What is the difference between an allergy side effect and sensitivity to a medication

Effective management of allergic diseases relies on the ability to make an precise diagnosis.[76] Allergy testing can assist confirm or law out allergies.[77][78] Correct diagnosis, counseling, and avoidance advice based on valid allergy test results reduces the incidence of symptoms and need for medications, and improves quality of life.[77] To assess the presence of allergen-specific IgE antibodies, two diverse methods can be used: a skin prick test, or an allergy blood test.

Both methods are recommended, and they own similar diagnostic value.[78][79]

Skin prick tests and blood tests are equally cost-effective, and health economic evidence shows that both tests were cost-effective compared with no test.[77] Also, early and more precise diagnoses save cost due to reduced consultations, referrals to secondary care, misdiagnosis, and emergency admissions.[80]

Allergy undergoes dynamic changes over time. Regular allergy testing of relevant allergens provides information on if and how patient management can be changed, in order to improve health and quality of life.

Annual testing is often the practice for determining whether allergy to milk, egg, soy, and wheat own been outgrown, and the testing interval is extended to 2–3 years for allergy to peanut, tree nuts, fish, and crustacean shellfish.[78] Results of follow-up testing can guide decision-making regarding whether and when it is safe to introduce or re-introduce allergenic food into the diet.[81]

Blood testing

An allergy blood test is quick and simple, and can be ordered by a licensed health care provider (e.g., an allergy specialist) or general practitioner.

Unlike skin-prick testing, a blood test can be performed irrespective of age, skin condition, medication, symptom, disease activity, and pregnancy. Adults and children of any age can get an allergy blood test. For babies and extremely young children, a single needle stick for allergy blood testing is often more tender than several skin pricks.

An allergy blood test is available through most laboratories.

A sample of the patient’s blood is sent to a laboratory for analysis, and the results are sent back a few days later. Multiple allergens can be detected with a single blood sample. Allergy blood tests are extremely safe, since the person is not exposed to any allergens during the testing procedure.

The test measures the concentration of specific IgE antibodies in the blood. Quantitative IgE test results increase the possibility of ranking how diverse substances may affect symptoms. A law of thumb is that the higher the IgE antibody worth, the greater the likelihood of symptoms.

Allergens found at low levels that today do not result in symptoms can not assist predict future symptom development. The quantitative allergy blood result can assist determine what a patient is allergic to, assist predict and follow the disease development, estimate the risk of a severe reaction, and explain cross-reactivity.[84][85]

A low entire IgE level is not adequate to law out sensitization to commonly inhaled allergens.[86]Statistical methods, such as ROC curves, predictive worth calculations, and likelihood ratios own been used to examine the relationship of various testing methods to each other.

These methods own shown that patients with a high entire IgE own a high probability of allergic sensitization, but further investigation with allergy tests for specific IgE antibodies for a carefully chosen of allergens is often warranted.

Laboratory methods to measure specific IgE antibodies for allergy testing include enzyme-linked immunosorbent assay (ELISA, or EIA),[87]radioallergosorbent test (RAST)[87] and fluorescent enzyme immunoassay (FEIA).[88]

Patch testing

Main article: Patch test

Patch testing is a method used to determine if a specific substance causes allergic inflammation of the skin. It tests for delayed reactions.

It is used to assist ascertain the cause of skin contact allergy, or contact dermatitis. Adhesive patches, generally treated with a number of common allergic chemicals or skin sensitizers, are applied to the back. The skin is then examined for possible local reactions at least twice, generally at 48 hours after application of the patch, and again two or three days later.

Other testing

Challenge testing: Challenge testing is when little amounts of a suspected allergen are introduced to the body orally, through inhalation, or via other routes. Except for testing food and medication allergies, challenges are rarely performed.

When this type of testing is chosen, it must be closely supervised by an allergist.

Elimination/challenge tests: This testing method is used most often with foods or medicines. A patient with a suspected allergen is instructed to modify his diet to totally avoid that allergen for a set time. If the patient experiences significant improvement, he may then be «challenged» by reintroducing the allergen, to see if symptoms are reproduced.

Unreliable tests: There are other types of allergy testing methods that are unreliable, including applied kinesiology (allergy testing through muscle relaxation), cytotoxicity testing, urine autoinjection, skin titration (Rinkel method), and provocative and neutralization (subcutaneous) testing or sublingual provocation.[89]

Skin prick testing

Skin testing is also known as «puncture testing» and «prick testing» due to the series of tiny punctures or pricks made into the patient’s skin.

Little amounts of suspected allergens and/or their extracts (e.g., pollen, grass, mite proteins, peanut extract) are introduced to sites on the skin marked with pen or dye (the ink/dye should be carefully selected, lest it cause an allergic response itself). A little plastic or metal device is used to puncture or prick the skin. Sometimes, the allergens are injected «intradermally» into the patient’s skin, with a needle and syringe. Common areas for testing include the inside forearm and the back.

If the patient is allergic to the substance, then a visible inflammatory reaction will generally happen within 30minutes.

This response will range from slight reddening of the skin to a full-blown hive (called «wheal and flare») in more sensitive patients similar to a mosquito bite. Interpretation of the results of the skin prick test is normally done by allergists on a scale of severity, with +/− meaning borderline reactivity, and 4+ being a large reaction. Increasingly, allergists are measuring and recording the diameter of the wheal and flare reaction. Interpretation by well-trained allergists is often guided by relevant literature.[82] Some patients may believe they own sure their own allergic sensitivity from observation, but a skin test has been shown to be much better than patient observation to detect allergy.[83]

If a serious life-threatening anaphylactic reaction has brought a patient in for evaluation, some allergists will prefer an initial blood test prior to performing the skin prick test.

Skin tests may not be an option if the patient has widespread skin disease, or has taken antihistamines in the final several days.

Differential diagnosis

Before a diagnosis of allergic disease can be confirmed, other possible causes of the presenting symptoms should be considered.[90]Vasomotor rhinitis, for example, is one of numerous illnesses that share symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis.[91] Once a diagnosis of asthma, rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy.


The allergic diseases—hay fever and asthma—have increased in the Western world over the past 2–3 decades.[] Increases in allergic asthma and other atopic disorders in industrialized nations, it is estimated, began in the s and s, with further increases occurring during the s and s,[] although some propose that a steady rise in sensitization has been occurring since the s.[] The number of new cases per year of atopy in developing countries has, in general, remained much lower.[]

Allergytype United States United Kingdom[]
Allergicrhinitis million[] (about 11% of the population[]) million (about % of the population[])
Asthma 10 million own allergic asthma (about 3% of the population).

The prevalence of asthma increased 75% from to Asthma prevalence is 39% higher in African Americans than in Europeans.[]

million (about %). In six- and seven-year-olds asthma increased from % to % over five years, during the same time the rate decreased from 31% to % in to year-olds.
Atopic eczema About 9% of the population. Between and , prevalence has increased from 3% to 10% in children.[] million (about 1% severe).

Anaphylaxis At least 40 deaths per year due to insect venom. About deaths due to penicillin anaphylaxis. About cases of anaphylaxis and 3 deaths per year are due to latex allergy.[] An estimated people die annually from anaphylaxis due to food allergy.[] Between and , 48 deaths occurred in people ranging from five months to 85 years ancient.

Insect venom Around 15% of adults own mild, localized allergic reactions. Systemic reactions happen in 3% of adults and less than 1% of children.[] Unknown
Drug allergies Anaphylactic reactions to penicillin cause deaths per year. Unknown
Food allergies About 6% of US children under age 3 and –4% of the overall US population.[citation needed] Peanut and/or tree nut (e.g. walnut

A summary diagram that explains how allergy developsDegranulation process in allergy.

Second exposure to allergen. 1 – antigen; 2 – IgE antibody; 3 – FcεRI receptor; 4 – preformed mediators (histamine, proteases, chemokines, heparin); 5 – granules; 6 – mast cell; 7 – newly formed mediators (prostaglandins, leukotrienes, thromboxanes, PAF).An allergy testing machine being operated in a diagnostic immunology labAnti-allergy immunotherapy

Food Allergy

Posted: March

Alessandro Fiocchi, MD and Vincenzo Fierro, MD
The Bambino Gesù Children’s Research Hospital
Rome, Holy See

Definition and Classification

The classification of allergic and hypersensitivity diseases was established by the European Academy of Allergy and Clinical Immunology (EAACI) and the World Allergy Organization (WAO) in (1).

The definitions and concepts of allergic and hypersensitivity conditions beyond the allergy community own often created misunderstanding (2). For an optimal clarification:

  1. the term “atopy” is used when individuals own an IgE sensitization as documented by IgE antibodies in serum or by a positive skin prick test;
  2. “hypersensitivity” is defined as “conditions clinically resembling allergy that cause objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects”, and
  3. “allergy” is defined “a hypersensitivity reaction initiated by proven or strongly suspected immunologic mechanisms”.

Based on these definitions, a correct diagnosis of allergic disease must adhere to the following conditions:

a) Compatible clinical history; and
b) Positivity to in vivo and/or in vitro tests to prove underlying mechanism and etiology.

The tests alone cannot be used because numerous people are sensitized (positive results to in vivo and/or in vitro tests), but not allergic (no reactions).

Specifically for ‘food allergy’, this term is used when a causal relationship (ideally, with a specific immunological mechanism) has been defined.

There are three wide groups of immune reactions: IgE-mediated, non-IgE-mediated and mixed. The IgE-mediated reactions are generally divided into immediate-onset reactions (arising up to 2 hours from the food ingestion) and immediate plus late-phase (in which the immediate onset symptoms are followed by prolonged or ongoing symptoms). Non-IgE-mediated reactions, which are poorly defined both clinically and scientifically, are believed to be generally T-cell-mediated.

They are typically delayed in onset, and happen 4 to 28 hours after ingestion of the offending food(s). Mixed IgE and non-IgE mediated reaction are conditions associated with food allergy involving both IgE- and non-IgE-mediated mechanisms (3).

A series of adverse reactions to foods do not involve an immune response and are not considered food allergies (4). These include metabolic disorders (for instance, lactose and alcohol intolerance), responses to pharmacologically athletic food components, as caffeine, theobromine in chocolate or tyramine in fermented cheeses, or toxic reactions.

Toxic reactions to food can happen in any patient, if a sufficient quantity of the food is ingested; they are due to toxins in the food, e.g., to histamine in scombroid fish or bacterial toxins in food.

While sometimes these, and other presumed food allergic reactions, are defined “food intolerances”, this term should not be used to define an allergic reaction (5). Host factors such as lactase deficiency, which are associated with lactose intolerance, or idiosyncratic responses may be responsible for other non-allergic reactions to foods.

Underlying Mechanisms of Food Allergy

Typical food allergies are IgE-mediated, but several reactions involve diverse immunologic mechanisms.

These food allergies are defined as non–IgE-mediated or mixed IgE- and non–IgE-mediated.

The symptoms of IgE-mediated, non-IgE–mediated, and mixed IgE- and non–IgE-mediated food allergy are presented in Table 13. IgE-mediated symptoms develop within minutes to hours of ingesting the food, non–IgE-mediated and mixed IgE- and non–IgE-mediated food allergies present with their symptoms several hours after the ingestion of the food.

All these manifestations derive from a failure to develop or a breakdown of food tolerance, resulting in excessive production of food-specific IgE antibodies or in altered cellular events, leading to allergic reactions.

Environmental influences and genetic factors of the host underlie the immunopathogenesis of food allergy and its manifestations. Some clinical studies own revised our understanding of the cause of food allergy. For example, functional genetic variants in the IL receptor b1, Toll-like receptor 9, and thymic stromal lymphopoietin genes and even IL-4 gene polymorphism own been associated with an increased risk of food sensitization (6). In the future, the elucidation of the gene-environment interactions will be crucial for understanding the food allergy pathogenesis.

Microbiome, i.e., -omic, studies are an emerging field of interest to define allergy pathogenesis and, in a not too distant future, the microbiome could offer novel therapeutic possibilities (7).


Food allergy is described as an increasing disease over time. It is generally accepted that food allergy affects approximately % of the general population, but the spread of prevalence data is wide, ranging from 1% to 10%. Precise determination of the prevalence is still one of the major problems with food allergy, considering that numerous factors influence the reported prevalence of food allergy. The varied factors include differing criteria for making food allergy diagnosis, study methodologies, geographic variation, ages, and dietary exposures to name a few.

In European birth cohorts, the incidence ranges from % (United Kingdom) to % (Greece) (8).

The most common foods, eaten separately or included as an ingredient, even in trace amounts (hidden food), that elicit hypersensitivity reactions are milk, egg, wheat, fish, and nuts.

Despite the fact that up to % of newborn during the first years of life are diagnosed as allergic to cow's milk, recent European prevalence data repair the prevalence of cow’s milk allergy (CMA) to % (9).

Within the EuroPrevall birth cohort, the mean adjusted incidence of hen’s egg allergy was % (10), while the Australian Healthnuts study reports a prevalence of 9% (11).

The prevalence of peanut allergy among children in the United Kingdom, North America, and Australia has been reported doubled in 10 years and is approximately %, %, and % respectively.

Fish allergy prevalence ranges from 0% to 7% and the prevalence of shellfish allergy from 0% to %, depending on the method used for diagnosis.

The only study using food challenges reports a prevalence of fish allergy of 0% — % and a prevalence of shellfish allergy ranging between 0% and %. Fish allergy seems more frequent in Asia (12) than in Western countries (13).

Epidemiological studies reveal that among food-allergic infants, approximately 80% will reach tolerance by the fifth birthday, but 35% of them may eventually develop hypersensitivity to other foods. Those with the highest IgE levels, with the most serious clinical manifestations (anaphylaxis and asthma), and with the wider co-sensitizations are less likely to overgrowth their food allergy.

The natural history of food allergy also depends on the specific food sensitization, with children allergic to milk and egg displaying a better prognosis than those allergic to peanuts, tree nuts and fish(14).

Cross-Reactivity and Food Allergens

Component Resolved Diagnosis (CRD) elucidated the link between a severe allergy to pollen and the increase of oral allergy syndrome (OAS), exercise induced asthma and anaphylaxis when eating certain foods. Such reactions are due to cross-reactive allergens as pathogenesis related (PR), profilins, or lipid transfer proteins (LTP). These proteins are ubiquitous in pollens, plants, fruits and food.

Individuals sensitive to home dust mites own been reported with oral allergy syndrome following ingestion of shellfish(15). Children with CMA may react to beef in up to 20% of cases, to goat’s milk in 98%, and to donkey milk in 20% of cases(16).

IgE-Mediated Food-Related Disorders

Skin Manifestations

Acute urticaria and angioedema are the most frequent manifestation of food allergy. The onset of symptoms may be rapid, within minutes, following the ingestion of the offending food. Foods most often implicated include milk, fish, vegetables and fruits.

In atopic dermatitis, also a frequent symptom of food allergy, immediate reactions can be followed by tardy cutaneous reactions.

Gastrointestinal Tract

Symptoms caused by immediate sensitivity in the gastrointestinal tract typically develop within minutes to 2 hours of ingesting the offending food. Symptoms can include lip, tongue and palatal pruritus and swelling, laryngeal oedema, nausea, abdominal cramping, vomiting and diarrhoea. Severe reactions can result in most or every symptoms associated with anaphylaxis.

Oral allergy syndrome (OAS), a form of contact urticaria confined to the lips and oropharynx, most commonly occurs in pollen-allergic patients.

Symptoms include oropharyngeal itching, with or without facial angioedema, and/or tingling of the lips, tongue, palate and throat.

Respiratory Reactions

Allergic rhinoconjunctivitis and asthma can happen following food challenge testing, but respiratory symptoms from food allergy in the absence of skin or gastrointestinal manifestations are rare. When respiratory symptoms happen following food challenge, both early- and late-phase IgE-mediated mechanisms are probably involved.

Systemic reaction: Anaphylaxis

Anaphylaxis is an explosive systemic reaction. About 50% of anaphylaxis reactions are due to food allergy. It occurs within few minutes to hours after food ingestion(17).

What is the difference between an allergy side effect and sensitivity to a medication

Ninety per cent of patients experience skin (urticaria, angioedema) plus respiratory symptoms such as asthma, rhinitis or conjunctivitis; in 30% of the cases, they also develop gastrointestinal symptoms or hypotension, and shock and cardiac arrhythmias may happen. Every of this is caused by the massive release of mediators from mast cells and basophils.

A form of anaphylaxis associated to food is the exercise-induced food-dependent anaphylaxis, occurring, generally, hours after ingestion of a food to which the individual is allergic.

Food or exercise alone will not cause this reaction.

What is the difference between an allergy side effect and sensitivity to a medication

Risk factors for food-induced anaphylaxis include asthma and previous allergic reactions to the causative food.

Table 1. Specific Food-Induced Allergic Conditions3

Non-IgE-Mediated Food Allergic Disorders


Food allergy is also linked to manifestations of delayed hypersensitivity, partially IgE-mediated and partially non-IgE-mediated. It is implicated in Eosinophilic Esophagitis, Eosinophilic gastritis and gastroenteritis, food protein-induced enterocolitis syndrome, and allergic proctocolitis.

Food protein –induced enterocolitis syndrome (FPIES)

Primarily affects infants.

In chronic forms, it presents as emesis, diarrhea, poor growth, and, in severe cases, with starvation and lethargy. In acute forms, or after re-istration of restricted foods, it may determine emesis, diarrhea, and hypotension, starting two hours following ingestion. Diarrhea may be bloody and may result in dehydration, especially in early infancy. It has been associated frequently to ingestion of cow's milk, soy, oat, wheat, and/or rice. Skin prick test to the suspected foods are generally negative, but IgE-mediated food allergy may be associated with FPIES as sometimes the two conditions co-exist or one form transforms into the another. International consensus guidelines own been developed for FPIES.(18)

Food protein-induced allergic proctocolitis (FPIAP)

FPIAP is a benign transient condition, typically starting in the first few months of life with bloody stools in well-appearing infants.

About 60% of cases happen in breast-fed babies, the remainder in infants fed cow's milk or soy protein-based formulas.

Rarely, dietary protein proctitis shows mild hypoalbuminaemia and peripheral eosinophilia. Bowel lesions are generally confined to distal large bowel; endoscopy reveals linear erosions and mucosal oedema with infiltration of eosinophils in the epithelium and lamina propria.

Food-induced pulmonary haemosiderosis (Heiner's Syndrome)

This extremely rare syndrome, affecting infants and young children, is characterized by recurrent episodes of pneumonia associated with pulmonary infiltrates, haemosiderosis, gastrointestinal blood loss, iron deficiency, anaemia, failure to thrive.

It is due to cow's milk(19); the immunologic mechanism is still unknown.

Mixed IgE and non-IgE reactions


Although it is not, strictly speaking, an allergic disease, at least one-third of infants and young children with atopic eczema own IgE-mediated food allergy. Egg allergy is the most common food hypersensitivity in children with eczema. Appropriate diagnosis of food allergy and elimination of the offending allergen leads to significant clearing or improvement of eczematous lesions in numerous young children with eczema and food allergy. Food allergens may be triggers for some acute exacerbations (20).

Allergic eosinophilic oesophagitis (EoE).

This condition may present in children with a variety of nonspecific symptoms, e.g., feeding difficulty, nausea, vomiting, heartburn, and failure to thrive.

Teenagers and adults are more likely to present with dysphagia and episodes of food impaction.

Eighty percent of patients with eosinophilic esophagitis own symptoms similar to gastroesophageal reflux, which are refractory to anti-reflux therapy. In the case of infants, the vomitus often contains stringy mucus (similar to egg albumin). Patients may also present with food refusal, dysphagia, food impaction or abdominal pain. Food induced IgE-mediated allergy has been implicated in the pathogenesis in some patients.

What is the difference between an allergy side effect and sensitivity to a medication

In eosinophilic esophagitis there may be years of unrecognized childhood subclinical disease or “silent” chronic inflammation before the diagnosis is made.(21)

Allergic eosinophilic gastritis or gastroenteritis

The exact cause of these disorders remains unknown although both IgE-mediated and T-cell-mediated reactions own been implicated. These conditions are characterized by infiltration of eosinophils in the mucosal, muscular and/or serosal layers of the stomach or little intestines. Patients present with postprandial nausea and vomiting, abdominal pain, diarrhea (occasionally steatorrhea) and weight loss in adults and failure to thrive in young infants.

Diagnosis of Food Allergy

The results of skin prick tests (SPT), IgE entire and specific antibodies, and patient histories are not predictive of true food allergy, as they are not capable to establish the causal and temporal relationship between the intake of the suspect food and the hypersensitivity reaction.

The negative predictive accuracy of a skin prick test weal of < 3mm greater than the negative control is high, generally > 95%, and is strong evidence that the food may be consumed without severe, immediate food-allergic reactions. A positive SPT, even a weal of 3 mm or more, may be clinically irrelevant, as the patient may tolerate the ingested food. SPTs may also remain positive after the development of tolerance to the specific food.

Specific IgE levels display a variable diagnostic accuracy according to the nature of the allergen, the studied population, the specific brand of the test. Using the most favorite diagnostic systems, in is conventionally accepted that kU/l is the cut-off level for a positive in-vitro test of specific IgE.

Higher levels of specific IgE for food allergens may better correlate with clinical reactivity as evidenced by challenge testing. For this reason, decision points own been proposed. While valid in the studied populations, the worth of such decision points cannot be universal (see table below).

A double blind, placebo-controlled food challenge (DBPCFC) is the preferred test to diagnose food allergy3,19. DBPCFC should be performed in specialist centers with shut supervision. Resuscitation facilities and overnight admission can be necessary in severe cases.

DBPCFC is hard to organize in numerous clinical situations, and can be replaced by open challenges in numerous situations (when there is a minimal risk of untrue interpretations due to subjective factors). When a psychological reaction is strongly suspected, a single-blinded test may also be used (22, 23).

The in vitro diagnostics can assist to identify cross-reactive allergens between pollen and foods, or foods and latex. Cross-reactive allergens include common lipid transfer proteins (LTPs), PR molecules, and profilin. Skin prick/puncture tests using commercial extracts to the implicated fruit are often negative, but a positive test may be obtained using a drop of unused juice from the incriminated fruit.

The atopy patch test (APT) is an epicutaneous skin test in which allergens commonly associated with IgE reactions can be used, although patch testing is more commonly performed for metals such as nickel, which causes a positive patch test in nickel sensitive subjects.

Although the pathogenic mechanisms of the APT own not been fully elucidated, a positive APT can predict a tardy phase reaction following oral food challenge. A positive APT may detect clinically relevant tardy phase eczematous or GI reactions in infants and children (24). This test is not useful for IgE-mediated food allergy. It is considered experimental in most parts of the world (25).

Prevention of food allergy

According to every the current guidelines, an baby with at least one first-degree relative (parent or sibling) with a history of allergic disease’ (26, 27) in specific allergic rhinitis, asthma, eczema, or food allergy (28, 29) is at greater risk for developing food allergy.

The first proposed recommendation for a large-scale prevention of food allergy has been the use of hypoallergenic (HA) formulae in case of breastfeeding failure.

This approach has reached the level of evidence to be included in the NIAID recommendations on food allergy prevention (30), but it has subsequently been questioned. (31) Earlier guidelines on allergy prevention recommended delayed exposure to solid foods, avoidance of allergenic foods, and did not include interventions aimed at promoting the infants’ immune tolerance (32). Emerging evidence, however, has led to a paradigm shift, supporting nutritional approaches such as appropriate timing of food exposure, and use of prebiotics and probiotics for allergy prevention.

The Learning Early about Peanut (LEAP) study showed that early introduction of peanuts significantly decreased the frequency of peanut allergy among children at high risk, and modulated immune responses to peanuts (33). Hence, based on these findings, the National Institutes of Health (NIH) Guidelines for the Management and Prevention of Food Allergy subsequently recommended the introduction of peanut-containing foods to “high-risk” infants early in life ( months) (34).

The World Allergy Organization (WAO)/McMaster Working Group Guidelines for Allergic Disease Prevention (GLAD-P) has also published GRADE recommendations on the use of probiotics and prebiotics for allergy prevention based on current available evidence.

The guideline panel suggested using probiotics in pregnant and breastfeeding women whose children and infants are at high risk for developing allergy29. Probiotics own been shown by numerous studies to be effective in allergy prevention, particularly in reducing allergic eczema at a rate of 9 fewer cases per pregnant women (risk ratio [RR] ), 16 fewer cases per breastfeeding women (RR ), and 5 fewer cases per infants (RR ). Ultimately, the use of probiotics should be individualized and further studies are needed to assess their effect in preventing other types of allergy and the differences among the strains of the same species of probiotic bacteria.

Concerning prebiotics, GLAD-P conditionally recommends prebiotic supplementation in non-exclusively breastfed infants, both at high and at low risk for developing allergy, but not in exclusively breastfed infants (35). These recommendations were largely based on a meta-analysis of available evidence showing that prebiotic supplementation reduces the risk of developing asthma or recurrent wheezing (RR: , 95 % CI: to ) and the risk of developing food allergy (RR: , 95 % CI: to ) (36). It has been proposed that these effects result from interactions between the gut microbiota and the gut mucosal immune system.

GLAD-P provides no recommendation at this time on prebiotic use in pregnant and breastfeeding women, owing to the lack of evidence from experimental and observational studies.

In the future, the GLAD-P guidelines may be expanded as more data from rigorously designed, adequately powered and well-executed trials become available.

Recommendations on other interventional measures, such as vitamin D supplementation, in allergy prevention are negative (37).


Food Allergen Avoidance

The foods to which an individual is allergic should be avoided, as therapeutic intervention (tertiary prevention) in patients with food allergy. It must strike a precautionary equilibrium between the demands of prohibitive measures against allergy care and quality of life. Such a dynamic endpoint is hard to assess for efficacy and safety. Avoidance measures need to be tailored to the individual’s life and disease requirements must take account o the needs of growth, the prevention of anaphylaxis and, of the benefits expected of allergen avoidance itself.

From the patient’s perspective, avoidance means meeting obstacles unshared by their non-allergic peers, thereby curtailing their quality of life.

From the physician’s outlook, education, ensuring compliance and receptiveness of both patient and caregiver are major concerns. The role of the allergist is to review in a dialectical assessment these competing factors in concert with every parties concerned. Where avoidance of the implicated food may result in nutritional deficiency, dietary supplementation is necessary3.

Processed foods may contain hidden proteins, e.g., milk, egg and soy proteins may be added to increase the protein content or enhance flavor. Peanuts and nut products are added to thicken and flavor sauces. Patients can be taught to identify hidden food components in processed foods.

Commonly used ‘hidden' proteins are casein and lactose, derived from milk, and albumin from egg. To reveal hidden food allergens, food labelling is an issue of relevance to food allergic consumers of processed or pre-packaged foods. In the European Union, 12 food items are required by law to appear on the label: cereals containing gluten, crustaceans, egg, fish, peanut, soy, milk (including lactose), tree nuts, mustard, sesame seeds, celery, and sulfites >10 mg/kg (38). Similar legislation is in effect in the US, where the Food Allergen Labeling and Consumer Protection Act provides that every food products require an ingredient statement. In these countries, the legislation has altered industry practices in some significant aspects for milk, egg, peanut, tree nuts, shellfish, fish, soy and wheat.

In other countries, hidden allergens can be exempt from specific labeling, and thus be inadvertently consumed by food allergic individuals. On both the sides of Atlantic, the regulatory problem is now the opposite concern, that is, whether too numerous foods containing trace amounts of these allergenic foods are being "overlabeled" and whether this would then potentially restrict potentially safe food choices for allergic consumers. In fact, the labeling regulations do not prescribe the indication of potential contaminants, but numerous manufacturers are now indicating, “may contain” as a warning of potential contaminations during food preparation (39).

Pharmacological therapy

Hypersensitivity reactions are often treated with medications.

. Epinephrine is the only medication that is effective for the treatment of anaphylaxis. Additional medicatioons include H1 and H2 antihistamines, corticosteroids, and prostaglandin synthetase inhibitors These drugs are only symptomatic, do not modify the natural course of the disease, and sometimes own unacceptable side effects. Anti-IgE monoclonal antibodies therapy is licensed for use in asthma and for chronic urticaria in numerous countries, and studies are under way to determine if it has a role in the management of serious food allergies.

Oral Immunotherapy

Any desensitisation protocol to both reduce the risk of major reactions and avoid nutritional restrictions in children suffering from food allergy would be highly beneficial.

The subcutaneous istration of native (40) or modified (41) peanut extracts was attempted in the past, but the shots induced systemic reactions or serious adverse effects. In the final years, the experience with oral immunotherapy has made this a common, accepted treatment in some countries. A recent systematic review concluded that oral immunotherapy is no longer experimental, but is ready for practical application (42). It should be applied to reduce the risk of inadvertent reactions, and not to modify the natural course of the disease (43). “Tolerance” in “desensitized” children disappears if the allergen is not ingested every day in therapeutic doses. However, research is ongoing and the future use of recombinant allergens (44), synthetic peptides (45),and epicutaneous therapy for desensitization in humans looks more promising (46).

Natural history

One of the most often asked parents’ questions is “How endless will my child’s food allergy last?” Given the present impossibility to modify the natural history of food allergy, the answer must take into account a series of factors.

There is a relationship between symptom severity after ingestion and the likelihood of outgrowing the problem; the more severe the reaction, the less likely that the food allergy will be outgrown. Other factors, such as sIgE antibody level and age at diagnosis, own also been associated with prognosis of food allergy, although these associations are not invariably consistent across studies (47, 48, 49). Milk allergy’s half-life is approximately two years while egg allergy’s half-life is approximately four years. Peanut allergy, once considered to be a life-long condition, can resolve in up to 30% of cases (50).

However, it is not possible to establish a half-life for a diagnosis of peanut allergy and tree nuts should still be considered as lifelong allergies.

Similarly, fish allergy is considered a long-lasting condition and reports of recovery are rare (51). However, no study has evaluated the natural history of fish allergy in infants and fish should also be regarded as causing persistent allergies.

While peanut, tree nut, fish and seafood allergy are mostly persistent conditions, little is known about the natural history of allergy to such staples as fruits, vegetables, cereals and meat.

In food allergic children, tolerance must be tested by oral challenge at regular intervals.

Often tolerance is not acquired suddenly, but there is a gradual increase of the doses tolerated at challenge. Even after years of apparent clinical tolerance, gastrointestinal symptoms of food allergy and reduced growth, . Epinephrine is the only medication that is effective for the treatment of anaphylaxis. own been reported (52).

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6. Xie J, Lotoski LC, Chooniedass R, et al. Elevated antigen-driven IL-9 responses are prominent in peanut allergic humans. PLoS One. ;7(10):e

7. Prince BT, Mandel MJ, Nadeau K, Singh AM. Gut Microbiome and the Development of Food Allergy and Allergic Disease.

What is the difference between an allergy side effect and sensitivity to a medication

Pediatric Clinics of North America. ;

8. Grimshaw KE, Bryant T, Oliver EM, et al. Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study. Clin Transl Allergy. Jan 26;

9. Schoemaker AA, Sprikkelman AB, Grimshaw KE, et al. Incidence and natural history of challenge-proven cow's milk allergy in European children — EuroPrevall birth cohort. Allergy. ;

Xepapadaki P, Fiocchi A, Grabenhenrich L et al.

Incidence and natural history of hen's egg allergy in the first 2 years of life — the EuroPrevall birth cohort study. Allergy. ;

Koplin JJ, Osborne NJ, Wake M, et every. Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol. ;

Thalayasingam M, Lee BW. Fish and shellfish allergy. Chem Immunol Allergy ;

Sicherer SH, Muñoz-Furlong A, Sampson HA. Prevalence of seafood allergy in the United States sure by a random telephone survey. J Allergy Clin Immunol ;

Kattan J. The Prevalence and Natural History of Food Allergy.

Curr Allergy Asthma Rep. ;

Matricardi PM, Kleine-Tebbe J, Hoffmann HJ. EAACI Molecular Allergology User's Guide. Pediatr Allergy Immunol May;27 Suppl

Warren CM, Jhaveri S, Warrier MR, Smith B, Gupta RS. The epidemiology of milk allergy in US children. Ann Allergy Asthma Immunol ;

Simons FE, Ebisawa M, Sanchez-Borges M, et al. update of the evidence base: World Allergy Organization anaphylaxis guidelines. World Allergy Organ J. Oct 28;

Nowak-Węgrzyn A, Chehade M, Groetch M, et al. International Consensus Guidelines for the Diagnosis and Management of Food Protein-Induced Enterocolitis Syndrome: Workgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma, and Immunology.

J Allergy Clin Immunol. Feb 3 [Epub ahead of print]

Fiocchi A, Brozek J, Schunemann HJ, Bahna SL, von Berg A, Beyer K, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. WAO Journal ;

Roerdink EM, Flokstra-de Blok BM, Blok JL, ET AL.

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Association of food allergy and atopic dermatitis exacerbations. Ann Allergy Asthma Immunol. ;

Furuta GT, Katzka DA. Eosinophilic Esophagitis. N Engl J Med ;

Komata T, Shukuya A, Imai T, Tachimoto H, Ebisawa M. Single blind food challenge using dried food powder nd Report. milk. Arerugi. ;

Komata T, Shukuya A, Imai T, Tachimoto H, Ebisawa M. Single blind food challenge using dried food powderst report. Raw whole egg and egg yolk. Arerugi. ;

Boonyaviwat O, Pacharn P, Jirapongsananuruk O, Vichyanond P, Visitsunthorn N. Role of atopy patch test for diagnosis of food allergy-related gastrointestinal symptoms in children.

Pediatr Allergy Immunol. ;

Edwards KP, Martinez BA. Atopy patch testing for foods: a review of the literature. Allergy Asthma Proc ;

Greer FR, Sicherer SH, Burks AW et al; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Allergy and Immunology. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed rics. ;

Muraro A, Halken S, Arshad SH, et al; EAACI Food Allergy and Anaphylaxis Guidelines Group.

EAACI food allergy and anaphylaxis guidelines. Primary prevention of food allergy. Allergy. ;

Boyce JA, Assa'ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. J Allergy Clin Immunol. ;(6 Suppl):S

Fiocchi A, Pawankar R, Cuello-Garcia C, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. ;

Boyce JA, Assa'ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report.

J Allergy Clin Immunol. ;(6 Suppl):S

Boyle RJ, Ierodiakonou D, Khan T, et al. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. BMJ. ;i

Fiocchi A, Assa'ad A, Bahna S; Adverse Reactions to Foods Committee; American College of Allergy, Asthma and Immunology. Food allergy and the introduction of solid foods to infants: a consensus document. Adverse Reactions to Foods Committee, American College of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. ;

Du Toit G, Roberts G, Sayre PH, et al; LEAP Study Team. Randomized trial of peanut consumption in infants at risk for peanut allergy.

N Engl J Med. ;

Togias A, Cooper SF, Acebal ML, et al. Addendum guidelines for the prevention of peanut allergy in the United States. Report of the NIAID-sponsored expert panel. Allergy Asthma Clin Immunol. ;

Cuello-Garcia CA, Fiocchi A, Pawankar R, Yepes-Nuñez JJ, Morgano GP, Zhang Y, Ahn K, Al-Hammadi S, Agarwal A, Gandhi S, Beyer K, Burks W, Canonica GW, Ebisawa M, Kamenwa R, Lee BW, Li H, Prescott S, Riva JJ, Rosenwasser L, Sampson H, Spigler M, Terracciano L, Vereda A, Waserman S, Schünemann HJ, Brożek JL. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics.

World Allergy Organ J. ;

Cuello-Garcia CA, Brożek JL, Fiocchi A, Pawankar R, Yepes-Nuñez JJ, Terracciano L, Gandhi S, Agarwal A, Zhang Y, Schünemann HJ. Probiotics for the prevention of allergy: A systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol. ;

Yepes-Nuñez JJ, Fiocchi A, Pawankar R, Cuello-Garcia CA, Zhang Y, Morgano GP, Ahn K, Al-Hammadi S, Agarwal A, Gandhi S, Beyer K, Burks W, Canonica GW, Ebisawa M, Kamenwa R, Lee BW, Li H, Prescott S, Riva JJ, Rosenwasser L, Sampson H, Spigler M, Terracciano L, Vereda A, Waserman S, Schünemann HJ, Brożek JL. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Vitamin D.

World Allergy Organ J. ;

Houben G, Burney P, Chan CH, Crevel R, Dubois A, et al. Prioritisation of allergenic foods with honor to public health relevance: Report from an ILSI Europe Food Allergy Task Force Expert Group. Food Chem Toxicol ;

Allen KJ, Turner PJ, Pawankar R, Taylor S, Sicherer S, Lack G, Rosario N, Ebisawa M, Wong G, Mills EN, Beyer K, Fiocchi A, Sampson HA. Precautionary labelling of foods for allergen content: are we ready for a global framework?

World Allergy Organ J. ;

Nelson HS, Lahr J, Law R, Bock SA, Leung DYM. Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract. J Allergy Clin Immunol; 99 –

Sampson HA. Immunological approaches to the treatment of food allergy. Pediatr Allergy Immunol;12 (suppl 14): 91 –96

Nurmatov U, Dhami S, Arasi S, et al. Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

Allergy. Jan 6. [Epub ahead of print]

Dang TD, Peters RL, Allen KJ. Debates in allergy medicine: baked egg and milk do not accelerate tolerance to egg and milk. World Allergy Organ J. ; 26;

Li XM, Srisvastava K, Grishin A, Huang C, Schofield BH, Burks AW, et al. Persistent protective effect of heat killed E. coli producing “engineered,” recombinant peanut proteins in a murine model of peanut allergy. J Allergy Clin Immunol ;

Sicherer SH, Advances in anaphylaxis and hypersensitivity reactions to foods, drugs and insect venom.

J Allergy Clin Immunol ; s

Tordesillas L, Mondoulet L, Blazquez AB, et al. Epicutaneous immunotherapy induces gastrointestinal LAP(+) regulatory T cells and prevents food-induced anaphylaxis. J Allergy Clin Immunol ;

Garcia-Ara MC, Boyano-Martinez MT, Diaz-Pena JM, Martin-Munoz MF, Martin-Esteban M. Cow's milk-specific immunoglobulin E levels as predictors of clinical reactivity in the follow-up of the cow's milk allergy infants. Clin Exp Allergy ;

Shek LP, Soderstrom L, Ahlstedt S, Beyer K, Sampson HA.

Determination of food specific IgE levels over time can predict the development of tolerance in cow's milk and hen's egg allergy. J Allergy Clin Immunol ;

Fiocchi A, Terracciano L Bouygue GR, Veglia F, Sarratud T, Martelli A, Restani P. Incremental prognostic factors associated with cow's milk allergy outcomes in baby and kid referrals: the Milan Cow's Milk Allergy Cohort study. Ann Allergy Asthma Immunol ;

Peters RL, Allen KJ, Dharmage SC,et al. Natural history of peanut allergy and predictors of resolution in the first 4 years of life: A population-based assessment.

J Allergy Clin Immunol. ;

Pite H, Prates S, Borrego LM, et al. Resolution of IgE-mediated fish allergy. Allergol Immunopathol (Madr). ;

Kokkonen J, Tikkanen S, Savilahti R: Residual intestinal disease after milk allergy in infancy. J Pediatr Gastroenterol Nutr ;

Health care providers often need to assess allergic disorders such as allergic rhinoconjunctivitis, asthma, and allergies to foods, drugs, latex, and venom, both in the hospital and in the clinic.

Unfortunately, some symptoms, such as chronic nasal symptoms, can happen in both allergic and nonallergic disorders, and this overlap can confound the diagnosis and therapy.

Studies propose that when clinicians use the history and physical examination alone in evaluating possible allergic disease, the accuracy of their diagnoses rarely exceeds 50%.1

Blood tests are now available that measure immunoglobulin E (IgE) directed against specific antigens. These in vitro tests can be significant tools in assessing a patient whose history suggests an allergic disease.2 However, neither allergy skin testing nor these blood tests are intended to be used for screening: they may be most useful as confirmatory diagnostic tests in cases in which the pretest clinical impression of allergic disease is high.

In susceptible people, IgE is produced by B cells in response to specific antigens such as foods, pollens, latex, and drugs.

This antigen-specific (or allergen-specific) IgE circulates in the serum and binds to high-affinity IgE receptors on immune effector cells such as mast cells located throughout the body.

Upon subsequent exposure to the same allergen, IgE receptors cross-link and initiate downstream signaling events that trigger mast cell degranulation and an immediate allergic response—hence the term immediate (or Gell-Coombs type I) hypersensitivity.3

Common manifestations of type I hypersensitivity reactions include signs and symptoms that can be:

  1. Cutaneous (eg, acute urticaria, angioedema)
  2. Respiratory (eg, acute bronchospasm, rhinoconjunctivitis)
  3. Cardiovascular (eg, tachycardia, hypotension)
  4. Gastrointestinal (eg, vomiting, diarrhea)
  5. Generalized (eg, anaphylactic shock).

    By definition, anaphylaxis is a life-threatening reaction that occurs on exposure to an allergen and involves acute respiratory distress, cardiovascular failure, or involvement of two or more organ systems.4

The blood tests for allergic disease are immunoassays that measure the level of IgE specific to a specific allergen. The tests can be used to assess sensitivity to various allergens, for example, to common inhalants such as dust mites and pollens and to foods, drugs, venom, and latex.

Types of immunoassays include enzyme-linked immunosorbent assays (ELISAs), fluorescent enzyme immunoassays (FEIAs), and radioallergosorbent assays (RASTs).

At present, most commercial laboratories use one of three autoanalyzer systems to measure specific IgE:

  1. ImmunoCAP (Phadia AB, Uppsala, Sweden)
  2. Immulite (Siemens AG, Berlin, Germany)
  3. HYTEC (Hycor/Agilent, Garden Grove, CA).

These systems use a solid-phase polymer (cellulose or avidin) in which the antigen is embedded. The polymer also facilitates binding of IgE and, therefore, increases the sensitivity of the test.5 Specific IgE from the patient’s serum binds to the allergen embedded in the polymer, and then unbound antibodies are washed off.

Despite the term “RAST,” these systems do not use radiation.

A fluorescent antibody is added that binds to the patient’s IgE, and the quantity of IgE present is calculated from the quantity of fluorescence.6 Results are reported in kilounits of antibody per liter (kU/L) or nanograms per milliliter (ng/mL).5–7

In general, the sensitivity of these tests ranges from 60% to 95% and their specificity from 30% to 95%, with a concordance among diverse immunoassays of 75% to 90%.8

Levels of IgE for a specific allergen are also divided into semiquantitative classes, from class I to class V or VI. In general, class I and class II correlate with a low level of allergen sensitization and, often, with a low likelihood of a clinical reaction.

On the other hand, classes V and VI reflect higher degrees of sensitization and generally correlate with IgE-mediated clinical reactions upon allergen exposure.

The interpretation of a positive (ie, “nonzero”) test result must be individualized on the basis of clinical presentation and risk factors. A specialist can make an significant contribution by helping to interpret any positive test result or a negative test result that does not correlate with the patient’s history.

Allergy blood testing is convenient, since it involves only a standard blood draw.

In theory, allergy blood testing may be safer, since it does not expose the patient to any allergens.

On the other hand, numerous patients experience bruising from venipuncture performed for any reason: 16% in one survey.9 In another survey,10 adverse reactions of any type occurred in % of patients undergoing venipuncture but only in % of those undergoing allergy skin testing. Therefore, allergy blood testing may be most appropriate in situations in which a patient’s history suggests that he or she may be at risk of a systemic reaction from a traditional skin test or in cases in which skin testing is not possible (eg, extensive eczema).

Another advantage of allergy blood testing is that it is not affected by drugs such as antihistamines or tricyclic antidepressants that suppress the histamine response, which is a problem with skin testing.

Allergy blood testing may also be useful in patients on long-term glucocorticoid therapy, although the data conflict.

Prolonged oral glucocorticoid use is associated with a decrease in mast cell density and histamine content in the skin,11,12 although in one study a corticosteroid was found not to affect the results of skin-prick testing for allergy.13 Thus, allergy blood testing can be performed in patients who own severe eczema or dermatographism or who cannot safely suspend taking antihistamines or tricyclic antidepressants.

Itchy eyes, a congested nose, sneezing, wheezing and hives: these are symptoms of an allergic reaction caused when plants release pollen into the air, generally in the spring or drop. Numerous people use hay fever as a colloquial term for these seasonal allergies and the inflammation of the nose and airways.

But hay fever is a misnomer, said Dr.

Jordan Josephson, an ear, nose and throat doctor and sinus specialist at Lenox Hill Hospital in New York City.

«It is not an allergy to hay,» Josephson, author of the book «Sinus Relief Now» (Perigee Trade, ), told Live Science. «Rather, it is an allergy to weeds that pollinate.»

Doctors and researchers prefer the phrase allergic rhinitis to describe the condition. More than 50 million people experience some type of allergy each year, according to the Asthma and Allergy Foundation of America.

In , % of adults and % of children reported own allergic rhinitis symptoms, according to the Centers for Disease Control and Prevention (CDC). Worldwide, between 10 and 30% of people are affected by allergic rhinitis, Josephson said.

In , spring arrived early in some parts of the country and later in others, according to the National Phenology Network (NPN). Spring brings blooming plants and, for some, lots of sneezing, itchy, watery eyes and runny noses. According to NPN data, spring reared its head about two weeks early in areas of California, Nevada and numerous of the Southern and Southeastern states.

Much of California, for example, is preparing for a brutal allergy season due to the large quantity of winter rain. On the other hand, spring ranged from about one to two weeks tardy in the Northwest, the Midwest and the Mid-Atlantic U.S. [Watch a Massive ‘Pollen Cloud’ Explode from Late-Blooming Tree]


Risk factors for allergy can be placed in two general categories, namely host and environmental factors.[31] Host factors include heredity, sex, race, and age, with heredity being by far the most significant. However, there own been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone.

Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.[32]


Main article: Food allergy

A wide variety of foods can cause allergic reactions, but 90% of allergic responses to foods are caused by cow’s milk, soy, eggs, wheat, peanuts, tree nuts, fish, and shellfish.[33] Other food allergies, affecting less than 1 person per 10, population, may be considered «rare».[34] The use of hydrolysed milk baby formula versus standard milk baby formula does not appear to change the risk.[35]

The most common food allergy in the US population is a sensitivity to crustacea.[34] Although peanut allergies are notorious for their severity, peanut allergies are not the most common food allergy in adults or children.

Severe or life-threatening reactions may be triggered by other allergens, and are more common when combined with asthma.[33]

Rates of allergies differ between adults and children. Peanut allergies can sometimes be outgrown by children. Egg allergies affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5.[36] The sensitivity is generally to proteins in the white, rather than the yolk.[37]

Milk-protein allergies are most common in children.[38] Approximately 60% of milk-protein reactions are immunoglobulin E-mediated, with the remaining generally attributable to inflammation of the colon.[39] Some people are unable to tolerate milk from goats or sheep as well as from cows, and numerous are also unable to tolerate dairy products such as cheese.

Roughly 10% of children with a milk allergy will own a reaction to beef. Beef contains little amounts of proteins that are present in greater abundance in cow’s milk.[40]Lactose intolerance, a common reaction to milk, is not a form of allergy at every, but rather due to the absence of an enzyme in the digestive tract.

Those with tree nut allergies may be allergic to one or to numerous tree nuts, including pecans, pistachios, pine nuts, and walnuts.[37] Also seeds, including sesame seeds and poppy seeds, contain oils in which protein is present, which may elicit an allergic reaction.[37]

Allergens can be transferred from one food to another through genetic engineering; however genetic modification can also remove allergens.

Little research has been done on the natural variation of allergen concentrations in unmodified crops.[41][42]


Latex can trigger an IgE-mediated cutaneous, respiratory, and systemic reaction. The prevalence of latex allergy in the general population is believed to be less than one percent. In a hospital study, 1 in surgical patients ( percent) reported latex sensitivity, although the sensitivity among healthcare workers is higher, between seven and ten percent.

Researchers attribute this higher level to the exposure of healthcare workers to areas with significant airborne latex allergens, such as operating rooms, intensive-care units, and dental suites. These latex-rich environments may sensitize healthcare workers who regularly inhale allergenic proteins.[43]

The most prevalent response to latex is an allergic contact dermatitis, a delayed hypersensitive reaction appearing as dry, crusted lesions. This reaction generally lasts 48–96 hours. Sweating or rubbing the area under the glove aggravates the lesions, possibly leading to ulcerations.[43]Anaphylactic reactions happen most often in sensitive patients who own been exposed to a surgeon’s latex gloves during abdominal surgery, but other mucosal exposures, such as dental procedures, can also produce systemic reactions.[43]

Latex and banana sensitivity may cross-react.

Furthermore, those with latex allergy may also own sensitivities to avocado, kiwifruit, and chestnut.[44] These people often own perioral itching and local urticaria. Only occasionally own these food-induced allergies induced systemic responses. Researchers suspect that the cross-reactivity of latex with banana, avocado, kiwifruit, and chestnut occurs because latex proteins are structurally homologous with some other plant proteins.[43]


Main article: Drug allergy

See also: Adverse drug reaction and Drug eruption

About 10% of people report that they are allergic to penicillin; however, 90% turn out not to be.[45] Serious allergies only happen in about %.[45]


Allergic diseases are strongly familial: identical twins are likely to own the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in non-identical twins.[50] Allergic parents are more likely to own allergic children,[51] and those children’s allergies are likely to be more severe than those in children of non-allergic parents.

Some allergies, however, are not consistent along genealogies; parents who are allergic to peanuts may own children who are allergic to ragweed. It seems that the likelihood of developing allergies is inherited and related to an irregularity in the immune system, but the specific allergen is not.[51]

The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk.[52] Several studies own shown that IgE levels are highest in childhood and drop rapidly between the ages of 10 and 30 years.[52] The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under [53]

Overall, boys own a higher risk of developing allergies than girls,[51] although for some diseases, namely asthma in young adults, females are more likely to be affected.[54] These differences between the sexes tend to decrease in adulthood.[51]

Ethnicity may frolic a role in some allergies; however, racial factors own been hard to separate from environmental influences and changes due to migration.[51] It has been suggested that diverse genetic loci are responsible for asthma, to be specific, in people of European, Hispanic, Asian, and African origins.[55]


Chronic stress can aggravate allergic conditions.

This has been attributed to a T helper 2 (TH2)-predominant response driven by suppression of interleukin 12 by both the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. Stress management in highly susceptible individuals may improve symptoms.[63]

Hygiene hypothesis

Main article: Hygiene hypothesis

Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a TH2-mediated immune response. Numerous bacteria and viruses elicit a TH1-mediated immune response, which down-regulates TH2 responses.

The first proposed mechanism of action of the hygiene hypothesis was that insufficient stimulation of the TH1 arm of the immune system leads to an overactive TH2 arm, which in turn leads to allergic disease.[56] In other words, individuals living in too sterile an environment are not exposed to enough pathogens to hold the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when they are not exposed to this level, the immune system will attack harmless antigens and thus normally benign microbial objects—like pollen—will trigger an immune response.[57]

The hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were, it is presumed, exposed to more infectious agents through their siblings, than in children from families with only one kid.

The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an significant theoretical framework for the study of allergic disorders. It is used to explain the increase in allergic diseases that own been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as significant modulators of immune system development, along with infectious agents.

Epidemiological data support the hygiene hypothesis. Studies own shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world.[58] Longitudinal studies in the third world protest an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner.[59] The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.[60] The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by Caesarean section rather than vaginal birth.[61][62]

Insect stings

Main article: Insect sting allergy

Typically, insects which generate allergic responses are either stinging insects (wasps, bees, hornets and ants) or biting insects (mosquitoes, ticks).

Stinging insects inject venom into their victims, whilst biting insects normally introduce anti-coagulants.

What is the difference between an allergy side effect and sensitivity to a medication

Toxins interacting with proteins

Another non-food protein reaction, urushiol-induced contact dermatitis, originates after contact with poison ivy, eastern poison oak, western poison oak, or poison sumac. Urushiol, which is not itself a protein, acts as a hapten and chemically reacts with, binds to, and changes the shape of integral membrane proteins on exposed skin cells. The immune system does not recognize the affected cells as normal parts of the body, causing a T-cell-mediated immune response.[46] Of these poisonous plants, sumac is the most virulent.[47] The resulting dermatological response to the reaction between urushiol and membrane proteins includes redness, swelling, papules, vesicles, blisters, and streaking.[48]

Estimates vary on the percentage of the population that will own an immune system response.

Approximately 25 percent of the population will own a strong allergic response to urushiol. In general, approximately 80 percent to 90 percent of adults will develop a rash if they are exposed to milligrams (×10−5gr) of purified urushiol, but some people are so sensitive that it takes only a molecular trace on the skin to initiate an allergic reaction.[49]

Other environmental factors

There are differences between countries in the number of individuals within a population having allergies. Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined.[64] Historically, the trees planted in urban areas were predominantly male to prevent litter from seeds and fruits, but the high ratio of male trees causes high pollen counts.[65]

Alterations in exposure to microorganisms is another plausible explanation, at present, for the increase in atopic allergy.[32] Endotoxin exposure reduces release of inflammatory cytokines such as TNF-α, IFNγ, interleukin, and interleukin from white blood cells (leukocytes) that circulate in the blood.[66] Certain microbe-sensing proteins, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes.[67]

Gutworms and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine chlorination and purification of drinking water supplies.[68] Recent research has shown that some common parasites, such as intestinal worms (e.g., hookworms), secrete chemicals into the gut wall (and, hence, the bloodstream) that suppress the immune system and prevent the body from attacking the parasite.[69] This gives rise to a new slant on the hygiene hypothesis theory—that co-evolution of humans and parasites has led to an immune system that functions correctly only in the presence of the parasites.

What is the difference between an allergy side effect and sensitivity to a medication

Without them, the immune system becomes unbalanced and oversensitive.[70] In specific, research suggests that allergies may coincide with the delayed establishment of gut flora in infants.[71] However, the research to support this theory is conflicting, with some studies performed in China and Ethiopia showing an increase in allergy in people infected with intestinal worms.[64] Clinical trials own been initiated to test the effectiveness of certain worms in treating some allergies.[72] It may be that the term ‘parasite’ could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work.[72] For more information on this topic, see Helminthic therapy.


Further information: Allergy prevention in children

Giving peanut products early may decrease the risk allergies while only breastfeeding during at least the first few months of life may decrease the risk of dermatitis.[92][93] There is no excellent evidence that a mother’s diet during pregnancy or breastfeeding affects the risk.[92] Nor is there evidence that delayed introduction of certain foods is useful.[92] Early exposure to potential allergens may actually be protective.[6]

Fish oil supplementation during pregnancy is associated with a lower risk.[93] Probiotic supplements during pregnancy or infancy may assist to prevent atopic dermatitis.[94][95]

Signs and symptoms

Affected organ Common signs and symptoms
Nose Swelling of the nasal mucosa (allergic rhinitis) runny nose, sneezing
Sinuses Allergic sinusitis
Eyes Redness and itching of the conjunctiva (allergic conjunctivitis, watery)
Airways Sneezing, coughing, bronchoconstriction, wheezing and dyspnea, sometimes outright attacks of asthma, in severe cases the airway constricts due to swelling known as laryngeal edema
Ears Feeling of fullness, possibly pain, and impaired hearing due to the lack of eustachian tube drainage.

What is the difference between an allergy side effect and sensitivity to a medication

Skin Rashes, such as eczema and hives (urticaria)
Gastrointestinal tract Abdominal pain, bloating, vomiting, diarrhea

Many allergens such as dust or pollen are airborne particles. In these cases, symptoms arise in areas in contact with air, such as eyes, nose, and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, itching, and redness of the eyes.[21] Inhaled allergens can also lead to increased production of mucus in the lungs, shortness of breath, coughing, and wheezing.[22]

Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications love aspirin and antibiotics such as penicillin.

Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhea, itchy skin, and swelling of the skin during hives. Food allergies rarely cause respiratory (asthmatic) reactions, or rhinitis.[23] Insect stings, food, antibiotics, and certain medicines may produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including the digestive system, the respiratory system, and the circulatory system.[24][25][26] Depending on the rate of severity, anaphylaxis can include skin reactions, bronchoconstriction, swelling, low blood pressure, coma, and death.

This type of reaction can be triggered suddenly, or the onset can be delayed. The nature of anaphylaxis is such that the reaction can seem to be subsiding, but may recur throughout a period of time.[26]


Substances that come into contact with the skin, such as latex, are also common causes of allergic reactions, known as contact dermatitis or eczema.[27] Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a «weal and flare» reaction characteristic of hives and angioedema.[28]

With insect stings a large local reaction may happen (an area of skin redness greater than 10cm in size).[29] It can final one to two days.[29] This reaction may also happen after immunotherapy.[30]


Management of allergies typically involves avoiding what triggers the allergy and medications to improve the symptoms.[7]Allergen immunotherapy may be useful for some types of allergies.[7]


Several medications may be used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes.

These include antihistamines, glucocorticoids, epinephrine (adrenaline), mast cell stabilizers, and antileukotriene agents are common treatments of allergic diseases.[96]Anti-cholinergics, decongestants, and other compounds thought to impair eosinophilchemotaxis, are also commonly used. Although rare, the severity of anaphylaxis often requires epinephrine injection, and where medical care is unavailable, a device known as an epinephrine autoinjector may be used.[26]


Main article: Allergen immunotherapy

Allergen immunotherapy is useful for environmental allergies, allergies to insect bites, and asthma.[7][97] Its benefit for food allergies is unclear and thus not recommended.[7] Immunotherapy involves exposing people to larger and larger amounts of allergen in an effort to change the immune system’s response.[7]

Meta-analyses own found that injections of allergens under the skin is effective in the treatment in allergic rhinitis in children[98][99] and in asthma.[97] The benefits may final for years after treatment is stopped.[] It is generally safe and effective for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insects.[]

The evidence also supports the use of sublingual immunotherapy for rhinitis and asthma but it is less strong.[] For seasonal allergies the benefit is small.[] In this form the allergen is given under the tongue and people often prefer it to injections.[] Immunotherapy is not recommended as a stand-alone treatment for asthma.[]

Alternative medicine

An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective.[] EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to reply by favoring desensitization, or down-regulation, rather than sensitization.

EPD has also been tried for the treatment of autoimmune diseases but evidence does not show effectiveness.[]

A review found no effectiveness of homeopathic treatments and no difference compared with placebo. The authors concluded that, based on rigorous clinical trials of every types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of homeopathic treatments.[]

According to the National Middle for Complementary and Integrative Health, U.S, the evidence is relatively strong that saline nasal irrigation and butterbur are effective, when compared to other alternative medicine treatments, for which the scientific evidence is feeble, negative, or nonexistent, such as honey, acupuncture, omega 3’s, probiotics, astragalus, capsaicin, grape seed extract, Pycnogenol, quercetin, spirulina, stinging nettle, tinospora or guduchi.



Acute response

In the early stages of allergy, a type I hypersensitivity reaction against an allergen encountered for the first time and presented by a professional antigen-presenting cell causes a response in a type of immune cell called a TH2 lymphocyte; a subset of T cells that produce a cytokine called interleukin-4 (IL-4). These TH2 cells interact with other lymphocytes called B cells, whose role is production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to start production of a large quantity of a specific type of antibody known as IgE.

Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a helpful of Fc receptor called FcεRI) on the surface of other kinds of immune cells called mast cells and basophils, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage, are sensitized to the allergen.[32]

If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complicated interacts with the same allergenic molecule, and activates the sensitized cell.

Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation, and smooth muscle contraction. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis.

Depending on the individual, allergen, and mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to specific body systems; asthma is localized to the respiratory system and eczema is localized to the dermis.[32]

Late-phase response

After the chemical mediators of the acute response subside, late-phase responses can often happen. This is due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils and macrophages to the initial site. The reaction is generally seen 2–24 hours after the original reaction.[73] Cytokines from mast cells may frolic a role in the persistence of long-term effects.

Late-phase responses seen in asthma are slightly diverse from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils and are still dependent on activity of TH2 cells.[74]

Allergic contact dermatitis

Although allergic contact dermatitis is termed an «allergic» reaction (which generally refers to type I hypersensitivity), its pathophysiology actually involves a reaction that more correctly corresponds to a type IV hypersensitivity reaction.[75] In type IV hypersensitivity, there is activation of certain types of T cells (CD8+) that destroy target cells on contact, as well as activated macrophages that produce hydrolyticenzymes.