History
History findings vary depending on which organ systems are affected.
Anaphylaxis
Patients may report skin itching, localized or diffuse pruritus, dizziness, faintness, and diaphoresis. Difficulty breathing can result from angioedema of the pharyngeal tissue, from bronchoconstriction, or from both. Patients may also report GI symptoms, including nausea, vomiting, diarrhea, and abdominal cramping. Patients may experience uterine cramping or urinary urgency. Patients can have a sudden onset of respiratory and/or circulatory collapse and go into anaphylactic shock.
Symptoms usually begin within minutes of allergen exposure (e.g., drug administration, insect sting, food ingestion, allergen immunotherapy), but symptoms may start up to two hours after exposure. Symptoms can also recur hours after the initial exposure (late-phase reaction).
Patients may not be able to identify the allergen either because they are unaware of the allergy (e.g., first reaction to insect sting) or because they were unaware of exposure to the allergen (e.g., a patient who is allergic to peanuts who eats a processed food containing hidden peanut protein).
Particular attention should be given to new or recently changed medications. A history specific for insect stings or new environmental exposures should also be obtained. If applicable, a food history should also be obtained. Exercise-induced anaphylaxis may be associated with prior ingestion of a food (e.g., wheat, peanut, tree nuts, fish, celery) and/or drug (e.g., NSAID) that does not produce symptoms when ingested without subsequent exercise. [30]
Allergic rhinoconjunctivitis
Symptoms consist of congestion; sneezing; itchy, runny nose and eyes; and itching of the palate and inner ear. Patients may also report postnasal drip, which can cause sore throat, coughing, or throat clearing.
Rhinoconjunctivitis usually results from exposure to aeroallergens and can be seasonal or perennial. Airborne allergens typically also cause ocular symptoms consisting of itchy eyes, tearing, swelling or redness of the eyes. Worrisome ocular symptoms include photophobia, pain, and/or change in vision where the diagnoses of atopic keratoconjunctivitis or vernal keratoconjunctivitis should be entertained.
Repeated exposure to the allergen can result in chronic allergic inflammation, which causes chronic nasal congestion that can be further complicated by sinusitis.
An important piece of the history also includes whether symptoms are improved or abated with the use of allergy medications and/or with allergen avoidance.
Allergic asthma
In 2007, the National Asthma Education and Prevention Program (NAEPP) Expert Panel from the National Heart, Lung, and Blood Institute (NHLBI) released guidelines on the diagnosis and management of asthma. The classification of an asthmatic depends on the age of the patient (ages 0-4 years of age, 5-11 years of age, and 12 years and older). [31]
Asthmatics are classified into 4 groups: intermittent, mild persistent, moderate persistent, and severe persistent. [31] Each classification is based on severity. Severity is classified by risk (exacerbations requiring oral systemic corticosteroids) and impairment (symptoms, nighttime awakenings, interference with normal activity, short-acting beta2-agonist use [not for premedication before exercise], and lung function if able to perform spirometry). [31] These symptoms are assessed each visit to make medical decisions to change or continue current medical therapy.
Acute allergen exposure can result in bronchoconstriction, and patients may report shortness of breath (e.g., difficulty getting air out), wheezing, cough, and/or chest tightness around the time of exposure. Long-term allergen exposure can cause chronic airway changes and the patient may give a history of repeated rescue inhaler use.
Urticaria/angioedema
Diffuse hives or wheals may occur and cause significant pruritus; individual wheals resolve after minutes to hours, but new wheals can continue to form. Urticaria lesions don't typically last longer than 24 hours in one location.
Acute urticaria (lasting < 6 wks) can be caused by viral infections, foods, drugs, stinging insects, or contact allergens.
Chronic urticaria lasts longer than 6 weeks. Although many causes are possible, often a cause is not found. In many cases, the etiology is termed idiopathic.
Angioedema is localized tissue swelling that can occur in soft tissues throughout the body. Patients may report pain at the site of swelling instead of pruritus, which occurs with urticaria.
Angioedema of the laryngopharynx can obstruct the airway, and patients may report difficulty breathing. Stridor or hoarseness may be present. Angioedema of the laryngopharynx can be life threatening.
Atopic dermatitis
This condition is an eczematous cutaneous eruption more common in children than in adults; it can be exacerbated by food and/or environmental allergen exposure in some patients.
Patients report significant pruritus that causes scratching, which exacerbates the lesions. Superinfection with staphylococcal organisms can occur, particularly in severely excoriated or cracked lesions.
GI allergies
Patients may report nausea, vomiting, abdominal cramping, and diarrhea after ingestion of the offending food. Note that other mechanisms (e.g., lactose intolerance) commonly cause these symptoms, but eosinophilic gastroenteritides should also be considered in persons with predominant GI symptoms.
Physical
Physical examination findings vary with the organ system involved.
Anaphylaxis
Vital signs should be monitored closely because patients can quickly progress to circulatory and/or respiratory failure. Tachycardia may precede hypotension. Patients who are hypotensive may have reflex tachycardia, but bradycardia can also occur in 5% of cases.
Patients may have urticaria, angioedema, or both. Angioedema of the airway and throat can result in respiratory failure or asphyxiation; therefore, this dangerous occurrence must be closely monitored. Around 90% of cases of anaphylaxis have cutaneous manifestations, but the absence of them doesn't exclude anaphylaxis as being considered in the differential diagnosis.
Patients may be wheezing during the respiratory examination, which is secondary to bronchoconstriction.
Confusion and alteration of mental status can occur.
Patients may have abdominal cramping, nausea, vomiting and/or diarrhea as well as urinary urgency.
Female patients may have uterine cramping.
Allergic rhinoconjunctivitis
Patients may sneeze, be congested, have a runny nose, or have frequent throat clearing and/or cough from postnasal drip.
Patients may have a horizontal line right below the nasal bridge (i.e., allergic salute) from repeated upward itching of the nose.
Sclera may be injected, and patients may have dark rings under the eyes (i.e., allergic shiners).
Nasal mucosa can be boggy and pale, usually with clear drainage. Some patients may exhibit mouth breathing due to severe obstructive allergic edema in nasopharynx.
The pharynx may have a cobblestone appearance reflecting lymphoid hyperplasia from postnasal mucus drainage.
The patient may have frontal or maxillary sinus tenderness from chronic sinus congestion or infection.
Allergic asthma
Findings can vary depending on the patient and the severity of symptoms. Patients may be coughing or appear short of breath. Wheezing may be present, but it always present in asthmatics. Some patients may not be able to move enough air to produce wheezing (i.e., silent chest), which can be a worrisome sign of impending respiratory failure.
Breaths may be shallow or the patient may have a prolonged expiratory phase.
Cyanosis of the lips, fingers, or toes (caused by hypoxemia) may also occur.
Urticaria/angioedema
Urticaria occurs in the dermis of the skin from increased vascular permeability from the action of vasoactive substances released from mast cells and basophils. [8] It is usually represented by wheals with surrounding erythema. Wheals from allergic causes usually last a few minutes to a few hours. Wheals due to cutaneous vasculitis may last more than 24 hours, may be painful, and may leave postinflammatory hyperpigmentation upon healing.
Angioedema is localized swelling of the deep dermis, subcutaneous or submucosal tissue secondary to vascular leak. Sites of angioedema are typically the lips, tongue, pharynx, cheeks, eyes, hands and feet, penis and scrotum, and/or bowel wall. If laryngeal edema is present, a diagnosis of idiopathic anaphylaxis should be entertained.
Atopic dermatitis
The physical examination findings can vary with the severity of the disease. In less severe cases, skin can appear normal, dry, or with erythematous papules. In more severe cases, patients can have extremely dry, lichenified, cracked, and, sometimes have crusted lesions.
In infants, the head and extensor surfaces are more involved, whereas in older children and adults, the flexural surfaces tend to be more affected.
Causes
Atopic conditions
Genetics
Atopy is defined as the genetic predisposition to form IgE antibodies in response to exposure to allergens. Therefore, a genetic predisposition exists for the development of atopic diseases. Common allergic diseases are typically complex genetic disorders, as not one affected gene confers disease; but mutations or single nucleotide polymorphisms in identified at-risk genes may contribute to disease development and phenotype. Atopic conditions, such as asthma and atopic dermatitis, have been studied extensively and numerous candidate susceptibility genes are being uncovered at a rapid rate. [81] For example, a mutation in the gene encoding the filaggrin protein confers an increased risk for the development of atopic dermatitis. [82] Furthermore, the role of genetics in pharmacology is expanding as evidenced by specific mutations in the gene encoding the beta-2-receptor, which may decrease a patient's ability to respond to albuterol for asthma symptom relief. [83] Finally, family studies have demonstrated a heritability component in atopic conditions. [84]
Environment
Environmental factors also play an important role, although the role that exposure at an early age to certain antigens might play in either the progression to or the protection from the development of an allergic response still remains unclear. Some studies have shown that children in day care and those with older siblings may be less likely to develop allergic disease. The environment certainly can help determine the allergens to which the patient will be exposed. For example, children in inner cities are more likely to be sensitized to cockroaches than are children in suburban or rural areas. Similarly, dust mites, a potent allergen, are primarily found in humid climates, and those who have never been exposed to such a climate are less likely to be allergic to mites.
Allergic reactions
Reactions can be elicited by various aeroallergens (e.g., pollen, mold, animal dander) or insect stings.
Other possible causes are latex, drug, and food allergy.
Allergens
Allergens can be complete protein antigens or low–molecular-weight proteins capable of eliciting an IgE response. It is rare when a carbohydrate moiety induces IgE production (i.e., alpha-gal allergy or mammalian meat allergy).
Pollen and animal dander represent complete protein antigens.
Haptens are low-molecular-weight (inorganic) antigens that are not capable of eliciting an allergic response by themselves. They must bind to serum or tissue proteins in order to elicit a response. This is a typical cause of drug hypersensitivity reactions, with IgE-mediated penicillin drug allergy as the prototypic case. Furthermore, antibiotics (like β-lactams) are the most common drugs to induce IgE-mediated reactions, but this can happen with a wide array of other periooperative medications and platinum-based chemotherapeutics. [87] Note that all drug hypersensitivity reactions are not mediated by IgE. [87] In addition to non-IgE-mediated reactions, drug reactions can be caused by cytotoxicity and immune-complex formation and by other immunopathologic mechanisms. [87]
Foods
The most common allergens in IgE-mediated food allergy are peanuts, tree nuts, finned fish, shellfish, eggs, milk, soy, and wheat. Sesame seed is also a food allergen that is highly allergenic and is becoming more widely recognized as such. [73]
Certain foods can cross-react with latex allergens. These foods include banana, kiwi, chestnut, avocado, pineapple, passion fruit, apricot, and grape.
Fresh fruits and vegetables as well as peanut and some tree nuts can induce pollen-food allergy syndrome (PFAS) in individuals who have IgE to common aeroallergens. PFAS is an IgE-mediated food allergy with symptoms typically limited to the oropharynx, but a small portion can have anaphylactic reactions to the offending foods. Cooking the fresh fruits and vegetables to change the conformation of the cross-reactive protein allows affected individuals the ability to consume cooked forms of the food while avoiding the raw forms. This is not the case with nuts, so complete avoidance of these foods is warranted.
Hymenoptera
Honey bee, wasp, yellow jacket, hornet, and fire ant stings can cause IgE-mediated reactions.
While anaphylaxis is the most serious reaction, localized swelling and inflammation can also occur and do not by themselves indicate increased risk of a subsequent life-threatening reaction.
Potentially life-threatening hypersensitivity reactions to insect stings are estimated in 0.4 to 0.8% of children and 3% of adults. [75] At least 40 Americans die each year from anaphylaxis caused by a stinging insect. [74]
Non-IgE-mediated reactions
Non–IgE-mediated mast cell and basophil degranulation can occur from a variety of substances. Although the mechanisms are different, the clinical manifestations can appear the same.
Causes can include radiocontrast medium, opiates, and vancomycin (e.g., red man syndrome).
Patients can be pretreated with glucocorticosteroids and both H1 and H2 antihistamines prior to exposure to radiocontrast media. This, together with the use of low-osmolar or iso-osmolar nonionic dye which reduces the risk of a repeat reaction. Furthermore, reported radiocontrast media-adverse drug reactions are not related to iodine, so a radiocontrast media allergy should not be listed as an iodine allergy.
Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) can also cause reactions by causing release of leukotrienes via the 5-lipoxygenase pathway of arachidonic acid metabolism. Patients susceptible to this syndrome can develop acute asthma exacerbation, nasal congestion, profuse rhinorrhea, ocular itching/injection, skin erythema, angioedema, and even life-threatening anaphylaxis with hypotension and shock after ingestion. [8] However, note that in rare cases, patients can have what are thought to be true IgE-mediated anaphylactic reactions to a specific NSAID. In these cases, no cross-reactivity occurs with other NSAIDs.
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Immediate hypersensitivity reactions. Sensitization phase of an immunoglobulin E–mediated allergic reaction.
Tables
Age |
Step 1 |
Step 2 |
Step 3 |
Step 4 |
Step 5 |
Step 6 |
0-4 years |
SABA PRN |
Low-dose ICS |
Medium-dose ICS |
Medium-dose ICS plus LABA or montelukast |
High-dose ICS plus LABA or montelukast |
High-dose ICS plus LABA or montelukast and oral corticosteroids |
5-11 years |
SABA PRN |
Low-dose ICS |
Low-dose ICS plus LABA or LTRA or theophylline |
Medium-dose ICS plus LABA |
High-dose ICS plus LABA |
High-dose ICS plus LABA plus oral corticosteroids |
12 years or older |
SABA PRN |
Low-dose ICS |
Low-dose ICS plus LABA or medium-dose ICS |
Medium-dose ICS plus LABA |
High-dose ICS plus LABA |
High-dose ICS plus LABA plus oral corticosteroids |
