Immediate Hypersensitivity Reactions Clinical Presentation

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 (eg, drug administration, insect sting, food ingestion, allergen immunotherapy) but can 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 (eg, first reaction to insect sting) or because they were unaware of exposure to the allergen (eg, 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 be obtained. If applicable, a food history should also be obtained. Exercise-induced anaphylaxis may be associated with prior ingestion of a food (eg, wheat, peanut, tree nuts, celery) or drug (eg, NSAID) that does not produce symptoms when ingested without subsequent exercise.^[28]
• 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.
  • Repeated exposure to the allergen can result in chronic allergic inflammation, which causes chronic nasal congestion that can be further complicated by sinusitis.
• Allergic asthma

  • Allergen exposure results in bronchoconstriction, and patients may report shortness of breath (eg, difficulty getting air out), wheezing, cough, and/or chest tightness.
  • Long-term allergen exposure can cause chronic changes of increased difficulty breathing and chest tightness, and the patient may give a history of repeated rescue inhaler use or reduced peak flows.
• 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.
  • Acute urticaria (lasting < 6 wk) can be caused by viral infections, foods, drugs, or contact allergens.
  • Chronic urticaria lasts longer than 6 weeks. Although many causes are possible, often, a cause is not found. In many cases, this is not due to antigen-IgE – mediated immediate hypersensitivity but to an autoantibody to the high affinity IgE receptor or to IgE itself.
  • 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 allergen exposure, especially food allergies, in some patients.
  • Patients report significant pruritus that causes scratching, which produces 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 (eg, lactose intolerance) commonly cause these symptoms.
  • Eosinophilic esophagitis and gastritis are newly recognized syndromes that may be allergic in nature.

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%.
  • 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.
  • Patients may be wheezing during the respiratory examination, which is secondary to bronchoconstriction.
  • Confusion and alteration of mental status can occur.
• Allergic rhinoconjunctivitis

  • Patients may sneeze, be congested, have a runny nose, or have frequent throat clearing and/or cough from postnasal drip.
  • Sclera may be injected, and patients may have dark rings under the eyes (ie, allergic shiners).
  • Nasal mucosa can be boggy and pale, usually with clear drainage.
  • 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 might not be heard in patients with milder symptoms or, if the asthma is very severe, patients may not move enough air to produce wheezing.
  • Breaths may be shallow or the patient may have a prolonged expiratory phase.
  • Cyanosis of the lips, fingers, or toes (caused by hypoxemia) may occur with severe asthma.
• Urticaria/angioedema

  • Urticaria 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 and may leave postinflammatory hyperpigmentation upon healing.
  • Angioedema is localized swelling of the soft tissues that can occur anywhere but is particularly concerning if pharyngeal or laryngeal tissues are involved.
• 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, crusted lesions.
  • In infants, the head and extensor surfaces are more involved, whereas in older children and adults, the flexural surfaces tend to be affected.

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. Mutations of specific alleles on the long arm of chromosome 5 have been associated with higher levels of IL-4 and IgE and are known as IL-4 promoter polymorphisms.^[29] Impaired function of Treg cells may also contribute to the development of atopic diseases.^[30]

Environmental issues 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 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 (eg, pollen, animal dander), drugs, 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.
  • 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. Note that all drug hypersensitivity reactions are not mediated by IgE. In addition to anaphylactoid reactions, drug reactions can be caused by cytotoxicity and immune-complex formation and by other immunopathologic mechanisms.
• Foods

  • The most common food allergens are peanuts, tree nuts, finned fish, shellfish, eggs, milk, soy, and wheat.
  • Certain foods can cross-react with latex allergens. These foods include banana, kiwi, chestnut, avocado, pineapple, passion fruit, apricot, and grape.
• Hymenoptera

  • 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.
  • At least 50 Americans die each year from anaphylaxis caused by a stinging insect.
• Anaphylactoid 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 dye, opiates, and vancomycin (eg, red man syndrome).
  • Patients can be pretreated with glucocorticosteroids and both H1 and H2 antihistamines prior to exposure to iodinated radiocontrast dye. This, together with the use of low-osmolal nonionic dye, reduces the risk of a repeat reaction to approximately 1%.
  • 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, urticaria, or angioedema after ingestion. 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.