists for salicylate sensitivity, but elevated levels of methylhistamine
in the urine may be a useful disease marker.
Links to literature: http://salicylatesensitivity.com
Eosinophilic gastrointestinal syndromes: eosinophilic esophagitis
/ oesophagitis
Since the 1990’s an increasing number of diseases associated with the infiltration
of eosinophilic cells, cells which are part of an allergic process, have been described
in various parts of the intestinal tract. We are including these syndromes here,
as many of the affected patients have accompanying allergies. A causal link to specific
allergies is difficult to establish, but over 50% of patients with eosinophilic
gastrointestinal disease have allergies, such as food or respiratory tract allergies,
have elevated numbers of eosinophilic cells and IgE in their blood and a relatively
high percentage respond favorably to elimination of the main foods causing allergies.
The most common of these diseases is eosinophilic esophagitis (EE), which can be
defined as esophagus-related symptoms, such as food getting stuck during swallowing
and sometimes also pain behind the breastbone, together with the presence of many
eosinophilic cells in the lining (mucosa) of the esophagus. These cells must persist
even after treatment with acid-blocking drugs. Examination of the esophagus using
endoscopy is often superficially normal, but tissue samples taken during endoscopy
reveal the dense infiltration with eosinophilic cells. This is a long-lasting disease,
which can lead to long-lasting changes and increasing malfunction of the esophagus.
Currently, 32 of 100,000 individuals have EE, of which over 70% are males. In children
EE is even more commonly associated with food allergies than in adults. Treatment
options in children are exclusion of the foods most frequently implicated in allergies
(such as cow’s milk protein, soy, wheat, egg, peanut, and seafood), or a crystalline
amino acid– based elemental diet. In case of non-response, or generally in
adults, steroids are sprayed into the throat using asthma-inhalers and swallowed
with good effects in over 70% of patients. In certain cases the esophagus must be
endoscopically widened (dilation), or other newer immmunoactive drugs may be appropriate.
Frequent endoscopy and tissue sampling is often necessary in the course of this
disease.
Eosinophilic syndromes in other parts of the digestive tract also exist, or sometimes
coexist with EE. Accompanying symptoms are often diffuse and vary widely (diarrhea,
vomiting, weight loss, intestinal bleeding, iron deficiency, bloating and intestinal
obstruction are most frequent) and diagnosis is by tissue sampling during endoscopy.
Children and adults of both genders can be affected. No standard treatment has been
defined, but various drugs have been successfully used.
Links to literature: Medical review papers:
•
Straumann A. Idiopathic eosinophilic gastrointestinal diseases in adults. Best Practice
& Research Clinical Gastroenterology 2008; 22: 481–496 (click to download
pdf).
•
Kagalwalla A, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, Mekin-Aladana
H, Li BUK. Effect of Six-Food Elimination Diet on Clinical and Histologic Outcomes
in Eosinophilic Esophagitis. Clin Gastro Hep 2006;4:1097–1102 (click to download
pdf).
Alcohol reactions
Reactions to alcohol are frequent, have several different possible mechanisms and
may involve different body organs. The most frequent cause is due to an enzyme deficiency
(aldehyde dehydrogenase), which typically causes flushing, irregular or increased
heart beat, headache, runny or stuffed nose, abdominal discomfort and blood pressure
changes. Approximately 50% of Asians may have this syndrome, but the use of specific
drugs (e.g. certain antibiotics) together with alcohol can cause or exacerbate the
same symptoms. Alcohol itself can also cause the release of histamine, resulting
in similar complaints.
Alcoholic beverages contain many different components, which can potentially result
in hypersensitivity reactions. These include barley, egg, grape, hop, seafood proteins,
sulphites, wheat and yeast, wasp and bee remains (venom) which may cause severe
reactions independent of alcohol itself. If these components are tolerated in other
food, they are not the cause of the reaction to alcohol. These ingredients differ
between and within types of alcoholic beverages.
Sulphites occur naturally in all wine, as well as in dried fruit, canned, bottled,
or frozen fruit and juices, jams and jellies, vinegar, some salads, yogurt and other
processed dairy goods, packaged pasta or rice mixes and may be used in the preparation
of crustaceans. They are also routinely added as preservatives to beer, champagne
and wine. They may precipitate asthma and wheezing in susceptible individuals, such
as a proportion of asthmatics. The concentrations of sulphite increase from red
wines to white wines to sweet wines, due to the amount of sulphites required to
prevent spoiling. Organic wines may have less sulphites or have no additional sulphites
added. Overall, sulphites are unlikely to be responsible for many of the headaches
and other symptoms besides respiratory effects seen during alcoholic beverage consumption.
Phenolic flavanoids (components in the skins of grapes related to tannins and responsible
for conferring anti-oxidant benefits), or some of the amino acids in red wine may
be the cause of many of the headaches reported. Red wine has a much higher content
of both tannins and flavanoids than white wine. Tyramine and histamine are more
plentiful in red than white wine and may cause symptoms in individuals intolerant
to these biogenic amines (See Biogenic amines).
Overindulgence in alcoholic beverages will lead to symptoms such as hang-over and
withdrawal effects, or even chronic damage body organs and should be avoided.
Multiple chemical sensitivity (MCS)
Multiple chemical sensitivity is briefly discussed here, as chronic allergy-like
gastrointestinal symptoms form part of the syndrome. An increasingly common chronic
condition, it is attributed to exposure to low concentrations of chemicals, triggering
a wide variety of irritant and toxic reactions in often many body organs. Suspected
substances include smoke, pesticides, plastics, synthetic fabrics, scented products,
petroleum products, solvents, volatile organic compounds, and often additionally
pollen, mites, and pet fur and dander. MCS is currently a controversial diagnosis,
which is not recognized as an organic illness by most medical associations or professional
medical groups due to the inability to reproduce the symptoms in double-blind testing
and the unusual distribution and often very low concentrations of offending chemicals.
However, a consensus statement by MCS researchers has defined the following syndrome
criteria:
- Symptoms are reproducible with repeated (chemical) exposures.
- The condition has persisted for a significant period of time.
- Low levels of exposure (lower than previously or commonly tolerated) result in manifestations
of the syndrome (i.e. increased sensitivity).
- The symptoms improve or resolve completely when the triggering chemicals are removed.
- Responses often occur to multiple chemically unrelated substances.
- Symptoms involve multiple-organ symptoms (runny nose, itchy eyes, headache, scratchy
throat, ear ache, scalp pain, mental confusion or sleepiness, palpitations of the
heart, upset stomach, nausea and/or diarrhea, abdominal cramping, aching joints).
The underlying mechanisms are poorly understand, but recent research has focused
amongst others on possible deficiencies in the body’s detoxification enzymes,
in neurotransmitter reactions to organic compounds, as well as abnormal conditioning
processes.
Symptoms of MCS differ from patient to patient and have a very broad spectrum. Overlap
with other syndromes, such as chronic fatigue, fibromyalgia, functional bowel syndromes,
is evident. Common symptoms include: burning, stinging eyes, wheezing, breathlessness,
nausea, abdominal pain and cramps, diarrhea, bloating, vomiting, fatigue, lethargy,
headache, dizziness, impaired poor memory and concentration, runny nose, sinus problems,
sore throat, cough, skin rashes, itching, increased sensitivity to light and noise,
sleeping problems, and muscle and joint pain.
Due to the complexity and continuous evolution of knowledge regarding MCS, referral
to an experienced treatment center is important.
Links to literature: different perspectives: